新型嘧啶并环分子的设计与合成
|
摘要
本论文论述了两类具有特权结构的新型嘧啶并环分子库的设计与合成分为三章。
第一章介绍了背景材料和总结本实验室合成嘧啶并环化合物的研究工作,引出了本论文的目的和意义。
第二章中,首次开发了以Bischler-Napieralski反应为关键关环步骤构建嘧啶并[4,5-b][1,4]苯并硫氮(艹卓)分子骨架的方法,并在此基础上探索其衍生物库的制备。
第三章作为第二章的延续,开发了应用嘧啶并[4,5-b][1,4]苯并硫氮(艹卓)的一氧化硫挤出反应合成嘧啶并[5,4-c]异喹啉骨架的方法,并且通过三条路线分别构建了结构多样化的化合物库。
The dissertation is divided into three chapters.In Chapter One,the application of privileged structures and pyrimidine-fused heterocyclic scaffolds in drug design were summarized.
Discovery of lead compound was the beginning and key step in drug design. Design and synthesis of structurally diverse libraries based on privileged structures were an efficient way to discover lead compounds.Pyrimidine and pyrimidine-fused heterocyclic compounds have been widely employed in design of privileged structures in medicinal chemistry.Moreover,benzothiazepine and isoquinoline derivatives are well-known to exhibit diverse biological activities. Bischler-Napieralski reaction was an efficient method to synthesize nitrogen containing heterocyclic compounds and has been used to prepare benzothiazepine derivatives.The aim and significance of the dissertation were to design and synthesize pyrimido[4,5-b][1,4]benzothiazepine and pyrimido[5,4-c]isoquinoline scaffolds with potential applications in drug discovery.
In Chapter Two,an efficient methodology to access to libraries of pyrimido[4,5-b][1,4]benzothiazepine scaffold via Bischler-Napieralski reaction was firstly developed.
Four 5-amino-4,6-bisphenylthiopyrimidins were prepared by thiophenol substitution of the commercially available 5-amino-4,6-dichloro-pyrimidine. Then the precursors were treated with eight carboxylic acids or their derivatives under the catalysis of PPA/POCl_3 to lead to twenty pyrimido[4,5-b][1,4]benzothiazepine derivatives with 30%-98%yields.The results shown that the cyclization is suitable for various substrates.The isolation and characterization of intermediates supported that the cyclization may be mechanistically similar to the Bischler-Napieralski reaction.In addition,the selective oxidation of 4-arylthio groups to the corresponding sulfoxide compound with 75%-77%yields,which were converted to corresponding 4-n-butylamino-substituted pyrimido[4,5-b][1,4]benzothiazepines via nucleophilic substitution with 80%-90%yields.The above results provided an efficient methodology to access structurally diverse libraries of pyrimido[4,5-b][1,4]benzothiazepines.Finally,it was proved that the cyclization is unsuitable to prepare 8 or 9-membered heterocycles.
To expand the scope of applications,an efficient strategies to access to structurally diverse libraries of pyrimido[5,4-c]isoquinolines via sulfur monoxide extrusion reaction were developed in Chapter Three.
The scope of the sulfur extrusion reaction of pyrimido[4,5-b][1,4]benzothiazepines was investigated.The pyrimidobenzothiazepine sulfoxides were subjected to the thermal sulfur monoxide extrusion reaction,but no sulfur extrusions were observed for sulfide and sulfone analogues.Then the selective sequential oxidation of 4-arylthiopyrimido[4,5-b][1,4]benzothiazepines were investigated. 4-Arylsulfonylpyrimido[4,5-b][1,4]benzothiazepine sulfoxides were prepared with 52%-60%yields.The nucleophilic substitution of side-chain sulfone by n-butylamine afforded 4-aminopyrimido[4,5-b][1,4]benzothiazepine sulfoxides with 85%-92%yields,which were converted to the final 4-aminopyrimido[5,4-c]isoquinolines via thermal sulfur monoxide extrusion with high yields(80%-92%).The above results provided an efficient methodology to prepare libraries of pyrimido[5,4-c]isoquinoline with more diversities.
Moreover,three approaches to access structurally diverse libraries of pyrimido[5,4-c]isoquinolines were developed.In the first,a one-pot procedure to prepare pyrimido[5,4-c]isoquinolines by combining the nucleophilic replacement and sulfoxide extrusion was explored.Various nucleophiles were readily introduced via the displacement of the 4-arylsulfonyl groups thereby generating additional structural diversification,but the reactions involving weak nucleophiles were more difficult.In the second, 4-arylsulfonylpyrimido[4,5-b][1,4]benzothiazepine sulfoxides were treated with ring sulfoxide extrusion and eventual nucleophilic substitution of the side-chain sulfone group to the desired pyrimido[5,4-c]isoquinolines.The efficiency to prepare 6-arylpyrimido[5,4-c]isoquinolines with a weak nucleophiles substituent at the 4-position was improved.Twenty-eight 6-arylpyrimido[5,4-c]isoquinolines were prepared via the above two approaches.In the third,a 4-step procedure, pyrimido[4,5-b][1,4]benzothiazepines were first carefully oxidized to the side-chain sulfoxide analogs followed by its substitution by a nucleophile to provide 4-substituted pyrimido[4,5-b][1,4]benzothiazepines,then oxidized again to the ring sulfoxides followed by sulfoxide extrusion to give the desired pyrimido[5,4-c]isoquinolines.The last two steps of the transformation could be carried out in a continuous operation without purification of the ring sulfoxide analogs to afford thirteen pyrimidoisoquinolines.This procedure expands the synthesis to 6-alkylpyrimido[5,4-c]isoquinolines.The three approaches complement not only to each other,but also to previously reported procedures to generate pyrimido[5,4-c]isoquinoline libraries with high structural diversity of pharmaceutically interests.
第一章介绍了背景材料和总结本实验室合成嘧啶并环化合物的研究工作,引出了本论文的目的和意义。
第二章中,首次开发了以Bischler-Napieralski反应为关键关环步骤构建嘧啶并[4,5-b][1,4]苯并硫氮(艹卓)分子骨架的方法,并在此基础上探索其衍生物库的制备。
第三章作为第二章的延续,开发了应用嘧啶并[4,5-b][1,4]苯并硫氮(艹卓)的一氧化硫挤出反应合成嘧啶并[5,4-c]异喹啉骨架的方法,并且通过三条路线分别构建了结构多样化的化合物库。
The dissertation is divided into three chapters.In Chapter One,the application of privileged structures and pyrimidine-fused heterocyclic scaffolds in drug design were summarized.
Discovery of lead compound was the beginning and key step in drug design. Design and synthesis of structurally diverse libraries based on privileged structures were an efficient way to discover lead compounds.Pyrimidine and pyrimidine-fused heterocyclic compounds have been widely employed in design of privileged structures in medicinal chemistry.Moreover,benzothiazepine and isoquinoline derivatives are well-known to exhibit diverse biological activities. Bischler-Napieralski reaction was an efficient method to synthesize nitrogen containing heterocyclic compounds and has been used to prepare benzothiazepine derivatives.The aim and significance of the dissertation were to design and synthesize pyrimido[4,5-b][1,4]benzothiazepine and pyrimido[5,4-c]isoquinoline scaffolds with potential applications in drug discovery.
In Chapter Two,an efficient methodology to access to libraries of pyrimido[4,5-b][1,4]benzothiazepine scaffold via Bischler-Napieralski reaction was firstly developed.
Four 5-amino-4,6-bisphenylthiopyrimidins were prepared by thiophenol substitution of the commercially available 5-amino-4,6-dichloro-pyrimidine. Then the precursors were treated with eight carboxylic acids or their derivatives under the catalysis of PPA/POCl_3 to lead to twenty pyrimido[4,5-b][1,4]benzothiazepine derivatives with 30%-98%yields.The results shown that the cyclization is suitable for various substrates.The isolation and characterization of intermediates supported that the cyclization may be mechanistically similar to the Bischler-Napieralski reaction.In addition,the selective oxidation of 4-arylthio groups to the corresponding sulfoxide compound with 75%-77%yields,which were converted to corresponding 4-n-butylamino-substituted pyrimido[4,5-b][1,4]benzothiazepines via nucleophilic substitution with 80%-90%yields.The above results provided an efficient methodology to access structurally diverse libraries of pyrimido[4,5-b][1,4]benzothiazepines.Finally,it was proved that the cyclization is unsuitable to prepare 8 or 9-membered heterocycles.
To expand the scope of applications,an efficient strategies to access to structurally diverse libraries of pyrimido[5,4-c]isoquinolines via sulfur monoxide extrusion reaction were developed in Chapter Three.
The scope of the sulfur extrusion reaction of pyrimido[4,5-b][1,4]benzothiazepines was investigated.The pyrimidobenzothiazepine sulfoxides were subjected to the thermal sulfur monoxide extrusion reaction,but no sulfur extrusions were observed for sulfide and sulfone analogues.Then the selective sequential oxidation of 4-arylthiopyrimido[4,5-b][1,4]benzothiazepines were investigated. 4-Arylsulfonylpyrimido[4,5-b][1,4]benzothiazepine sulfoxides were prepared with 52%-60%yields.The nucleophilic substitution of side-chain sulfone by n-butylamine afforded 4-aminopyrimido[4,5-b][1,4]benzothiazepine sulfoxides with 85%-92%yields,which were converted to the final 4-aminopyrimido[5,4-c]isoquinolines via thermal sulfur monoxide extrusion with high yields(80%-92%).The above results provided an efficient methodology to prepare libraries of pyrimido[5,4-c]isoquinoline with more diversities.
Moreover,three approaches to access structurally diverse libraries of pyrimido[5,4-c]isoquinolines were developed.In the first,a one-pot procedure to prepare pyrimido[5,4-c]isoquinolines by combining the nucleophilic replacement and sulfoxide extrusion was explored.Various nucleophiles were readily introduced via the displacement of the 4-arylsulfonyl groups thereby generating additional structural diversification,but the reactions involving weak nucleophiles were more difficult.In the second, 4-arylsulfonylpyrimido[4,5-b][1,4]benzothiazepine sulfoxides were treated with ring sulfoxide extrusion and eventual nucleophilic substitution of the side-chain sulfone group to the desired pyrimido[5,4-c]isoquinolines.The efficiency to prepare 6-arylpyrimido[5,4-c]isoquinolines with a weak nucleophiles substituent at the 4-position was improved.Twenty-eight 6-arylpyrimido[5,4-c]isoquinolines were prepared via the above two approaches.In the third,a 4-step procedure, pyrimido[4,5-b][1,4]benzothiazepines were first carefully oxidized to the side-chain sulfoxide analogs followed by its substitution by a nucleophile to provide 4-substituted pyrimido[4,5-b][1,4]benzothiazepines,then oxidized again to the ring sulfoxides followed by sulfoxide extrusion to give the desired pyrimido[5,4-c]isoquinolines.The last two steps of the transformation could be carried out in a continuous operation without purification of the ring sulfoxide analogs to afford thirteen pyrimidoisoquinolines.This procedure expands the synthesis to 6-alkylpyrimido[5,4-c]isoquinolines.The three approaches complement not only to each other,but also to previously reported procedures to generate pyrimido[5,4-c]isoquinoline libraries with high structural diversity of pharmaceutically interests.
引文
1.王兰明.新药研究开发的途径与方法(上).中国药业.2000,9,11-13.
2.郭宗儒.药物分子设计.科学出版.2005.
3.仉文升,李安良.药物化学.北京:高等教育出版社.1999
4.Bohacek,R.S.;McMartin,C.;Guida,W.C.Methods for drug discovery:development of potent,selective,orally effective cholecystokinin antagonists.The art and practice of structure-based drug design:a molecular modeling perspective.Med.Res.Rev.1996,16,3-50.
5.Kolb,H.C.;Finn,M.G.;Sharpless,K.B.Click Chemistry:Diverse Chemical Function from a Few Good Reactions.Angew.Chem.Int.Ed.Engl.2001,40,2004-2021.
6.Evans,B.E.;Rittle,K.E.;Bock,M.G.;DiPardo,R.M.;Freidinger,R.M.;Whitter,W.L.;Lundell,G.F.;Veber,D.F.;Anderson,P.S.;Chang,R.S.L.;Lotti,V.J.;Cerino,D.J.;Chen,T.B.;Kling,P.J.;Kunkel,K.A.;Springer,J.P.;Hirshfield,J.Methods for drug discovery:development of potent,selective,orally effective cholecystokinin antagonists.J.Med.Chem.1988,31,2235-2246.
7.Ariens,E.J.;Beld,A.J.;Rodrigues de Miranda,J.F.;Simonis,A.M.In The Receptors A Comprehensive Treatise;O'Brien,R.D.,Ed.Plenum Press:New York,1979,33.
8.Andrews,P.R.;Lloyd,E.J.Molecular conformation and biological activity of central nervous system active drugs.Med.Res.Rev.1982,2,355-393.
9.Converso,A.;Burow,K.;Marzinzik,A.;Sharpless,K.B.;Finn,M.G.2,6-Dichloro-9-thiabicyclo[3.3.1]nonane:A Privileged,Bivalent Scaffold for the Display of Nucleophilic Components.J.Org.Chem.2001,66,4386-4392.
10.Hajduk,P.J.;Bures,M.;Praestgaard,J.;Fesik,S.W.Privileged Molecules for Protein Binding Identified from NMR-Based Screening.J.Med.Chem.2000,43,3443-3447.
11.Lowe,J.A.,Ⅲ;Hageman,D.L.;Drozda,S.E.;McLean,S.;Bryce,D.K.;Crawford,R.T.;Zorn,S.;Morrone,J.;Bordner,J.5-Phenyl-3-ureidobenzazepin-1-ones as Cholecystokinin-B Receptor Antagonists.J.Med.Chem.1994,3 7,3789-3811.
12.Matter,H.;Baringhaus,K.-H.;Naumann,T.;Klabunde,T.;Pirard,B.Computational Approaches Towards the Rational Design of Drug-like Compound Libraries.Comb.Chem.High Throughput Screen.2001,4,453-475.
13.Nicolaou,K.C.;Pfefferkorn,J.A.;Barluenga,S.;Mitchell,H.J.;Roecker,A.J.;Cao,G.-Q.Natural Product-like Combinatorial Libraries Based on Privileged Structures.3.The "Libraries from Libraries" Principle for Diversity Enhancement of Benzopyran Libraries.J.Am.Chem.Soc.2000,122,9968-9976.
14.Nicolaou,K.C.;Pfefferkorn,J.A.;Mitchell,H.J.;Roecker,A.J.;Barluenga,S.;Cao,G.-Q.;Affleck,R.L.;Lillig,J.E.Natural Product-like Combinatorial Libraries Based on Privileged Structures.2.Construction of a 10000-Membered Benzopyran Library by Directed Split-and-Pool Chemistry Using NanoKans and Optical Encoding.J.Am.Chem.Soc.2000,122,9954-9967.
15.Smith,A.B.,Ⅲ;Favor,D.A.;Sprengeler,P.A.;Guzman,M.C.;Carroll,P.J.;Furst,G.T.;Hirschmann,R.Molecular modeling,synthesis,and structures of N-methylated 3,5-linked pyrrolin-4-ones toward the creation of a privileged nonpeptide scaffold.Bioorg.Med.Chem.1999,7,9-22.
16.Abrous,L.;Hynes,J.,Jr;Friedrich,S.R.;Smith,A.B.,Ⅲ;Hirschmann,R.Design and Synthesis of Novel Scaffolds for Drug Discovery:Hybrids of-D-Glucose with 1,2,3,4-Tetrahydrobenzo[e][1,4]diazepin-5-one,the Corresponding 1-Oxazepine,and 1-and 4-Pyridyldiazepines.Org.Lett.2001,3,1089-1092.
17.Kennedy,M.L.;Corte's-Selva,F.;Pe'rez-Victoria,J.M.;Jime'nez,I.A.;Gonza' lez,A.G.;Mun~oz,O.M.;Gamarro,F.;Castanys,S.;Ravelo,A.G.Chemosensitization of a Multidrug-Resistant Leishmania tropica Line by New Sesquiterpenes from Maytenus magellanica and Maytenus chubutensis.J.Med.Chem.2001,44,4668-4676.
18.Hirschmann,R.;Ducry,L.;Smith,A.B.,Ⅲ Development of an Efficient,Regio-and Stereoselective Route to Libraries Based on the -D-Glucose Scaffold.J.Org Chem.2000,65,8307-8316.
19.Barakat,K.J.;Cheng,K.;Chan,W.W.-S.;Butler,B.S.;Jacks,T.M.;Schleim,K.D.;Hora,D.F.;Hickey,G.J.;Smith,R.G.;Patchett,A.A.;Nargund,R.P.Synthesis and biological activities of phenyl piperazine- based peptidomimetic growth hormone secretagogues.Bioorg.Med.Chem.Lett.1998,8,1431-1436.
20.Horton,D.A.;Bourne,G.T.;Smythe,M.L.The Combinatorial Synthesis of Bicyclic Privileged Structures or Privileged Substructures.Chem.Rev.2003,103,893-93.
21.Thompson,L.A.;Ellman,J.A.Synthesis and Applications of Small Molecule Libraries.Chem.Rev.1996,96,555-600.
22.Mason,J.S.;Morize,1.;Menard,P.R.;Cheney,D.L.;Hulme,C.;Labaudiniere,R.F.New 4-Point Pharmacophore Method for Molecular Similarity and Diversity Applications:Overview of the Method and Applications,Including a Novel Approach to the Design of Combinatorial Libraries Containing Privileged Substructures.J.Med Chem.1999,42,3251-3264.
23.Horton,D.A.;Severinsen,R.;Kofod-Hansen,M.;Bourne,G.T.;Smythe,M.L.A Versatile Synthetic Approach to Peptidyl Privileged Structures Using a "Safety-Catch"Linker.J.Comb.Chem.2005,7,421-435.
24.Nieto,M.J.;Philip,A.E.;Poupaert,J.H.;McCurdy,C.R.Solution-Phase Parallel Synthesis of Spirohydantoins.J.Comb.Chem.2005,7,258-263.
25.Evdokimov,N.M.;Magedov,I.V.;Kireev,A.S.;Kornienko,A.One-Step,Three-Component Synthesis of Pyridines and 1,4-Dihydropyridines with Manifold Medicinal Utility.Org.Lett.2006,8,899-902.
26.Sharma,S.;Saha,B.;Sawant,D.;Kundu,B.Synthesis of Novel N-Rich Polycyclic Skeletons Based on Azoles and Pyridines.J.Comb.Chem.2007,9,783-792.
27.Gregg,B.T.;Tymoshenko,D.O.;Razzano,D.A.;Johnson;M.R.Pyrazolo[1,5-a]pyrimidines.Identification of the Privileged Structure and Combinatorial Synthesis of 3-(Hetero)arylpyrazolo[1,5-a]pyrimidine-6-carboxamides.J.Comb.Chem.2007,9,507-512.
28.Kercher,T.;Rao,C.;Bencsik,J.R.;Josey,J.A.Diversification of the Three-Component Coupling of 1-Aminoheterocycles,Aldehydes,and Isonitriles:Efficient Parallel Synthesis of a Diverse and Druglike Library of Imidazo-and Tetrahydroimidazo[1,1-a]Heterocycles.J.Comb.Chem.2007,9,1177-1187.
29.(a)Wang,S.;Folkes,A.;Chuckowree,I.;Cockcroft,X.;Sohal,S.;Miller,W.;Milton,J.;Wren,S.P.;Vicker,N.;Depledge,P.;Scott,J.;Smith,L.;Jones,H.;Mistry,P.;Faint,R.;Thompson,D.;Cocks,S.Studies on Pyrrolopyrimidines as Selective Inhibitors of Multidrug-Resistance- Associated Protein in Multidrug Resistance.J.Med.Chem.2004,47,1329-1338.
(b)Perner,R.J.;Gu,Y.-G.;Lee,C.-H.;Bayburt,E.K.;McKie,J.;Alexander,K.M.;Kohlhaas,K.L.;Wismer,C.T.;Mikusa,J.;Jarvis,M.F.;Kowaluk,E.A.;Bhagwat,S.S.5,6,7-Trisubstituted 4-Aminopyrido[2,3-d]pyrimidines as Novel Inhibitors of Adenosine Kinase.J.Med.Chem.2003,46,5249-5257.
(c)McGuigan,C.;Pathirana,R.N.;Snoeck,R.;Andrei,G.;De Clercq,E.;Balzarini,J.Discovery of a New Family of Inhibitors of Human Cytomegalovirus(HCMV)Based upon Lipophilic Alkyl Furano Pyrimidine Dideoxy Nucleosides:Action via a Novel Non-Nucleosidic Mechanism.J.Med.Chem.2004,47,1847-1851.
(d)Gangjee,A.;Zeng,Y.;McGuire,J.J.;Mehraein,F.;Kisliuk,R.L.Synthesis of Classical,Three-Carbon-Bridged 5-Substituted Furo[2,3-d]pyrimidine and 6-Substituted Pyrrolo[2,3-d]pyrimidine Analogues as Antifolates.J.Med.Chem.2004,47,6893-6901.
(e)Rewcastle,G.W.; Bridges,A.J.;Fry,D.W.;Rubin,J.R.;Denny,W.A.Tyrosine Kinase Inhibitors.12.Synthesis and Structure-Activity Relationships for 6-Substituted 4-(Phenylamino)pyrimido[5,4-d]pyrimidines Designed as Inhibitors of the Epidermal Growth Factor Receptor.J.Med.Chem.1997,40,1820-1826.
(f)Griffin,R.J.;Fontana,G.;Golding,B.T.;Guiard,S.;Hardcastle,I.R.;Leahy,J.J.J.;Martin,N.;Richardson,C.;Rigoreau,L.;Stockley,M.;Smith,G.C.M.Selective Benzopyranone and Pyrimido[2,1-a]isoquinolin-4-one Inhibitors of DNA-Dependent Protein Kinase:Synthesis,Structure-Activity Studies,and Radiosensitization of a Human Tumor Cell Line in Vitro.J.Med.Chem.2005,48,569-585.
30.Kompis,I.M.;Islam,K.;Then,R.L.DNAand RNA Synthesis:Antifolates.Chem,Rev.,2005,105,593-620.
31.Gangjee,A.;Shi,J.;Queener,S.F.Synthesis and Biological Activities of Conformationally Restricted,Tricyclic Nonclassical Antifolates as Inhibitors of Dihydrofolate Reductases.J.Med.Chem.1997,40,1930-1936.
32.McGuire,J.J.Anticancer Antifolates:Current Status and Future Directions.Curr.Pharm.Des.2003,9,2593-2613.
33.Ridley,R.G.Nature,2002,415,686.
34.(a)Gangjee,A.;Shi,J.;Queener,S.F.Synthesis of N- {4-[(2,4-Diamino-5-methyl-4,7-dihydro-3Hpyrrolo[2,3-d]pyrimidin-6-yI)thio]benzoy l}-L-glutamic Acid and N -{4-[(1-Am ino-4-oxo-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]ben zoyl}-L-glutamic Acid as Dual Inhibitors of Dihydrofolate Reductase and Thymidylate Synthase and as Potential Antitumor Agents.J.Med.Chem.2005,48,7215-7222.
(b)Gangjee,A.;Zeng,Y.;Talreja,T.;McGuire,J.J.;Kisliuk,R.L.;Queener,S.F.Design and Synthesis of Classical and Nonclassical 6-Arylthio-2,4-diamino-5-ethylpyrrolo[2,3-d]pyrimidines as Antifolates.J.Med.Chem.2007,50,3046-3053.
(c)Gangjee,A.;Li,W.;Yang,J,;Kisliuk,R.L.Design,Synthesis,and Biological Evaluation of Classical and Nonclassical 1-Amino-4-oxo-5-substituted-6-methylpyrrolo[3,1-d]pyrimidines as Dual Thymidylate Synthase and Dihydrofolate Reductase Inhibitors.J.Med.Chem.2008,51,68-76.
(d)Gangjee,A.;Jain,H.D.;Phan,J.;Lin,X.;Song,X.;McGuire,J.J.;Kisliuk,R.L.Dual Inhibitors of Thymidylate Synthase and Dihydrofolate Reductase as Antitumor Agents:Design,Synthesis,and Biological Evaluation of Classical and Nonclassical Pyrrolo[2,3-d]pyrimidine Antifolates.J.Med.Chem.2006,49,1055-1065.
35.Fredholm,B.B.;Ijzerman,A.P.;Jacobson,K.A.;Klotz,K.N.;Linden,J.Pharmacol.Rev.2001,53,527.
36.(a)Muller,C.E.Curr.Top.Med.Chem.2003,3,445.
(b)Fishman,P.;Madi,L.;Bar-Yehuda,S.;Barer,F.;Del Valle,L.;Khalili,K.Oncogene.2002,21,4060.
(c)Merighi,S.;Prisco,M.;Varani,K.;Gessi,S.;Leung,E.;Baraldi,P.G.;Tabrizi,M.A.;Borea,P.A.Pharmacol.Ther.2003,100,31.
(d)Okamura,T.;Kurogi,Y.;Hashimota,K.;Sato,S.;Nishikawa,H.;Kiryu,K.;Nagao,Y.Bioorg.Med.Chem.Lett.2004,14,3775.
37.(a)Muller,C.E.;Thorand,M.;Qurishi,R.;Diekmann,M.;Jacobson,K.A.;Padgett,W.L.;Daly,J.W.Imidazo[2,1-i]purin-5-ones and Related Tricyclic Water-Soluble Purine Derivatives:Potent A2A- and A3-Adenosine Receptor Antagonists.J.Med.Chem.2002,45,3440-3450.
(b)Francis,J.E.;Cash,W.D.;Psychoyos,S.;Ghai,G.;Wenk,P.;Friedmann,R.C.;Atkins,C.;Warren,V.;Furness,P.;Hyun,J.L.;Stone,G.A.;Desai,M.;Williams,M.Structure-Activity Profile of a Series of Novel Triazoloquinazoline Adenosine Antagonists.J.Med.Chem.1988,31,1014-1020.
(c)Baraldi,P.G.;Cacciari,B.;Romagnoli,R.;Merighi,S.;Varani,K.;Borea,P.A.;Spalluto,G.A3 Adenosine Receptor Ligands:History and Perspectives.Med.Res.ReV.2000,20,103-128.
38.Barbara Cosimelli,Giovanni Greco,Marina Ehlardo,Ettore Novellino,Federico Da Settimo,§ Sabrina Taliani,§Concettina La Motta,§ Marusca Bellandi,§ Tiziano Tuccinardi,§ Adriano Martinelli,Osele Ciampi,Derivatives of 4-Amino-6-hydroxy-1-mercaptopyrimidine as Novel,Potent,and Selective A3Adenosine Receptor Antagonists.J.Med.Chem.2008,51,1764-1770.
39.Kalla,R.V.;Elzein,E.;Perry,T.;Li,X.;Palle,V.;Varkhedkar,V.;Gimbel,A.;Maa,T.;Zeng,D.;Zablocki,J.Novel 1,3-Disubstituted 8-(1-benzyl-1H-pyrazol-4-yl)Xanthines:High Affinity and Selective A2B Adenosine Receptor Antagonists.J.Med.Chem.2006,49,3682-3692.
40.Chang,L.C.W.;Spanjersberg,R.F.;von Frijtag Drabbe Kunzel,J.K.;Mulder-Krieger,T.;Brussee,J.;IJzerman,A.P.2,6-Disubstituted and 2,6,8-Trisubstituted Purines as Adenosine Receptor Antagonists.J.Med.Chem.2006,49,2861-2867.
41.(a)Slee,D.H.;Zhang,X.;Moorjani,M.;Lin,E.;Lanier,M.C.;Chen,Y.;Rueter,J.K.;Lechner,S.M.;Markison,S.;Malany,S.;Joswig,T.;Santos,M.;Gross,R.S.;Williams,J.P.;Castro-Palomino,J.C.;Crespo,M.I.;Prat,M.;Gual,S.;Diaz,J.;Wen,J.;O'Brien,Z.;Saunders,J.Identification of Novel,Water-Soluble,1-Amino-N-pyrimidin-4-yl Acetamides as A2A Receptor Antagonists with In Vivo Efficacy.J.Med.Chem.2008,51,400-406.
(b)Slee,D.H.;Chen,Y.;Zhang,X.;Moorjani,M.;Lanier,M.C.;Lin,E.; Rueter,J.K.;Williams,J.P.;Lechner,S.M.;Markison,S.;Malany,S.;Santos,M.;Gross,R.S.;Jalali,K.;Sai,Y.;Zuo,Z.;Yang,C.;Castro-Palomino,J.C.;Crespo,M.I.;Prat,M.;Gual,S.;Diaz,J.-L.;Saunders,J.1-Amino-N-pyrimidin-4-ylacetamides as A2A Receptor Antagonists:1.Structure-Activity Relationships and Optimization of Heterocyclic Substituents.J.Med.Chem.2008,51,1719-1729.
42.Morizzo,E.;Capelli,F.;Lenzi,O.;Catarzi,D.;Varano,F.;Filacchioni,G.;Vincenzi,F.;Varani,K.;Andrea Borea,P.;Colotta,V.;Moro,S.Scouting Human A3 Adenosine Receptor Antagonist Binding Mode Using a Molecular Simplification Approach:From Triazoloquinoxaline to a Pyrimidine Skeleton as a Key Study.J.Med.Chem.2007,50,6596-5606.
43.(a)Patrick,D.R.;Heimbrook,D.C.Protein kinase inhibitors for the treatment of cancer.Drug Discovery Today 1996,1,325-330.
(b)Gill,A.Protein kinases in drug discovery and development.Drug Discovery Today 2004,9,16-17.
(c)Shawver,L.K.;Lipson,K.E.;Fong,T.A.T.;McMahon,G.;Plowman,G.D.;Strawn,L.M.Receptor tyrosine kinases as targets for inhibition of angiogenesis.Drug Discovery Today 1997,2,50-63.
44.Bridges,A.J.Chemical Inhibitors of Protein Kinases.Chem.Rev.2001,101,2541-2572.4
5.Showalter,H.D.H.;Bridges,A.J.;Zhou,H.;Sercel,A.D.;McMichael,A.;Fry,D.W.Tyrosine Kinase Inhibitors.16.6,5,6-Tricyclic Benzothieno[3,1-d]pyrimidines and Pyrimido[5,4-b]- and -[4,5-b]indoles as Potent Inhibitors of the Epidermal Growth Factor Receptor Tyrosine Kinase.J.Med.Chem.1999,42,5464-5474.
46.(a)Smith,L.Ⅱ;Piatnitski,E.L.;Kiselyov,A.S.;Ouyang,X.H.;Chen X.L.;Burdzovic-Wizemann,S.;Xu,Y.J.;Wang,Y.;Rosler,R.L.;Patel,S.N.;Chiang,H.-H.;Milligan,D.L.;Columbus,J.;Wong,W.C.;Doody,J.F.and Hadari,Y.R.Tricyclic azepine derivatives:Pyrimido[4,5-b]-1,4-benzoxazepines as a novel class of epidermal growth factor receptor kinase inhibitors.Bioorg.Med.Chem.Lett.2006,16,1643-1646.
(b)Smith Ⅱ,L.;Wong,W.C.;Kiselyov,A.S.;Burdzovic-Wizemann,S.;Mao,Y.;Xu,Y.;Duncton,M.A.J.;Kim,K.;Piatnitski,E.L.;Doody,J.F.;Wang,Y.;Rosler,R.L.;Milligan,D.;Columbus,J.;Balagtas,C.;Lee,S.P.;Konovalov,A.;Hadari,Y.R.Novel tricyclic azepine derivatives:Biological evaluation of pyrimido[4,5-b]-1,4-benzoxazepines,thiazepines,and diazepines as inhibitors of the epidermal growth factor receptor tyrosine kinase.Bioorg.Med.Chem.Lett.2006,16,5102-5106.
47.Rewcastle,G.W.;Bridges,A.J.;Fry,D.W.;Rubin,J.R.;Denny,W.A.Tyrosine Kinase Inhibitors.12.Synthesis and Structure-Activity Relationships for 6-Substituted 4-(Phenylamino)pyrimido[5,4-d]pyrimidines Designed as Inhibitors of the Epidermal Growth Factor Receptor.J.Med.Chem.1997,40,1820-1826.
48.Manetti,F.;Brullo,C.;Magnani,M.;Mosci,F.;Chelli,B.;Crespan,E.;Schenone,S.;Naldini,A.;Bruno,O.;Trincavelli,M.L.;Maga,G.;Carraro,F.;Martini,C.;Bondavalli,F.;Botta,M.Structure-Based Optimization of Pyrazolo[3,4-d]pyrimidines as Abl Inhibitors and Antiproliferative Agents toward Human Leukemia Cell Lines.J.Med.Chem.2008,51,1252-1259.
49.Echalier,A.;Bettayeb,K.;Ferandin,Y.;Lozach,O.;Clement,M.;Valette,A.;Liger,F.;Marquet,B.;Morris,J.C.;Endicott,J.A.;Joseph,B.;Meijer,L.Meriolins (3-(Pyrimidin-4-yl)-7-azaindoles):Synthesis,Kinase Inhibitory Activity,Cellular Effects,and Structure of a CDK2/Cyclin A/Meriolin Complex?? J.Med.Chem.2008,51,737-751.
50.(a)VanderWel,S.N.;Harvey,P.J.;McNamara,D.J.;RePine,J.T.;Keller,P.R.;Quin,J.,Ⅲ;Booth,R.J.;Elliott,W.L.;Dobrusin,E.M.;Fry,D.W.;Toogood,P.L.Pyrido[2,3-d]pyrimidin-7-ones as Specific Inhibitors of Cyclin-Dependent Kinase.J.Med.Chem.2005,48,2371-2387.
(b)Toogood,P.L.;Harvey,P.J.;Repine,J.T.;Sheehan,D.J.:VanderWel,S.N.;Zhou,H.;Keller,P.R.;McNamara,D.J.;Sherry,D.;Zhu,T.;Brodfuehrer,J.;Choi,C.;Barvian,M.R.;Fry,D.W.Discovery of a Potent and Selective Inhibitor of Cyclin-Dependent Kinase.J.Med.Chem.2005,48,2388-2406.
51.Gaillard,P.;Jeanclaude-Etter,I.;Ardissone,V.;Arkinstall,S.;Cambet,Y.;Camps,M.;Chabert,C.;Church,D.;Cirillo,R.;Gretener,D.;Halazy,S.;Nichols,A.;Szyndralewiez,C.;Vitte,P.-A.;Gotteland,J.-P.Design and Synthesis of the First Generation of Novel Potent,Selective,and in Vivo Active (Benzothiazol-1-yl)acetonitrile Inhibitors of the c-Jun N-Terminal Kinase.J.Med.Chem.2005,48,4596-4607.
52.Klutchko,S.R.;Zhou,H.;Winters,R.T.;Tran,T.P.;Bridges,A.J.;Althaus,I.W.;Amato,D.M.;Elliott,W.L.;Ellis,P.A.;Meade,M.A.;Roberts,B.J.;Fry,D.W.;Gonzales,A.J.;Harvey,P.J.;Nelson,J.M.;Sherwood,V.;Han,H.-K.;Pace,G.;Smaill,J.B.;Denny,W.A.;Showalter,H.D.H.Tyrosine Kinase Inhibitors.19.6-Alkynamides of 4-Anilinoquinazolines and 4-Anilinopyrido[3,4-d]pyrimidines as Irreversible Inhibitors of the erbB Family of Tyrosine Kinase Receptors.J.Med.Chem.2006,49,1475-1485.
53.Sabat,M.;VanRens,J.C.;Brugel,T.A.;Maier,J.;Laufersweiler,M.J.;Golebiowski,A.;De,B.;Easwaran,V.;Hsieh,L.C.;Rosegen,J.;Berberich,S.;Suchanek,E.and Janusz, M.J.The development of novel 1,1-dihydro-pyrimido[4,5-c]pyridazine based inhibitors of lymphocyte specific kinase(Lck).Bioorg.Med.Chem.Lett.2006,16,4257-4261.
54.Bookser,B.C.;Ugarkar,B.G.;Matelich,M.C.;Lemus,R.H.;Allan,M.;Tsuchiya,M.;Nakane,M.;Nagahisa,A.;Wiesner,J.B.;Erion,M.D.Adenosine Kinase Inhibitors.6.Synthesis,Water Solubility,and Antinociceptive Activity of 5-Phenyl-7-(5-deoxy-a-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidines Substituted at C4with Glycinamides and Related Compounds.J.Med.Chem.2005,48,7808-7820.
55.Boyer,S.H.;Ugarkar,B.G.;Solbach,J.;Kopcho,J.;Matelich,M.C.;Ollis,K.;Gomez-Galeno,J.E.;Mendonca,R.;Tsuchiya,M.;Nagahisa,A.;Nakane,M.;Wiesner,J.B.;Erion,M.D.Adenosine Kinase Inhibitors.5.Synthesis,Enzyme Inhibition,and Analgesic Activity of Diaryl-erythro-furanosyltubercidin Analogues.J.Med.Chem.2005,48,6430-6441.
56.Caldwell,J.J.;Davies,T.G.;Donald,A.;McHardy,T.;Rowlands,M.G.;Aherne,G.W.;Hunter,L.K.;Taylor,K.;Ruddle,R.;Raynaud,F.I.;Verdonk,M.;Workman,P.;Garrett,M.D.;Collins,I.Identification of 4-(4-Aminopiperidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidines as Selective Inhibitors of Protein Kinase B through Fragment Elaboration.J.Med.Chem.2008,51,2147-2157.
57.Compton,D.R.;Sheng,S.;Carlson,K.E.;Rebacz,N.A.;Lee,I.Y.;Katzenellenbogen,B.S.;Katzenellenbogen,J.A.Pyrazolo[1,5-a]pyrimidines:Estrogen Receptor Ligands Possessing Estrogen Receptor Antagonist Activity.J.Med.Chem.2004,47,5872-5893.
58.Selleri,S.;Bruni,F.;Costagli,C.;Costanzo,A.;Guerrini,G.;Ciciani,G.;Gratteri,P.;Bonaccini,C.;Aiello,P.M.;Besnard,F.;Renad,S.;Costa,B.;Martini,C.Synthesis and Benzodiazepine Receptor Affinity of Pyrazolo[1,5-a]pyrimidine Derivatives.3.New 6-(3-Thienyl)Series as 1 Selective Ligands.J.Med.Chem.2003,46,310-313.
59.Widdowson,K.L.;Elliott,J.D.;Veber,D.F.;Nie,H.;Rutledge,M.C.;McCleland,B.W.;Xiang,J.-N.;Jurewicz,A.J.;Hertzberg,R.P.;Foley,J.J.;Griswold,D.E.;Martin,L.;Lee,J.M.;White,J.R.;Sarau,H.M.Evaluation of Potent and Selective Small-Molecule Antagonists for the CXCR2 Chemokine Receptor.J.Med.Chem.2004,47,1319-1321.
60.Sznaidman,M.L.;Meade,E.A.;Beauchamp,L.M.;Russell,S.;Tisdale,M.The antiinfluenza activity of pyrroo[2,3-d]pyrimidines.Bioorg.Med.Chem.Lett.1996,6,565-568.
61.Huang,C.Q.;Wilcoxen,K.M.;Grigoriadis,D.E.;McCarthy,J.R.;Chen.C.Design and synthesis of 3-(1-pyridyl)pyrazolo[1,5-a]pyrimidines as potent CRFI receptor antagonists.Bioorg.Med.Chem.Lett.2004,14,3943-3947.
62.Yuan,J.;Gulianello,M.Lombaert,S.D.;Brodbeck,R.;Kieltyka,A.;Hodgetts,K.J.3-Aryl pyrazolo[4,3-d]pyrimidine derivatives:nonpeptide CRF-1 antagonists.Bioorg.Med.Chem.Lett.2002,12,2133-2136.
63.Maeda,Y.;Nakano,M.;Sato,H.;Miyazaki,Y.;Schweiker,S.L.;Smith,J.L.;Truesdale,A.T.4-Acylamino-6-arytfuro[2,3-d]pyrimidines:potent and selective glycogen synthase kinase-3 inhi bitors.Bioorg.Med.Chem.Lett.2004,14,3907-3911.
64.(a)Skiles,J.W.;Suh,J.T.;Williams,B.E.;Menard,P.R.;Barton,J.N.;Love,B.;Jones,H.;Neiss,E.S.;Schwab,A.;Mann,W.S.Angiotensin-converting enzyme inhibitors:new orally active 1,4-thiazepine-2,5-diones,1,4-thiazine-2,5-diones,and 1,4-benzothiazepine-2,5-diones possessing antihypertensive activity.J.Med.Chem.1986,29,784-796.
(b)Crescenza,A.;Botta,M.;Corelli,F.;Santini,A.;Tafi,.A.Cyclic Dipeptides.3.1 Synthesis of Methyl (R)-6-[(tert-B utoxycarbonyl)amino]-4,5,6,7-tetrahydro-1-methyl-5-oxo-1,4-thiazepine-3-carboxylate and Its Hexahydro Analogues:Elaboration of a Novel Dual ACE/NEP Inhibitor.J.Org.Chem.1999,64,3019-3025.
(c)Umemiya,H.;Fukasawa,H.;Ebisawa,M.;Eyrolles,L.;Kawachi,E.;Eisenmann,G.;Gronemeyer,H.;Hashimoto,Y.;Shudo,K.;Kagechika,H.Regulation of Retinoidal Actions by Diazepinylbenzoic Acids.1Retinoid Synergists Which Activate the RXR-RAR Heterodimers.J.Med.Chem.1997,40,4221-4234.
(d)Venkatesan,A.M.;Gu,Y.;Dos Santos,O.;Abe,T.;Agarwal,A.;Yang,Y.;Petersen,P.J.;Weiss,W.J.;Mansour,T.S.;Nukaga,M.;Hujer,A.M.;Bonomo,R.A.;Knox,J.R.Structure-Activity Relationship of 6-Methylidene Penems Bearing Tricyclic Heterocycles as Broad-Spectrum -Lactamase Inhibitors:Crystallographic Structures Show Unexpected Binding of 1,4-Thiazepine Intermediates.J.Med.Chem.2004,47,6556-6568.
65.(a)马玉玲;李为美;李雷;李士玉.硫氮卓酮对冠心病心绞痛患者的治疗作用.济宁医学院学报.2004,27,39-40.
(b)曾祥鸿;李芸芸.硫氮卓酮治疗冠心病严重心衰伴哮喘的长期疗效.黔南民族医专学报 2004,17,9-11.
(c)郭勇;韩建峰;吴良村.硫氮卓酮合并化疗治疗晚期实体肿瘤15例临床观察.实用肿瘤杂志.1995,10,125-125.
(d)张世道;江济尘;朱健;顾统元;张亚斋.口服硫氮卓酮对原发性高血压疗效的观察.安徽医科大学学报,1989,52,1.
66.Ellis,C.D.;Oppong,K.A.;Laufersweiler,M.C.;O'Neil,S.V.;Soper,D.L.;Wang,Y.;Wos,J.A.;Fancher,A.N.;Lu,W.;Suchanek,M.K.;Wang,R.L.;De,B.;Demuth,Jr.,T.P.Synthesis and evaluation of thiazepines as interleukin-1β converting enzyme(ICE)inhibitors.Bioorg.Med.Chem.Lett.2006,16,4728-4732.
67.Zask,A.;Kaplan,J.;Du,X.;MacEwan,G.;Sandanayaka,V.;Eudy,N,;Levin,J.;Jin,G.;Xu,J.;Cummons,T.;Barone,D.;Ayral-Kaloustian,S.;Skotnicki,J.Synthesis and SAR of diazepine and thiazepine TACE and MMP inhibitors.Bioorg.Med.Chem.Lett.2005,15,1641-1645.
68.Almstead,N.G.;Bradley,R.S.;Pikul,S.;De,B.;Natchus,M.G.;Taiwo,Y.O.;Gu,F.;Williams,L.E.;Hynd,B.A.;Janusz,M.J.;Dunaway,C.M.;Mieling,G.E.Design,Synthesis,and Biological Evaluation of Potent Thiazine- and Thiazepine-Based Matrix Metalloproteinase Inhibitors.J.Med.Chem.1999,42,4547-4562.
69.(a)Corelli,F.;Manetti,F.;Tafi,A.;Campiani,G.;Nacci,V.;Botta,M.Diltiazem-like Calcium Entry Blockers:A Hypothesis of the Receptor-Binding Site Based on a Comparative Molecular Field Analysis Model.J.Med.Chem.1997,40,125-131.
(b)Corelli,F.;Dei,D.;Delle Monache,G.;Botta,B.;De Luca,C.;Carmignani,M.;Volpe,A.R.;Botta,M.Synthesis and preliminary pharmacological evaluation of analogues of caracasanamide,a hypotensive natural product.Bioorg.Med.Chem.Lett.1996,6,653-658.
(c)Delle Monache,G.;Botta,B.;Delle Monache,F.;Espinal,R.;De Bonnevaux,S.C.;De Luca,C.;Botta,M.;Corelli,F.;Dei,D.;Gacs-Baitz,E.;Carmignani,M.Caracasandiamide,a truxinic hypotensive agent from Verbesina caracasana.Bioorg.Med.Chem.Lett.1996,6,233-238.
(d)Monache,G.D.;Botta,B.;Delle Monache,F.;Espinal,R.;De Bonnevaux,S.C.;De Luca,C.;Botta,M.;Corelli,F.;Carmignani,M.Novel hypotensive agents from Verbesina caracasana.2.Synthesis and pharmacology of caracasanamide.J.Med.Chem.1993,36,2956-2963.
(e)Delle Monache,G.;Botta,B.;Delle Monache,F.;Espinal,R.;De Bonnevaux,S.C.;De Luca,C.;Botta,M.;Corelli,F.;Carmignani,M.Caracasanamide,a novel hypotensive agent from Verbesina caracasana.Bioorg.Med.Chem.Lett.1992,2,415-418.
70.Drewe,J.;Kasibhatla,S.;Tseng,B.;Shelton,E.;Sperandio,D.;Yee,M.R.;Litvak,J.;Sendzik,M.;Spencer,J.R.;Cai,S.X.Discovery of 5-(4-hydroxy-6-methyl-1 -oxo-2H-pyran-3-yl)-7-phenyl-(E)-2,3,6,7-tetrahydro-1,4-thiaz epines as a new series of apoptosis inducers using a cell- and caspase-based HTS assay.Bioorg.Med.Chem.Lett.2007,17,4987-4990.
71.Boulware,S.L.;Bronstein,J.C.;Nordby,E.C.;Weber,P.C.AntiVir.Res.2001,51,111-125.
72.Cale,A.D.;Gero,T.W.;Walker,K.R.;Lo,Y.S.;Welstead,W.J.;Jaques,L.W.;Johnson,A.F.;Leonard,C.A.;Nolan,J.C.;Johnson,D.N.J.Med.Chem.1989,32,2178-2199.
73.Nakao,T.;Tanaka,H.;Yamato,H.;Akagi,T.;Takehara,S.US 5141930;Chem.Abstr.1992,116,194290b.
74.Schlosser,K.M.;Krasutsky,A.P.;Hamilton,H.W.;Reed,J.E.;Sexton,K.Org.Lett.2004,6,819-821.
75.(a)Fiorini,I.;Nacci,V.;Ciani,S.M.;Garofalo,A.;Campiani,G.;Savini,L.;Novellino,E.;Greco,G.;Bernasconi,P.;Mennini,T.Novel Ligands Specific for Mitochondrial Benzodiazepine Receptors:6-arylpyrrolo[2,1-d][1,5]benzothiazepine Derivatives.Synthesis,Structure-Activity Relationships,and Molecular Modeling Studies.J.Med.Chem.1994,37,1427-1438.
(b)Dalpiaz,A.;Bertolasi,V.;Borea,P.A.;Nacci,V.;Fiorini,I.;Campiani,G.;Mennini,T.;Manzoni,C.;Novellino,E.;Greco,G.A Concerted Study Using Binding Measurements,X-ray Structural Data,and Molecular Modeling on the Stereochemical Features Responsible for the Affinity of 6-Arylpyrrolo[2,1-d][1,5]benzothiazepines toward Mitochondrial Benzodiazepine Receptors.J.Med.Chem.1995,38,4730-4738.
(c)Greco,G.;Novellino,E.;Fiorini,I.;Nacci,V.;Campiani,G.;Ciani,S.M.;Garofalo,A.;Bernasconi,P.;Mennini,T.A Comparative Molecular Field Analysis Model for 6-Arylpyrrolo[2,1-d][1,5]benzothiazepines Binding Selectively to the Mitochondrial Benzodiazepine Receptor.J.Med.Chem.1994,37,4100-4108.
76.Hirozumi Inoue,Mikihiko Konda,Tomiki Hashiyama,Hisao Otsuka,Kaoru Takahashi,Mitsunori Gaino,Tadamasa Date,Keiichi Aoe,Mikio Takeda,Sakae Murata,Hiroshi Narita,Taku Nagao.Synthesis of halogen-substituted 1,5-benzothiazepine derivatives and their vasodilating and hypotensive activities.J.Med.Chem.1991,34,675-687.
77.Campiani,G.;Fiorini,I.;De Filippis,M.P.;Ciani,S.M.;Garofalo,A.;Nacci,V.;Giorgi,G.;Sega,A.;Botta,M.;Chiarini,A.;Budriesi,R.;Bruni,G.;Romeo,M.R.;Manzoni,C.;Mennini,T.Cardiovascular Characterization of Pyrrolo[2,1-d][1,5]benzothiazepine Derivatives Binding Selectively to the Peripheral-Type Benzodiazepine Receptor(PBR):From Dual PBR Affinity and Calcium Antagonist Activity to Novel and Selective Calcium Entry Blockers.J.Med.Chem.1996,39,2921-2938.
78.(a)Amblard,M.;Bedos,P.;Olivier,C.;Daffix,I.;Luccarini,J.-M.;Dodey,P.;Pruneau,D.;Paquet,J.-L.;Marti nez,J.Synthesis and Biological Evaluation of Bradykinin B1/B2and Selcctive B1 Receptor Antagonists.J.Med.Chem.2000,43,2381-2386.
(b)Bedos, P.; Amblard, M.; Subra, G.; Dodey, P.; Luccarini, J.-M.; Paquet, J.-L.; Pruneau, D.; Aumelas, A.; Martinez, J. A Rational Approach to the Design and Synthesis of a New Bradykinin B1 Receptor Antagonist. J. Med. Chem. 2000, 43, 2387-2394.
(c) Amblard, M.; Daffix, I.; Berge, G.; Calmes, M.; Dodey, P.; Pruneau, D.; Paquet, J.-L.; Luccarini, J.-M.; Belichard, P.; Martinez, J. Synthesis and Characterization of Bradykinin B2 Receptor Agonists Containing Constrained Dipeptide Mimics. J. Med. Chem. 1999, 42, 4193-4201.
79. (a) Neamati, N.; Turpin, J. A.; Winslow, H. E.; Christensen, J. L.; Williamson, K.; Orr, A.; Rice, W. G.; Pommier, Y.; Garofalo, A.; Brizzi, A.; Campiani, G. Thiazolothiazepine Inhibitors of HIV-1 Integrase. J. Med. Chem. 1999, 42, 3334-3341.
(b) Maruenda, H.; Johnson F. Design and Synthesis of Novel Inhibitors of HIV-1 Reverse Transcriptase. J. Med. Chem. 1995, 38, 2145-2151.
(c) Aiello, F.; Brizzi, A.; Garofalo, A.; Grande, F.; Ragno, G.; Dayam, R.; Neamati, N. Synthesis of novel thiazolothiazepine based HIV-1 integrase inhibitors. Bioorg. Med. Chem. 2004,12, 4459 - 4466.
80. (a) Campiani, G.; Butini, S.; Fattorusso, C.; Catalanotti, B.; Gemma, S.; Nacci, V.; Morelli, E.; Cagnotto, A.; Mereghetti, I.; Mennini, T.; Carli, M.; Minetti, P.; Di Cesare, M. A.; Mastroianni, D.; Scafetta, N.; Galletti, B.; Stasi, M. A.; Castorina, M.; Pacifici, L.; Vertechy, M.; Serio, S. D.; Ghirardi, O.; Tinti, O.; Carminati, P. Pyrrolo[l,3]benzothiazepine-Based Serotonin and Dopamine Receptor Antagonists. Molecular Modeling, Further Structure-Activity Relationship Studies, and Identification of Novel Atypical Antipsychotic Agents. J. Med. Chem. 2004, 47, 143-157.
(b) Campiani, G.; Nacci, V.; Bechelli, S.; Ciani, S. M.; Garofalo, A.; Fiorini, I.; Wikstrom, H.; de Boer, P.; Liao, Y.; Tepper, P. G.; Cagnotto, A.; Mennini, T. New Antipsychotic Agents with Serotonin and Dopamine Antagonist Properties Based on a Pyrrolo[2,1-b][1,3]benzothiazepine Structure. J. Med. Chem. 1998, 41, 3763-3772.
(c) Campiani, G.; Butini, S.; Gemma, S.; Nacci, V.; Fattorusso, C.; Catalanotti, B.; Giorgi, G.; Cagnotto, A.; Goegan, M.; Mennini, T.; Minetti, P.; Di Cesare, M. A.; Mastroianni, D.; Scafetta, N.; Galletti, B.; Stasi, M. A.; Castorina, M.; Pacifici, L.; Ghirardi, O.; Tinti, O.; Carminati, P. Pyrrolo[l,3]benzothiazepine-Based Atypical Antipsychotic Agents. Synthesis, Structure-Activity Relationship, Molecular Modeling, and Biological Studies. J. Med. Chem. 2002, 45, 344-359.
(d) Warawa, E. J.; Migler, B. M.; Ohnmacht, C. J.; Needles, A. L.; Gatos, G. C.; McLaren, F. M.; Nelson, C. L.; Kirkland, K. M. Behavioral Approach to Nondyskinetic Dopamine Antagonists: Identification of Seroquel. J. Med. Chem. 2001, 44, 371-389. (e) Mouithys-Mickalad, A.; Kauffmann, J.-M.; Petit, C.; Bruhwyler,J.;Liao,Y.;Wikstrom,H.;Damas,J.;Delarge,J.;Deby-Dupont,G.;Geczy,J.;Liegeois,J.-F.Electrooxidation Potential as a Tool in the Early Screening for New Safer Clozapine-like Analogues.J.Med.Chem.2001,44,769-776.
(f)Liao,Y.;Venhuis,B.J.;Rodenhuis,N.;Timmerman,W.;Wikstrom,H.;Meier,E.;Bartoszyk,G.D.;Bottcher,H.;Seyfried,C.A.;Sundell,S.New(Sulfonyloxy)piperazinyldibenzazepines as Potential Atypical Antipsychotics:Chemistry and Pharmacological Evaluation.J.Med.Chem.1999,42(12);2235-2244.
81.(a)Effland,R.C.;Davis,L.J.Heterocycl.Chem.1996,33,2055.
(b)Davis,F.A.;Andemichal,Y.W.Tetrahedron Lett.1998,39,3099.
(b)Jeong,I.Y.;Nagao,Y.Tetrahedron Lett.1998,39,8677.
(c)Dietrich,A.;Volmer,A.;Bashir,M.Anal.Chem.1997,69,4143.
(d)Charisson,P.S.Phamrmacological effects of tetrahydroisoquinoline derivatives.Drugs Furure,1989,14,1179.
82.Chen,Y.-H.;Zhang,Y.-H.;Zhang,H.-J.;Liu,D.-Z.;Gu,M.;Li,J.-Y.;Wu,E;Zhu,X.-Z.;Li,J.;Nan,F.-J.Design,Synthesis,and Biological Evaluation of Isoquinoline-1,3,4-trione Derivatives as Potent Caspase-3 Inhibitors.J.Med.Chem.2006,49,1613-1623.
83.Trotter,B.W.;Nanda,K.K.;Kerr,N.R.;Regan,C.R;Lynch,J.J.;Stump,G.L.;Kiss,L.;Wang,J.;Spencer,R.H.;Kane,S.A.;White,R.B.;Zhang,R.;Anderson,K.D.;Liverton,N.J.;McIntyre,C.J.;Beshore,D.C.;Hartman,G.D.;Dinsmore,C.J.Design and Synthesis of Novel Isoquinoline-3-nitriles as Orally Bioavailable Kv1.5 Antagonists for the Treatment of Atrial Fibrillation.J.Med.Chem.2006,49,6954-6957.
84.Perner,R.J.;DiDomenico,S.;Koenig,J.R.;Gomtsyan,A.;Bayburt,E.K.;Schmidt,R.G.;Drizin,I.;Zheng,G.Z.;Turner,S.C.;Jinkerson,T.;Brown,B.S.;Keddy,R.G.;Lukin,K.;McDonald,H.A.;Honore,P.;Mikusa,J.;Marsh,K.C.;Wetter,J.M.;St.George,K.;Jarvis,M.F.;Faltynek,C.R.;Lee,C.-H.In Vitro Structure-Activity Relationship and In Vivo Characterization of 1-(Aryl)-3-(4-(amino)benzyl)urea Transient Receptor Potential Vanilloid 1 Antagonists.J.Med.Chem.2007,50,3651-3660.
85.(a)van Muijlwijk-Koezen,J.E.;Timmerman,H.;Link,R.;van der Goot,H.;IJzerman,A.P.A Novel Class of Adenosine A3 Receptor Ligands.1.3-(1-Pyridinyl)isoquinoline Derivatives.J.Med.Chem.1998,41,3987-3993.
(b)van Muijlwijk-Koezen,J.E.;Timmerman,H.;Link,R.;van der Goot,H.;IJzerman,A.P A Novel Class of Adenosine A3 Receptor Ligands.2.Structure Affinity Profile of a Series of Isoquinoline and Quinazoline Compounds.J.Med.Chem.1998,41,3994-4000.
86.Van Quaquebeke,E.;Mahieu,T.;Dumont,R;Dewelle,J.;Ribaucour,F.;Simon,G.;Sauvage,S.;Gaussin,J.-F.;Tuti,J.;El Yazidi,M.;Van Vynckt,F.;Mijatovic,T.;Lefranc,F.;Darro,F.;Kiss,R.2,2,1-Trichloro-N-({1-[1-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}carbamoyl)acetamide(UNBS3157),a Novel Nonhematotoxic Naphthalimide Derivative with Potent Antitumor Activity.J.Med.Chem.2007,50,4121-4134.
87.(a)Li,D.;Zhao,B.;Sim,S.;Li,T.;Liu,A.;Liu,L.F.;LaVoie,E.J.8,9-Methylenedioxybenzo[i]phenanthridines:Topoisomerase I-Targeting activity and cytotoxicity.Bioorg.Med.Chem.2003,11,3795-3805.
(b)Li,D.;Zhao,B.;Sim,S.;Li,T.;Liu,A.;Liu,L.F.;LaVoie,E.J.2,3-Dimethoxybenzo[i]phenanthridines:topoisomerase I-targeting anticancer agents.Bioorg.Med.Chem.2003,11,521-528.
(c)Makhey,D.;Li,D.;Zhao,B.;Sim,S.;Li,T.;Liu,A.;Liu,L.F.;LaVoie,E.J,Substituted benzo[i]phenanthridines as mammalian topoisomerase-Targeting agents.Bioorg Med.Chem.2003,11,1809-1820.
88.(a)Strumberg,D.;Pommier,Y.;Paull,K.;Jayaraman,M.;Nagafuji,R;Cushman,M.Synthesis of Cytotoxic Indenoisoquinoline Topoisomerase I Poisons.J.Med.Chem.1999,42,446-457.
(b)Xiao,X.;Antony,S.;Pommier,Y.;Cushman,M.On the Binding of Indeno[l,1-c]isoquinolines in the DNA-Topoisomerase I Cleavage Complex.J.Med.Chem.2005,48,3231-3238.
(c)Morrell,A.;Antony,S.;Kohlhagen,G.;Pommier,Y.;Cushman,M.A Systematic Study of Nitrated Indenoisoquinolines Reveals a Potent Topoisomerase I Inhibitor.J.Med.Chem.2006,49,7740-7753.
(d)Morrell,A.;Placzek,M.;Parmley,S.;Grella,B.;Antony,S.;Pommier,Y.;Cushman,M.Optimization of the Indenone Ring of Indenoisoquinoline Topoisomerase I Inhibitors.J.Med.Chem.2007,50,4388-4404.
89.Griffin,R.J.;Fontana,G.;Golding,B.T.;Guiard,S.;Hardcastle,I.R.;Leahy,J.J.J.;Martin,N.;Richardson,C.;Rigoreau,L.;Stockley,M.;Smith,G.C.M.Selective Benzopyranone and Pyrimido[2,1-a]isoquinolin-4-one Inhibitors of DNA-Dependent Protein Kinase:Synthesis,Structure-Activity Studies,and Radiosensitization of a Human Tumor Cell Line in Vitro.J.Med.Chem.2005,48,569-585.
90.Chao,Q.;Deng,L.;Shih,H.;Leoni,L.M.;Genini,D.;Carson,D.A.;Cottam,H.B.Substituted Isoquinolines and Quinazolines as Potential Antiinflammatory Agents.Synthesis and Biological Evaluation of Inhibitors of Tumor Necrosis Factor.J.Med.Chem.1999,42,3860-3873.
91.Orjales,A.;Mosquera,R.;Toledo,A.;Pumar,M.C.;Garcia,N.;Cortizo,L.;Labeaga,L.;Innerarity,A.Syntheses and Binding Studies of New[(Aryl)(aryloxy)methyl]piperidine Derivatives and Related Compounds as Potential Antidepressant Drugs with High Affinity for Serotonin(5-HT)and Norepinephrine(NE)Transporters.J.Med.Chem.2003,46,5511-5532.
92.Salah M.Sami,Robert T.Dorr,David S.Alberts,William A.Remers.1-Substituted 1,1-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones.A new class of antitumor agent.J.Med.Chem.1993,36,765-770.
93.Reinhard,A.;Schneider,Martin.R.;Angerer,S.V.Indolo[2,1-a]isoquinolines.Syntheses,steroid hormone receptor binding affinities,and cytostatic activity.J.Med.Chem.1990,33,153-160.
94.程轩轩,王冬梅,杨得坡.异喹啉类生物碱的生物活性和构效关系研究进展 中草药,2006,37,1900-1904.
95.Ma,W.G.;Fukushi,Y.;Tahara,S.Fungitoxic alkaloids from Hokkaido Corydalis species.Fitoterapia,1999,70,258-265.
96.刘绪文.孙云廷.罂粟碱的临床及药理作用研究进展.中国药物与临床.2006,6,697-299
97.Cho,W.J.;Park,M.J.;Chung,B.H.;Lee,C.O.Synthesis and biological evaluation of 3-arylisoquinolines as antitumor agents.Bioorg.Med.Chem.Lett.1998,8,41-46.
98.Iwassa,K.;Moriyasu,M.;Tachibana,Y.;Kim,H.S.;Wataya,Y.;Wiegrebe,W.;Bastow,K.F.;Cosentino,L.M.;Kozuka,M.;Lee,K.H.Simple isoquinoline and benzylisoquinoline alkaloids potential antimicrobial,antimalarial,cytotoxic,and anti-HIV agents.Bioorg.Med.Chem.2001,9,2871-2884.
99.Greenlee,W.J.;Woodward,R.B.Total synthesis of marasmic acid.J.Am.Chem.Soc.1976,98,6075-6076.
100.张群英,贺广远,吴晓东.四氢小蘖碱的抗心律失常作用.中国药理学通报,1991,6,459-461.
101.邓哲明.活血化瘀中草药之生物活性评估.J.Chin.Med.2004,15,125-136.
102.Bischler A.,Napierslski B.Ber.,1893,26,1903.
103.(a)Sotomayer,N.;Dominguez,E.;Lete,E.Bischler-Napieralski Cyclization-N/C-Alkylation Sequences for the Construction of Isoquinoline Alkaloids.Synthesis of Protoberberines and Benzo[c]phenanthridines via C-2'-Functionalized 3-Arylisoquinolines.J.Org.Chem.1996,61,4062-4072.
(b)Heaney,H.;Shuhaibar,K.F.;Slawin,A.M.Z.Tetrahedron Lett.1996,37,4275;
(c)Banwell,M.G.;Bissett,B.D.; Busato,S.;Cowden,C.J.;Hockless,D.C.R.;Holman,J.W.;Read,R.W.;Wu,A.W.J.Chem.Soc.,Chem.Commun.1995,255;
(d)Siegfried,M.-A.;Hilpert,H.;Rey,M.;Dreiding,A.S.Helv.Chim.Acta 1980,63,938.
104.(a)Manske R.H.The Chemistry of Isoquinolines.Chem.Rev.,1942,30,145-158.
(b)Bergstrom,F.W.Heterocyclic Nitrogen Compounds.Part ⅡA.Hexacyclic Compounds:Pyridine,Quinoline,and Isoquinoline.Chem.Rev.1944,35,77-277.
(c)W.M.Whaley,Org.Reactions,1951,6,75-150.
(d)Thyagarajan,B.S.The Chemistry of Quinolizines.Chem.Rev.1954,54,1019-1064.
(e)Herz,W.;Tocker,S.Furano(3,2-c)pyridines.J.Am.Chem.Soc.1955,77,3554-3556.
(f)Hey,D.H.;Paluel,A.L.The aporphine series.Part Ⅱ.Application of the Bischler-Napieralski reaction to 2-nitrophenyl-N-phenethylacetamides.J.Chem.Soc.1956,4123-4129.
105.Harwood,H.J.;Johnson,T.B.Isoquinoline Derivatives J.Am.Chem.Soc.1933,55,2555-2559.
106.Whaley,W.M.;Hartung,W.H.J.Synthesis of isoquinoline derivatives.Org Chem.1949,14,650-654.
107.Judeh,Z.M.A.;Ching,C.B.;Bu,J.;McCluskey,A.The first Bischler-Napieralski cyclization in a room temperature ionic liquid.Tetrahedron Lett.2002,43,5089-5091.
108.Chern,M.-S.;Li,W.-R.Solid-phase synthesis of isoquinolinones using Bischler-Napieralski cyclization.Tetrahedron Lett.2004,45,8323-8326.
109.(a)Bischler,A.;Napieralski,B.Chem.Ber.1893,26,1891-1903;
(b)Whaley,W.M.;Govindachari,T.R.The Preparation of 3,4-Dihydroisoquinolines and Related Compounds by the Bischler-Napieralski ReactionAdams,R.,Ed.;Organic Reactions;John Wiley andSons.New York,1951;Vol.Ⅵ,pp 74-150;
(c)Tseng,C.K.;Simone,R.A.;Walke,F.H.J.Org.Chem.1973,38,1746-1747;
(d)Fodor,G.;Nagubandi,S.Tetrahedron 1980,36,1279-1300,and references cited therein
110.Spaggiari A,Davoli P,Blaszczak LC,Prati F Spaggiari A,Davoli P,Blaszczak LC,Prati F Synlett 2005,4,661-663.
111.Chakrabarti,Sriparna;Panda,Kausik;Ila,Hiriyakkanavar;Junjappa,Hiriyakkanavar Synthesis of Functionalized 1,2,3,4-Tetrahydro-β-carboline Derived Enamines through Bischler-Napieralski Type Cyclization of Polarized Ketene N,S-Acetals Synlett.2005,2,309-313.
112.(a)Weiping Zheng,Victor I.Nikulin,Anish A.Konkar,Sandeep S.Vansal,Gamal Shams,Dennis R.Feller,Duane D.Miller 2-Amino-4-benzyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridines:Novel Selective 3-Adrenoceptor Agonists J.Med.Chem.1999,42,2287-2294.(b)Paul J.Reider,and Ichiro Shinkai A Modified Bischler-Napieralski Procedure for the Synthesis of 3-Aryl-3,4-dihydroisoquinolines J.Org.Chem.1991,56,6034-6038
113.Angela L.Marquart,Brent L.Podlogar,Edward W.Huber,David A.Demeter,Norton P.Peet,Herschel J.R.Weintraub,Michael R.Angelastro Synthesis of C hiral Hydroxylated Quinolizidines via Vinylogous Bischler-Napieralski Nitrilium Ion Cyclizations J.Org.Chem.1994,59,2092-2100.
114.Churruca,F.;SanMartin,R.;Carril,M.;Urtiaga,M.K.;Solans,X.;Tellitu,I.;Dominguez,E.Direct,Two-Step Synthetic Pathway to Novel Dibenzo[a,c]phenanthridines.J.Org.Chem.2005,70,3178-3187.
115.(a)Sugasawa,S.;Tachikawa,R.Extension of Bischler-Napieralski reaction—Ⅰ:Synthesis of isoquinoline derivatives:A synthesis of rac.-apomorphine dimethyl ether.Tetrahedron,1958,4,205-212.
(b)Sugasawa,S.;Ushioda,S.Extension of the Bischler-Napieralski reaction—Ⅱ:Synthesis ofpyrroline derivatives.Tetrahedron,1959,5,48-52.
(c)Itoh,N.;Sugasawa,S.Bischler-napieralski reaction—Ⅱ:Synthesis of some ketonic isoquinolines.Tetrahedron,1959,6,16-20.
(d)Fujisawa,T.;Sugasawa,S.Extension of Bischler-Napieralski reaction—Ⅳ:Synthesis of some pyridine derivatives.Tetrahedron,1959,7,185-188.
(e)Itoh,N.;Sugasawa,S.Bischler-napieralski reaction—Ⅱ:Synthesis of some ketonic isoquinolines.Tetrahedron Lett.1959,1,24-25.
(f)Morrison,C.G.;Cetenko,W.;Shavel Jr.,J.The Bischler-Napieralski Cyclization of an Imide.J.Org.Chem.1964,29,2771-2772.
(g)Gal,J.;Weinkam,R.J.;Castagnoli Jr.N.Synthesis of cis- and trans-1-(3,4-dimethoxybenzyl)-3,7-dimethyl-5,8-dimethoxy-1,2,3,4-tetrahydroxyisoquin oline.Mechanism of the Bischler-Napieralski reaction.J.Org.Chem.,1974,39,418-421.
116.Wada,Y.;Kaga,H.;Uchiito,S.;Kumazawa,E.;Tomiki,M.;Onozaki,Y.;Kurono,N.;Tokuda,M.;Ohkuma,T.;Orito,K.On the Synthesis of Protopine Alkaloids J.Org.Chem.,2007,72,7301 -7306.
117.Desmaele,D.;Mekouar,K.;d'Angelo,J.Stereocontrolled Elaboration of Quaternary Carbon Centers through the Asymmetric Michael-Type Alkylation of Chiral Imines/Secondary Enamines:Enantioselective Synthesis of(+)-Vincamine.J.Org.Chem.1997,62,3890-3901.
118.Quirante,J.;Escolano,C.;Merino,A.;Bonjoch,J.First Total Synthesis of (±)-Melinonine-E and(±)-Strychnoxanthine Using a Radical Cyclization Process as the Core Ring-Forming Step.J.Org.Chem.1998,63,968-976.
119.Bergmeier,S.C.;Seth,P.P.Aziridine-Allylsilane-Mediated Total Synthesis of (-)-Yohimbane.J.Org.Chem.1999,64,3237-3243.
120.Banwell,M.G.;Harvey,J.E.;Hockless,D.C.R.;Wu,A.W.Electrocyclic Ring-Opening/-Allyl Cation Cyclization Reaction Sequences Involving gem-Dihalocyclopropanes as Substrates:Application to Syntheses of(±)-,(+)-,and (-)-Lycorane.J.Org.Chem.2000,65,4241-4250.
121.Wang,Y.-C.;Georghiou,P.E.First Enantioselective Total Synthesis of(-)-Tejedine.Org.Lett.2002,4,2675-2678.
122.Gurjar,M.K.;Pramanik,C.;Bhattasali,D.;Ramana,C.V.;Mohapatra,D.K.Total Syntheses of Schulzeines B and C.J.Org.Chem.2007,72,6591- 6594.
123.Brodrick,C.I.;Nicholson,J.S.;Short,W.E Heterocyclic derivatives of 1:2-5:6-dibenzocyclohepta- 1:3:5-triene.Part Ⅱ.5-Aryl-2:3-6:7-dibenzo-1-thia-4-azacyclohepta-2:4:6-trienes and their 1:1-dioxides.J.Chem.Soc.1954,3857-3966.
124.Hunziker,F.;Kunzle,F.;Schindler,O.;Schmutz,J.Dibenzo-azepine,-diazepine,-Oxazepine und -thiazepine.3.Mitteilung tiber siebengliedrige Heterocyclen.Helv.Chim.Acta.1964,47,1163-1172.
125.Jarrett,A.D.;Loudon,J.D.Extrusion of sulphur.Part Ⅱ.A new route to phenanthridine derivatives.J.Chem.Soc.1957,3818-3823.
126.(a)Gait,R.H.B.;Loudon,J.D.;Sloan,A.D.B.Extrusion of sulphur.Part Ⅲ.Polycyclic 1:4-thiazepines.J.Chem.Soc.1958,1588-1592.
(b)Gait,R.H.B.;Loudon,J.D.Extrusion of sulphur.Part Ⅳ.Effect of substituents in 11-phenyldibenzo[b,f]-1:4-thiazepine.J.Chem.Soc.1959,885-889.
127.Le Roux,J-R;Desbene,P-L.;Seguin,M.Rearrangement thermiques et photochimiques d'azides d'alkyles tertiaires synthese de dibenzo(b,f)heteroazepines-1,4 et de 11H-dibenzo(b,e)azepinone-11.Tetrahedron Lett.1976,17,3141-3144.
128.Fujii,T.;Hap,W.;Yoshimura,T.New method for the preparation of dibenzo[b,f][1,4]thiazepines.Heteroatom Chemistry 2004,15,246-250.
129.Abd El Latif FM An improved synthesis of pyrazolo[3,4-b][1,5]benzoxazepine,-benzothiazepine and -benzodiazepine derivatives via a convenient one-pot synthesis.J.Heterocycl.Chem.2000,37,1659-1662.
130.Ahmad R,Zia-ul-Haq M,Hameed S,Akhtar H,Duddeck H An unexpected synthesis of novel oxygen-bridged 1,5-benzothiazepine derivatives and their reductive five-membered-ring opening.Monatshefte Fur Chemie 2000,131,393-400.
131.Sathunuru R,Koh B,Zhang HM,Biehl E One-pot synthesis of trans-7-aryl-6H-6a,7-dihydro[1]benzopyrano[3,4-c][1,5]benzothiazepines Heterocycl.2005,65,2493-2503.
132.(a)Ding,H.;Zhang,Y.;Bian,M.;Yao,W.;Ma,C.Concise Assembly of Highly Substituted Furan-Fused 1,4-Thiazepines and Their Diels-Alder Reactions with Benzynes J.Org.Chem.2005,73,578-584.
(b)Ma,C.;Ding,H.;Zhang,Y.;Bian,M.A Ring-Expansion Methodology Involving Multicomponent Reactions:Highly Efficient Access to Polysubstituted Furan-Fused 1,4-Thiazepine Derivatives.Angrew.Chem.,Int.Ed.2006,45,7793-7797.
133.Safonova,T.S.;Nemeryuk,M.P.;Grineva,N.A.;Kermov,M.A.;Likhovidova,M.M.Reactions of 5-amino-6-mercaptopyrimidines with derivatives of p-chloronitrobenzene.synthesis of a new heterocyclic system-pyrimido[4,5-b]-1,4-benzothiazepine.Chem.Heterocycl.Compd.(Engl.Transl.)2001,37,245-250.
134.(a)Yang,J.;Dang,Q.;Liu,J.;Wei,Z.;Wu,J.;Bai,X.Preparation of a Fully Substituted Purine Library J.Comb.Chem.2005,7,474-482.
(b)Liu,J.;Dang,Q.;Wei,Z.;Shi,F.;Bai,X.An Efficient and Regiospecific Strategy to N7-Substituted Purines and Its Application to a Library of Trisubstituted Purines J.Comb.Chem.2006,8,410-416.
(c)Liu,J.;Dang,Q.;Wei,Z.;Zhang,H.;Bai,X.Parallel Solution-Phase Synthesis of a 2,6,8,9-Tetrasubstituted Purine Library via a Sulfur Intermediate J.Comb.Chem.2005,7,627-636.
135.Yang,J.;Che,X.;Dang,Q.;Wei,Z.;Gao,S.;Bai,X.Synthesis of Tricyclic 4-Chloro-pyrimido[4,5-b][1,4]benzodiazepines Org.Lett.2005,7,1541-1543.
136.(a)Che,X.;Zheng,L.;Dang,Q.;Bai,X.Synthesis of novel tricyclic pyrimidine-fused 5,6-dihydrobenzodiazepines via a Pictet-Spengler-like cyclization Tetrahedron,2006,62,2563-2568.
137.(b)Zheng,L.;Xiang,J.;Dang,Q.;Guo,S.;Bai,X.Novel Heterocyclic Scaffold Consisting of Indole-Fused Pteridines J.Comb.Chem.2005;7;813-815.
(c)Zheng,L.;Xiang,J.;Dang,Q.;Guo,S.;Bai,X.Design and Synthesis of a Tetracyclic Pyrimidine-Fused Benzodiazepine Library J.Comb.Chem.2006,8,381-387.
1.(a)Fodor,G.;Nagubandi,S..Correlation of the von Braun,Ritter,Bischler-Napieralski,Beckmann and Schmidt reactions via nitrilium salt intermediates.Tetrahedron 1980,36,1279-1300.
(b)Falco,E.A.;Elion,G.B.;Burgi,E.;Hitchings,G.H.Studies on Condensed Pyrimidine Systems.X.Some 1,3-Oxazolo(5,4-d)pyrimidines.J.Am.Chem.Soc.1952,74,4897-4902.
2.Vyas,G.N.;Shah,N.M.Quinacetophenone monomethyl ether.Org.Syn,Coll.Vol.4,836-838;Vol.31,90-93.
3.(a)Chen,Y.;Evarts,J.B.,Jr.;Torres,E.;Fuchs,R L.Synthesis of Termini-Differentiated 6-Carbon Stereotetrads:An Aikylative Oxidation Strategy for Preparation of the C21-C26 Segment of Apoptolidin.Org.Lett.2002,4,3571-3574.
(b)Kuhler,T.C.;Fryklund,J.;Bergman,N.;Weilitz,J.;Lee,A.;Larsson,H.Structure-Activity Relationship of Omeprazole and Analogs as Helicobacter pylori Urease Inhibitors.J.Med.Chem.1995,38,4906-4916.
4.(a)Lee,D.;Sello,J.K.;Schreiber,S.L.A Strategy for Macrocyclic Ring Closure and Functionalization Aimed toward Split-Pool Syntheses.J.Am.Chem.Soc.1999,121,10648-10649.
(b)Vedejs,E.;Galante,R.J.;Goekjian,P.G.A Thio-Diels-Alder Route to the Azocine Ring System.Total Synthesis of(±)-Otonecine.J.Am.Chem.Soc.1998,120,3613-3622.
(c)Ma,D.;Tang,G.;Kozikowski,A.P.Synthesis of 7-Substituted Benzolactam-V8s and Their Selectivity for Protein Kinase C Isozymes.Org.Lett.2002,4,2377-2380.
(d)Stark,D.;Witt,M.;Oketch-Rabah,H.A.;Jaroszewski,J.W.A New Class of Spermidine-Derived Alkaloids.Org.Lett.2003,5,2793-2796.
(e)Spring,D.R.;Krishnan,S.;Schreiber,S.L.Towards Diversity-Oriented,Stereoselective Syntheses of Biaryl-or Bis(aryl)metal-Containing Medium Rings.J.Am.Chem.Soc.2000,122,5656-5657.
(f)Spring,D.R.;Krishnan,S.;Blackwell,H.E.;Schreiber,S.L.Diversity-Oriented Synthesis of Biaryl-Containing Medium Rings Using a One Bead/One Stock Solution Platform.J.Am.Chem.Soc.2002,124,1354-1363.
(g)Krishnan,S.;Schreiber,S.L.Syntheses of Stereochemically Diverse Nine-Membered Ring-Containing Biaryls.Org.Lett.2004,6,4021-4024.
(h)Illuminati,G.;Mandolini,L.Ring closure reactions of bifunctional chain molecules.Acc.Chem.Res.1981,14,95-102.
1.Stark,B.P.;Duke,A.J.Extrusion Reactions,Pergamon,Oxford,1967.
2.March,J.Advanced Organic Chemistry,3rd Ed.Wiley,New York,1985,937-941.
3.(a)Engel,P.S.;Mechanism of the thermal and photochemical decomposition of azoalkanes.Chem.Rev.1980,80,99-150.
(b)Engel,P.S.;Nalepa,C.J.Photochemical decomposition and isomerization of aliphatic azo compounds.Pure Appl.Chem.1980,52,2621.
(c)Engel,P.S.;Gerth,D.B.Thermolysis of acyclic azoalkanes:simultaneous or stepwise carbon-nitrogen homolysis? J.Am.Chem.Soc.1983,105,6849.
4.Paine,A.J.;Warkentin,J.A relative extrusibility scale and its application to the thermal fragmentation patterns of 5-membered ring diazenes.Can.J.Chem.1981,59,491-505.
5.Maier,G;Pfriem,S;Schafer,U;Matusch,R.Tetra-tert-butyltetrahedrane.Angew.Chem.Int.Ed.Engl.1978,17,520.
6.Cava,M.P.;Schlessinger,R.H.and Van Meter,J.P.The Photolytic Decomposition of Some Sulfones by an Internally Sensitized Path.J.Am.Chem.Soc.1964,86,3173.
7.Cava,M.P.;Mangold,D.1,2-diphenylphenanthro[1]cyclobutadiene:A highly unstable condensed aromatic cyclobutadiene.Tetrahedron Lett.1964,5,1751.
8.Garcia Ruano,J.L.;Alonso de Diego,S.A.;Martin,M.R.;Torrente,E.;Martin Castro,A.M.Efficient Synthesis of Enantiomerically Pure -Alkyl Cyclopropanecarbonitrile Derivatives from Pyrazolines.Org.Lett.2004,6,4945-4948.
9.Chetcuti,P.A.;Knobler,C.B.;Hawthorne,M.F.Intramolecular conversion of a five-membered iridacycle to a three-membered counterpart by carbon dioxide extrusion.Organomet.1986,5,1913-1914.
10.(a)Guziec,F.S.,Jr.;SanFilippo,L.J.Synthetically useful extrusion reactions of organic sulfur,selenium and tellurium compounds.Tetrahedron 1988,44,6241.
(b)Guziec,F.S.,Jr.;SanFilippo,L.J.;Murphy,C.J.;Moustakis,C.A.;Cullen,E.R.Selones as intermediates in the preparation of extremely sterically hindered molecules.Tetrahedron 1985,41,4843.
11.Man,Y.M.;Mak,T.C.W.;Wong,H.N.C.Arene synthesis by extrusion reaction.Part 14.Synthesis of benzo-fused tetraphenylenes and crystal structure of a 4:1 clathrate inclusion compound of dibenzo[b,h]tetraphenylene with p-xylene.J.Org.Chem.1990, 55,3214-3221.
12.Adam,W.;Baumgarten;M.;Maas,W.A Hydrocarbon Hexaradical with Three Localized 1,3-Cyclopentanediyl Triplet Diradicals Linked by 1,3,5-Trimethylenebenzene as Ferromagnetic Coupler:Synthesis of the Azoalkane Precursor,Photochemical Generation of the Polyradical,and EPR Characterization of Its Septet-Spin Ground State.J.Am.Chem.Soc.2000,122,6735-6738.
13.Yang,F.;Lin,S.Preparation and Reduction of Hexahydro[2.2]paracyclophane.J.Org.Chem.1997,62,2727-2731.
14.(a)Paquette,L.Organic Reactions 1977,26,1-71.
(b)Block,E.Reactions of Organosulfur Compounds,Academic Press,New York.1978,75-84.
(c)Durst,T.In Comprehensive Organic Chemistry.
(d)Barton,D.H.R.,Ollis,W.D.,Eds.;Pergamon:Oxford,1984,187-190.
15.Corey,E.J.;Block,E.Sulfur-bridged carbocycles.Ⅱ.Extrusion of the sulfur bridge.J.Org.Chem.1969,34,1233-1240.
16.Philips,J.C.;Swisher,J.V.;Haidukewych D.and Morales,O.Chem.Commun.1971,11,22.
17.Chou,T.-S.;Chen,H.-C.;Yang,W,-C.;Li,W.-S.;Chao,I.;Lee,S.-J.Type-Two Intramolecular Diels-Alder Reactions of Pyrazolo-o-quinodimethanes.J.Org.Chem.2000,65,5760-5767.
18.Yunoki,S.;Takimiya,K.;Aso,Y.;Otsubo,T.A One-Pot Tandem Pictet-Spengler-Diels-Alder Synthesis of Apoyohimbines from 3-Carbomethoxy-2-(formylmethyl)-3-sulfolene.Tetrahedron Lett.1997,38,3071-3074.
19.(a)Scott,G.P.A Derivative of a New Sulfur Heterocycle.J.Am.Chem.Soc.1953,75,6332.
(b)Dimroth,K.and Lenke,G.Chem.Ber.1956,89,2608.
20.Konstantinova,L.S.;Obruchnikova,N.V.;Rakitin,O.A.;Rees,C.W.;Torroba,T.Synthesis of N-unsubstituted bis[1,2]dithiolo[1,4]thiazines and bis[1,2]dithiolopyrroles.J.Chem.Sco.Perkin Trans.1,2000,3421-3427.
21.Marques,M.M.B.;Santos,M.M.M.;Lobo,A.M.;Prabhakar,S.A novel synthesis of arcyriaflavin-A via an intramolecular sulfur extrusion reaction.Tetrahedron Lett.2000,41,9835-9838.
22.Pfeiffer,W.;Dilk,E.;Robberg,H.;Langer,P.Synthesis and Reactivity of 3,4-Dimethyl-4H-1,3,4-thiadiazines.Synlett.2003,15,2392-2394.
23.Gajurel,C.L.;Vaidya,S.R.Extrusion of SO from 1,4-dithiin sulfoxides in dimethylsulfoxide.Indian J.Chem.,Sect.B 1980,19,911-912.
(b)Gajurel,C.L.;Vaidya,S.R.;Shrestha,K.B.Studies on thermal decomposition of 1,4-dithiin sulfoxides in benzene and benzene-3,5-lutidine solvent systems.Indian J.Chem.,Sect.B 1984,18,361-362.
(c)Chow,Y.;Tam,J.N.S.;Blier,J.E.;Szmant,H.H.Mechanism of sulfur monoxide extrusion.J.Chem.Soc.,Chem.Commun.1970,23,604-1605.
(d)Axel,C.;Pierre,G.;Cristian,S.Effect of substituent nature on sulfur extrusion reactions in preparation of the pyrido[2,3-b][1,4]thiazepine framework.Phosphorus,Sulfur Silicon,Relat.Elem.1997,122,59-70.
(e)Fodor,L.;MacLean,D.B.Sulfur extrusion from 1,4-benzothiazepines.Formation of 3-aryl-4-carbomethoxyisoquinolines.Can.J.Chem.1987,65,18-20.
(f)London,J.D.;Young,L.B.Extrusion of sulphur.Part Ⅵ.Novel ring-contractions giving pyridazines and pyrazoles.J.Chem.Soc.1963,5496-5502.
24.(a)Baduenga,J.;Lopez-Ortiz,J.F.;Gotor,V.Formation of a novel N-N bond through SO extrusion.Regioselective synthesis of 1,2,6-thiadiazine S-oxides and pyrazoles.J.Chem.Soc.Chem.commun.1984,891-894.
(b)Baduenga,J.;Lopez-Ortiz,J.F.;Tomas,M.;Gotor,V.An unambiguous synthesis of pyrazoles by sulphur extrusion from 1,2,6-thiadiazines.J.Chem.Soc.perkin Trans.I 1981,1891-1895.
25.Maria,C.and Maria,D.R.Asymmetric Synthesis of Isoquinoline Alkaloids Chem.Rev.2004,104,3341-3370.
26.Bischler A.,Napierslski B.Ber.1893,26,1903.
27.Pictet,A.;Spengler,T.Ber.Dtsch.Chem.Ges.1911,44,2030
28.Knorr,L.Ber.Dtsch.Chem.Ges.1883,16,2597.
29.(a)Manske,R.H.The Chemistry of Isoquinolines.Chem.Rev.1942,30,145-158.
(b)F.W.Bergstrom Heterocyclic Nitrogen Compounds.Part ⅡA.Hexacyclic Compounds:Pyridine,Quinoline,and Isoquinoline.Chem.Rev.1944,35,77-277.
30.(a)Guang,X.D.;Richard,C.L.Synthesis of 3,4-Disubstituted Isoquinolines via Palladium-Catalyzed Cross-Coupling of o-(1-Alkynyl)benzaldimines and Organic Halides.Org.Lett.2001,3,4035-4038.
(b)Kevin,R.R.;Richard,C.L:Synthesis of Isoquinolines and Pyridines via Palladium-Catalyzed Iminoannulation of Internal Acetylenes.J Org.Chem.1998,63,5306-5307.
(c)Guang,X.D.;Richard,C.L.Synthesis of 3,4-Disubstituted Isoquinolines via Palladium-Catalyzed Cross-Coupling of 2-(1-Alkynyl)benzaldimines and Organic Hali.J.Org.Chem.2003,68,920-928.
(d)Mori,M.;Wakamatsu,H.;Tonogaki,K.;Fujita,R.;Kitamura,T.;Sato,Y.Synthesis of Isoquinoline Derivatives Using ROM-RCM of Cyclobutene-yne.J.Org.Chem.2005,70,1066-1069.
31.(a)Nair,V.;Sreekanth,A.R.;Abhilash,N.;Bhadbhade,M.M.;Gonnade,R.C.A Novel Three-Component Reaction for the Diastereoselective Synthesis of 2H-Pyrimido[2,1-a]isoquinolines via 1,4-Dipolar Cycloaddition Org.Lett.2002,4,3575-3577.
(b)Xiang,Z.;Luo,T.;Lu,K.;Cui,J.;Shi,X.;Fathi,R.;Chen,J.;Yang,Z.Concise Synthesis of Isoquinoline via the Ugi and Heck Reactions.Org.Lett.2004,6,3155-3158.
32.Alonso,R.;Campos,P.J.;Garcia,B.;Rodriguez,M.A.New Light-Induced Iminyl Radical Cyclization Reactions of Acyloximes to Isoquinolines.Org.Lett.2006,8,3521-3523.
33.Ghorai,B.K.;Jiang,D.;Herndon,J.W.Novel Synthesis of Isoquinolines Using Isobenzofuran-Nitrile Diels-Alder Reactions.Org.Lett.2003,5,4261-4263.
34.(a)Garcia,E.;Arrasate,S.;Lete,E.;Sotomayor,N.Diastereoselective Intramolecular r-Amidoalkylation Reactions of L-DOPA Derivatives.Asymmetric Synthesis of Pyrrolo[2,1-a]isoquinolines.J.Org.Chem.2005,70,10368-10374.
(b)Pawlas,J.;Vedso,P.;Jakobsen,P.;Huusfeldt,P.O.;Begtrup,M.Synthesis of 1-Hydroxy-Substituted Pyrazolo[3,4-c]- and Pyrazolo[4,3-c]quinolines and -isoquinolines from 4- and 5-Aryl-Substituted 1-Benzyloxypyrazoles.J.Org.Chem.2000,65,9001-9006.
35.Gug,F.;Blondel,M.;Desban,N.;Bouaziz,S.;Vierfonda,J.-M.;Galonsa,H.An expeditious synthesis of 6-aminophenanthridines.Tetrahedron Lett.2005,46,3725-3727.
36.Su,S.;Porco,John A.Jr.;Synthesis of Pyrrolo-isoquinolines Related to the Lamellarins Using Silver-Catalyzed Cycloisomerization/Dipolar Cycloaddition.J.Am.Chem.Soc.2007,129,7744-7745.
37.Nair,V.;Sreekanth,A.R.;Abhilash,N.;Bhadbhade,M.M.;Gonnade,R.C.A Novel Three-Component Reaction for the Diastereoselective Synthesis of 2H-Pyrimido[2,1-a]isoquinolines via 1,4-Dipolar Cycloaddition.Org.Lett.2002,4,3575-3577.
38.(a)Jarrett,A.D.;Loudon,J.D.Extrusion of sulphur.Part Ⅱ.A new route to phenanthridine derivatives.J.Chem.Soc.1957,3818-3823.
(c)Galt,R.H.B.;Loudon,J.D.;Sloan,A.D.B.Extrusion of sulphur.Part Ⅲ.Polycyclic 1:4-thiazepinesJ.Chem. Soc. 1958, 1588-1593.
(d) Glat, R. H. B.; Loudon, J. D. Extrusion of sulphur. Part IV. Effect of substituents in 11-phenyldibenzo[b,f]-1: 4- thiazepine. J. Chem. Soc. 1959, 885-889.
39. (a) Masquelin, T.; Obrecht, D. A novel access to 2,4-substituted quinolines from acetylenic ketones. Tetrahedron 1997, 53, 641-646;
(b) Cabarrocas, G.; Rafel, S.; Ventura, M.; Villalgordo. J. M. A New Approach Toward the Stereoselective Synthesis of Novel Quinolyl Glycines: Synthesis of the Enantiomerically Pure Quinolyl-β-Amino Alcohol Precursors. Synlett. 2000, J, 595-598;
(c) Cabarrocas, G.; Ventura, M.; Maestro, M.; Mahia, J.; Villalgordo, J. M. Synthesis of novel optically pure quinolyl-β-amino alcohol derivatives from 2-amino thiophenol and chiral a-acetylenic ketones and their IBX-mediated oxidative cleavage to N-Boc quinolyl carboxamides. Tetrahedron: Asymmetry 2001, 12, 1851-1863.
40. (a) Bradsher, C. K.; McDonald, J. W. Aromatic Nuclei by the Sulfur Extrusion Reaction. I. Phenanthridizinium Derivatives. J. Org. Chem. 1962, 27, 4475-4478.
(b) Bradsher, C. K.; McDonald, J. W. Aromatic Nuclei by the Sulfur Extrusion Reaction. II. 1 Phenanthridizinium Salts with a Substituent in Ring A. J. Org. Chem. 1962, 27, 4478-4481.
(c) Bradsher, C. K.; McDonald, J. W. J. Aromatic Nuclei by the Sulfur Extrusion Reaction. III. 1 New Benzophenanthridizinium Systems. Org. Chem. 1962, 27, 4481-4485.
41. (a) Safonova, T. S.; Nemeryuk, M. P.; Grineva, N. A.; Keremov, A. F.; Anisimova, O. S.; Solov'eva, N. P. Properties and conversions of pyrimido[4,5-b]-1,4-benzothiazepines. synthesis of a novel heterocyclic system: pyrimido[5,4-c]isoquinoline. Chem. Heterocycl. Compd. (Engl. Transl.) 2004, 40, 1609-1617.
(b) Nemeryuk, M. P.; Grineva, N. A.; Safonova, T. S. Derivatives of pyrimido[5,4-c]isoquinoline. Patent U.S.S.R. 1983, 725427.
42. (a) Roth, M.; Dubs, P.; Gottschi, E.; Eschenmoser, A. Helv. Chim. Acta. 1971, 54, 710.
(b) Guziec, F. S.; Sanfilippo, L. J. Synthetically useful extrusion reactions of organic sulfur, selenium and tellurium compounds. Tetrahedron 1988, 44, 6241-6285.
(c) Sakurai, O.; Ogiku, T.; Takahashi, M.; Hayashi, M.; Yamanaha, T.; Horikawa, H.; Iwasaki, T. A New Synthesis of 1-Alkylcarbapenems Utilizing Eschenmoser Sulfide Contraction of the Novel Thiazinone Intermediates. J. Org. Chem. 1996, 61, 7889-7894.
(d) Mitchell, R. H. A novel reaction of α-chlorosulfides. A new synthesis of diarylethylenes (stilbenes). Tetrahedron Lett. 1973, 14, 4395-4398.
(f) Lee, H. K.; Kim, J.; Pak, C. S. Reaction of thioamides with zinc enolate: Synthesis of vinylogous carbamates. Tetrahedron Lett. 1999,40,2173-2174.
43. (a) Dolle, R. E. Comprehensive Survey of Combinatorial Library Synthesis: 2000. J. Comb. Chem. 2001, 3, 477-517.
(b) Franzen, R. G. Recent Advances in the Preparation of Heterocycles on Solid Support: A Review of the Literature. J. Comb. Chem. 2002, 2, 195-214.
(c) Houghten, R. A.; Pinilla, C.; Appel, J. R.; Blondelle, S. E.; Dooley, C. T.; Eichler, J.; Nefzi, A.; Ostresh, J. M. Mixture-Based Synthetic Combinatorial Libraries. J. Med. Chem. 1999, 42, 3743-3778.
(d) Nefzi, A.; Ostresh, J. M.; Houghten, R. A. The Current Status of Heterocyclic Combinatorial Libraries. Chem. Rev. 1997, 97, 449-472.
(e) Thompson, L. A.; Ellman, J. A. Synthesis and Applications of Small Molecule Libraries. Chem. Rev. 1996, 96, 555-600.
(f) Gordon, E. M.; Barret, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. Applications of Combinatorial Technologies to Drug Discovery. 2. Combinatorial Organic Synthesis, Library Screening Strategies, and Future Directions.J. Med. Chem. 1994, 37, 1385-1401.
44. (a) Hua, G.; Woollins, J. D. The syntheses of sulfides by deoxygenation of sulfoxides using Woollins' reagent. Tetrahedron Lett. 2007, 48, 3677-3684.
(b) Iranpoor, N.; Firouzabadi, H.; Shaterian, H. R. A New Approach to the Reduction of Sulfoxides to Sulfides with 1,3-Dithiane in the Presence of Electrophilic Bromine as Catalyst. J. Org. Chem. 2002, 67, 2826-2830.
(c) Lucien, E.; Greer, A. Electrophilic Oxidant Produced in the Photodeoxygenation of 1,2-Benzodiphenylene Sulfoxide. J. Org. Chem. 2001, 66, 4576-4584.
(d) Nicolaou, K. C.; Koumbis, A. E.; Snyder, S. A.; Simonsen, K. B. Novel Reactions Initiated by Titanocene Methylidenes: Deoxygenation of Sulfoxides, N-Oxides, and Selenoxides. Angew. Chem. Int. Ed. 2000, 39, 2529-2533.
(e) Kikuchi, S.; Konishi, H.; Hashimoto, Y. The deoxygenation of sulfoxide mediated by the Ph3P/Lewis acid combination and the application to the kinetic resolution of racemic phosphines using optically active sulfoxide. Tetrahedron 2005, 61, 3587-3591.
(f) Gurria, G. M.; Posner, G. H. Photochemical deoxygenation of aryl sulfoxides. J. Org. Chem. 1973, 38, 2419-2420.
(g) Guindon, Y.; Atkinson, J. G.; Morton, H. E. Deoxygenation of sulfoxides with boron bromide reagents. J. Org. Chem. 1984, 49, 4538-4540.
45. (a) Sakamoto, M.; Yamamoto, K; lsshiki, K.; lshikura, T.; Fukagawa, Y.; Yoshioka, T. Antibacterial activity and chemical modifications of ps-5 at the c-3 side chain. J. Antibiotics 1990, 43, 1254-1270 and references cited therein.
(b) Takemura, M.; Higashi, K.; Fujiwara, H.; Sato, M.; Furukawa, M. Chem. Pharm. Bull. 1986, 34, 1089-1093.
(c) Rao, V. S.; Remillard, R.; Menard, M. antibacterial activity and chemical modifications of ps-5 at the c-3 carbapenem antibiotics: displacement of c-3 sulfur side chain by another thiol moiety, and quatemization of a weaker pyridine nitrogen over a stronger primary amine (preparation of BMY 40732 and BMY 40886)side chain. Heteroatom Chemistry 1992, 3, 25-31.
(d) Oda, K.; Yoshida, A. Side chain substitution reaction of 2-arylsulfinyl and 2-arylsulfonyl intermediates for 1β-methylcarbapenems. Tetrahedron Lett. 1997, 38, 5687-5690.
2.郭宗儒.药物分子设计.科学出版.2005.
3.仉文升,李安良.药物化学.北京:高等教育出版社.1999
4.Bohacek,R.S.;McMartin,C.;Guida,W.C.Methods for drug discovery:development of potent,selective,orally effective cholecystokinin antagonists.The art and practice of structure-based drug design:a molecular modeling perspective.Med.Res.Rev.1996,16,3-50.
5.Kolb,H.C.;Finn,M.G.;Sharpless,K.B.Click Chemistry:Diverse Chemical Function from a Few Good Reactions.Angew.Chem.Int.Ed.Engl.2001,40,2004-2021.
6.Evans,B.E.;Rittle,K.E.;Bock,M.G.;DiPardo,R.M.;Freidinger,R.M.;Whitter,W.L.;Lundell,G.F.;Veber,D.F.;Anderson,P.S.;Chang,R.S.L.;Lotti,V.J.;Cerino,D.J.;Chen,T.B.;Kling,P.J.;Kunkel,K.A.;Springer,J.P.;Hirshfield,J.Methods for drug discovery:development of potent,selective,orally effective cholecystokinin antagonists.J.Med.Chem.1988,31,2235-2246.
7.Ariens,E.J.;Beld,A.J.;Rodrigues de Miranda,J.F.;Simonis,A.M.In The Receptors A Comprehensive Treatise;O'Brien,R.D.,Ed.Plenum Press:New York,1979,33.
8.Andrews,P.R.;Lloyd,E.J.Molecular conformation and biological activity of central nervous system active drugs.Med.Res.Rev.1982,2,355-393.
9.Converso,A.;Burow,K.;Marzinzik,A.;Sharpless,K.B.;Finn,M.G.2,6-Dichloro-9-thiabicyclo[3.3.1]nonane:A Privileged,Bivalent Scaffold for the Display of Nucleophilic Components.J.Org.Chem.2001,66,4386-4392.
10.Hajduk,P.J.;Bures,M.;Praestgaard,J.;Fesik,S.W.Privileged Molecules for Protein Binding Identified from NMR-Based Screening.J.Med.Chem.2000,43,3443-3447.
11.Lowe,J.A.,Ⅲ;Hageman,D.L.;Drozda,S.E.;McLean,S.;Bryce,D.K.;Crawford,R.T.;Zorn,S.;Morrone,J.;Bordner,J.5-Phenyl-3-ureidobenzazepin-1-ones as Cholecystokinin-B Receptor Antagonists.J.Med.Chem.1994,3 7,3789-3811.
12.Matter,H.;Baringhaus,K.-H.;Naumann,T.;Klabunde,T.;Pirard,B.Computational Approaches Towards the Rational Design of Drug-like Compound Libraries.Comb.Chem.High Throughput Screen.2001,4,453-475.
13.Nicolaou,K.C.;Pfefferkorn,J.A.;Barluenga,S.;Mitchell,H.J.;Roecker,A.J.;Cao,G.-Q.Natural Product-like Combinatorial Libraries Based on Privileged Structures.3.The "Libraries from Libraries" Principle for Diversity Enhancement of Benzopyran Libraries.J.Am.Chem.Soc.2000,122,9968-9976.
14.Nicolaou,K.C.;Pfefferkorn,J.A.;Mitchell,H.J.;Roecker,A.J.;Barluenga,S.;Cao,G.-Q.;Affleck,R.L.;Lillig,J.E.Natural Product-like Combinatorial Libraries Based on Privileged Structures.2.Construction of a 10000-Membered Benzopyran Library by Directed Split-and-Pool Chemistry Using NanoKans and Optical Encoding.J.Am.Chem.Soc.2000,122,9954-9967.
15.Smith,A.B.,Ⅲ;Favor,D.A.;Sprengeler,P.A.;Guzman,M.C.;Carroll,P.J.;Furst,G.T.;Hirschmann,R.Molecular modeling,synthesis,and structures of N-methylated 3,5-linked pyrrolin-4-ones toward the creation of a privileged nonpeptide scaffold.Bioorg.Med.Chem.1999,7,9-22.
16.Abrous,L.;Hynes,J.,Jr;Friedrich,S.R.;Smith,A.B.,Ⅲ;Hirschmann,R.Design and Synthesis of Novel Scaffolds for Drug Discovery:Hybrids of-D-Glucose with 1,2,3,4-Tetrahydrobenzo[e][1,4]diazepin-5-one,the Corresponding 1-Oxazepine,and 1-and 4-Pyridyldiazepines.Org.Lett.2001,3,1089-1092.
17.Kennedy,M.L.;Corte's-Selva,F.;Pe'rez-Victoria,J.M.;Jime'nez,I.A.;Gonza' lez,A.G.;Mun~oz,O.M.;Gamarro,F.;Castanys,S.;Ravelo,A.G.Chemosensitization of a Multidrug-Resistant Leishmania tropica Line by New Sesquiterpenes from Maytenus magellanica and Maytenus chubutensis.J.Med.Chem.2001,44,4668-4676.
18.Hirschmann,R.;Ducry,L.;Smith,A.B.,Ⅲ Development of an Efficient,Regio-and Stereoselective Route to Libraries Based on the -D-Glucose Scaffold.J.Org Chem.2000,65,8307-8316.
19.Barakat,K.J.;Cheng,K.;Chan,W.W.-S.;Butler,B.S.;Jacks,T.M.;Schleim,K.D.;Hora,D.F.;Hickey,G.J.;Smith,R.G.;Patchett,A.A.;Nargund,R.P.Synthesis and biological activities of phenyl piperazine- based peptidomimetic growth hormone secretagogues.Bioorg.Med.Chem.Lett.1998,8,1431-1436.
20.Horton,D.A.;Bourne,G.T.;Smythe,M.L.The Combinatorial Synthesis of Bicyclic Privileged Structures or Privileged Substructures.Chem.Rev.2003,103,893-93.
21.Thompson,L.A.;Ellman,J.A.Synthesis and Applications of Small Molecule Libraries.Chem.Rev.1996,96,555-600.
22.Mason,J.S.;Morize,1.;Menard,P.R.;Cheney,D.L.;Hulme,C.;Labaudiniere,R.F.New 4-Point Pharmacophore Method for Molecular Similarity and Diversity Applications:Overview of the Method and Applications,Including a Novel Approach to the Design of Combinatorial Libraries Containing Privileged Substructures.J.Med Chem.1999,42,3251-3264.
23.Horton,D.A.;Severinsen,R.;Kofod-Hansen,M.;Bourne,G.T.;Smythe,M.L.A Versatile Synthetic Approach to Peptidyl Privileged Structures Using a "Safety-Catch"Linker.J.Comb.Chem.2005,7,421-435.
24.Nieto,M.J.;Philip,A.E.;Poupaert,J.H.;McCurdy,C.R.Solution-Phase Parallel Synthesis of Spirohydantoins.J.Comb.Chem.2005,7,258-263.
25.Evdokimov,N.M.;Magedov,I.V.;Kireev,A.S.;Kornienko,A.One-Step,Three-Component Synthesis of Pyridines and 1,4-Dihydropyridines with Manifold Medicinal Utility.Org.Lett.2006,8,899-902.
26.Sharma,S.;Saha,B.;Sawant,D.;Kundu,B.Synthesis of Novel N-Rich Polycyclic Skeletons Based on Azoles and Pyridines.J.Comb.Chem.2007,9,783-792.
27.Gregg,B.T.;Tymoshenko,D.O.;Razzano,D.A.;Johnson;M.R.Pyrazolo[1,5-a]pyrimidines.Identification of the Privileged Structure and Combinatorial Synthesis of 3-(Hetero)arylpyrazolo[1,5-a]pyrimidine-6-carboxamides.J.Comb.Chem.2007,9,507-512.
28.Kercher,T.;Rao,C.;Bencsik,J.R.;Josey,J.A.Diversification of the Three-Component Coupling of 1-Aminoheterocycles,Aldehydes,and Isonitriles:Efficient Parallel Synthesis of a Diverse and Druglike Library of Imidazo-and Tetrahydroimidazo[1,1-a]Heterocycles.J.Comb.Chem.2007,9,1177-1187.
29.(a)Wang,S.;Folkes,A.;Chuckowree,I.;Cockcroft,X.;Sohal,S.;Miller,W.;Milton,J.;Wren,S.P.;Vicker,N.;Depledge,P.;Scott,J.;Smith,L.;Jones,H.;Mistry,P.;Faint,R.;Thompson,D.;Cocks,S.Studies on Pyrrolopyrimidines as Selective Inhibitors of Multidrug-Resistance- Associated Protein in Multidrug Resistance.J.Med.Chem.2004,47,1329-1338.
(b)Perner,R.J.;Gu,Y.-G.;Lee,C.-H.;Bayburt,E.K.;McKie,J.;Alexander,K.M.;Kohlhaas,K.L.;Wismer,C.T.;Mikusa,J.;Jarvis,M.F.;Kowaluk,E.A.;Bhagwat,S.S.5,6,7-Trisubstituted 4-Aminopyrido[2,3-d]pyrimidines as Novel Inhibitors of Adenosine Kinase.J.Med.Chem.2003,46,5249-5257.
(c)McGuigan,C.;Pathirana,R.N.;Snoeck,R.;Andrei,G.;De Clercq,E.;Balzarini,J.Discovery of a New Family of Inhibitors of Human Cytomegalovirus(HCMV)Based upon Lipophilic Alkyl Furano Pyrimidine Dideoxy Nucleosides:Action via a Novel Non-Nucleosidic Mechanism.J.Med.Chem.2004,47,1847-1851.
(d)Gangjee,A.;Zeng,Y.;McGuire,J.J.;Mehraein,F.;Kisliuk,R.L.Synthesis of Classical,Three-Carbon-Bridged 5-Substituted Furo[2,3-d]pyrimidine and 6-Substituted Pyrrolo[2,3-d]pyrimidine Analogues as Antifolates.J.Med.Chem.2004,47,6893-6901.
(e)Rewcastle,G.W.; Bridges,A.J.;Fry,D.W.;Rubin,J.R.;Denny,W.A.Tyrosine Kinase Inhibitors.12.Synthesis and Structure-Activity Relationships for 6-Substituted 4-(Phenylamino)pyrimido[5,4-d]pyrimidines Designed as Inhibitors of the Epidermal Growth Factor Receptor.J.Med.Chem.1997,40,1820-1826.
(f)Griffin,R.J.;Fontana,G.;Golding,B.T.;Guiard,S.;Hardcastle,I.R.;Leahy,J.J.J.;Martin,N.;Richardson,C.;Rigoreau,L.;Stockley,M.;Smith,G.C.M.Selective Benzopyranone and Pyrimido[2,1-a]isoquinolin-4-one Inhibitors of DNA-Dependent Protein Kinase:Synthesis,Structure-Activity Studies,and Radiosensitization of a Human Tumor Cell Line in Vitro.J.Med.Chem.2005,48,569-585.
30.Kompis,I.M.;Islam,K.;Then,R.L.DNAand RNA Synthesis:Antifolates.Chem,Rev.,2005,105,593-620.
31.Gangjee,A.;Shi,J.;Queener,S.F.Synthesis and Biological Activities of Conformationally Restricted,Tricyclic Nonclassical Antifolates as Inhibitors of Dihydrofolate Reductases.J.Med.Chem.1997,40,1930-1936.
32.McGuire,J.J.Anticancer Antifolates:Current Status and Future Directions.Curr.Pharm.Des.2003,9,2593-2613.
33.Ridley,R.G.Nature,2002,415,686.
34.(a)Gangjee,A.;Shi,J.;Queener,S.F.Synthesis of N- {4-[(2,4-Diamino-5-methyl-4,7-dihydro-3Hpyrrolo[2,3-d]pyrimidin-6-yI)thio]benzoy l}-L-glutamic Acid and N -{4-[(1-Am ino-4-oxo-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]ben zoyl}-L-glutamic Acid as Dual Inhibitors of Dihydrofolate Reductase and Thymidylate Synthase and as Potential Antitumor Agents.J.Med.Chem.2005,48,7215-7222.
(b)Gangjee,A.;Zeng,Y.;Talreja,T.;McGuire,J.J.;Kisliuk,R.L.;Queener,S.F.Design and Synthesis of Classical and Nonclassical 6-Arylthio-2,4-diamino-5-ethylpyrrolo[2,3-d]pyrimidines as Antifolates.J.Med.Chem.2007,50,3046-3053.
(c)Gangjee,A.;Li,W.;Yang,J,;Kisliuk,R.L.Design,Synthesis,and Biological Evaluation of Classical and Nonclassical 1-Amino-4-oxo-5-substituted-6-methylpyrrolo[3,1-d]pyrimidines as Dual Thymidylate Synthase and Dihydrofolate Reductase Inhibitors.J.Med.Chem.2008,51,68-76.
(d)Gangjee,A.;Jain,H.D.;Phan,J.;Lin,X.;Song,X.;McGuire,J.J.;Kisliuk,R.L.Dual Inhibitors of Thymidylate Synthase and Dihydrofolate Reductase as Antitumor Agents:Design,Synthesis,and Biological Evaluation of Classical and Nonclassical Pyrrolo[2,3-d]pyrimidine Antifolates.J.Med.Chem.2006,49,1055-1065.
35.Fredholm,B.B.;Ijzerman,A.P.;Jacobson,K.A.;Klotz,K.N.;Linden,J.Pharmacol.Rev.2001,53,527.
36.(a)Muller,C.E.Curr.Top.Med.Chem.2003,3,445.
(b)Fishman,P.;Madi,L.;Bar-Yehuda,S.;Barer,F.;Del Valle,L.;Khalili,K.Oncogene.2002,21,4060.
(c)Merighi,S.;Prisco,M.;Varani,K.;Gessi,S.;Leung,E.;Baraldi,P.G.;Tabrizi,M.A.;Borea,P.A.Pharmacol.Ther.2003,100,31.
(d)Okamura,T.;Kurogi,Y.;Hashimota,K.;Sato,S.;Nishikawa,H.;Kiryu,K.;Nagao,Y.Bioorg.Med.Chem.Lett.2004,14,3775.
37.(a)Muller,C.E.;Thorand,M.;Qurishi,R.;Diekmann,M.;Jacobson,K.A.;Padgett,W.L.;Daly,J.W.Imidazo[2,1-i]purin-5-ones and Related Tricyclic Water-Soluble Purine Derivatives:Potent A2A- and A3-Adenosine Receptor Antagonists.J.Med.Chem.2002,45,3440-3450.
(b)Francis,J.E.;Cash,W.D.;Psychoyos,S.;Ghai,G.;Wenk,P.;Friedmann,R.C.;Atkins,C.;Warren,V.;Furness,P.;Hyun,J.L.;Stone,G.A.;Desai,M.;Williams,M.Structure-Activity Profile of a Series of Novel Triazoloquinazoline Adenosine Antagonists.J.Med.Chem.1988,31,1014-1020.
(c)Baraldi,P.G.;Cacciari,B.;Romagnoli,R.;Merighi,S.;Varani,K.;Borea,P.A.;Spalluto,G.A3 Adenosine Receptor Ligands:History and Perspectives.Med.Res.ReV.2000,20,103-128.
38.Barbara Cosimelli,Giovanni Greco,Marina Ehlardo,Ettore Novellino,Federico Da Settimo,§ Sabrina Taliani,§Concettina La Motta,§ Marusca Bellandi,§ Tiziano Tuccinardi,§ Adriano Martinelli,Osele Ciampi,Derivatives of 4-Amino-6-hydroxy-1-mercaptopyrimidine as Novel,Potent,and Selective A3Adenosine Receptor Antagonists.J.Med.Chem.2008,51,1764-1770.
39.Kalla,R.V.;Elzein,E.;Perry,T.;Li,X.;Palle,V.;Varkhedkar,V.;Gimbel,A.;Maa,T.;Zeng,D.;Zablocki,J.Novel 1,3-Disubstituted 8-(1-benzyl-1H-pyrazol-4-yl)Xanthines:High Affinity and Selective A2B Adenosine Receptor Antagonists.J.Med.Chem.2006,49,3682-3692.
40.Chang,L.C.W.;Spanjersberg,R.F.;von Frijtag Drabbe Kunzel,J.K.;Mulder-Krieger,T.;Brussee,J.;IJzerman,A.P.2,6-Disubstituted and 2,6,8-Trisubstituted Purines as Adenosine Receptor Antagonists.J.Med.Chem.2006,49,2861-2867.
41.(a)Slee,D.H.;Zhang,X.;Moorjani,M.;Lin,E.;Lanier,M.C.;Chen,Y.;Rueter,J.K.;Lechner,S.M.;Markison,S.;Malany,S.;Joswig,T.;Santos,M.;Gross,R.S.;Williams,J.P.;Castro-Palomino,J.C.;Crespo,M.I.;Prat,M.;Gual,S.;Diaz,J.;Wen,J.;O'Brien,Z.;Saunders,J.Identification of Novel,Water-Soluble,1-Amino-N-pyrimidin-4-yl Acetamides as A2A Receptor Antagonists with In Vivo Efficacy.J.Med.Chem.2008,51,400-406.
(b)Slee,D.H.;Chen,Y.;Zhang,X.;Moorjani,M.;Lanier,M.C.;Lin,E.; Rueter,J.K.;Williams,J.P.;Lechner,S.M.;Markison,S.;Malany,S.;Santos,M.;Gross,R.S.;Jalali,K.;Sai,Y.;Zuo,Z.;Yang,C.;Castro-Palomino,J.C.;Crespo,M.I.;Prat,M.;Gual,S.;Diaz,J.-L.;Saunders,J.1-Amino-N-pyrimidin-4-ylacetamides as A2A Receptor Antagonists:1.Structure-Activity Relationships and Optimization of Heterocyclic Substituents.J.Med.Chem.2008,51,1719-1729.
42.Morizzo,E.;Capelli,F.;Lenzi,O.;Catarzi,D.;Varano,F.;Filacchioni,G.;Vincenzi,F.;Varani,K.;Andrea Borea,P.;Colotta,V.;Moro,S.Scouting Human A3 Adenosine Receptor Antagonist Binding Mode Using a Molecular Simplification Approach:From Triazoloquinoxaline to a Pyrimidine Skeleton as a Key Study.J.Med.Chem.2007,50,6596-5606.
43.(a)Patrick,D.R.;Heimbrook,D.C.Protein kinase inhibitors for the treatment of cancer.Drug Discovery Today 1996,1,325-330.
(b)Gill,A.Protein kinases in drug discovery and development.Drug Discovery Today 2004,9,16-17.
(c)Shawver,L.K.;Lipson,K.E.;Fong,T.A.T.;McMahon,G.;Plowman,G.D.;Strawn,L.M.Receptor tyrosine kinases as targets for inhibition of angiogenesis.Drug Discovery Today 1997,2,50-63.
44.Bridges,A.J.Chemical Inhibitors of Protein Kinases.Chem.Rev.2001,101,2541-2572.4
5.Showalter,H.D.H.;Bridges,A.J.;Zhou,H.;Sercel,A.D.;McMichael,A.;Fry,D.W.Tyrosine Kinase Inhibitors.16.6,5,6-Tricyclic Benzothieno[3,1-d]pyrimidines and Pyrimido[5,4-b]- and -[4,5-b]indoles as Potent Inhibitors of the Epidermal Growth Factor Receptor Tyrosine Kinase.J.Med.Chem.1999,42,5464-5474.
46.(a)Smith,L.Ⅱ;Piatnitski,E.L.;Kiselyov,A.S.;Ouyang,X.H.;Chen X.L.;Burdzovic-Wizemann,S.;Xu,Y.J.;Wang,Y.;Rosler,R.L.;Patel,S.N.;Chiang,H.-H.;Milligan,D.L.;Columbus,J.;Wong,W.C.;Doody,J.F.and Hadari,Y.R.Tricyclic azepine derivatives:Pyrimido[4,5-b]-1,4-benzoxazepines as a novel class of epidermal growth factor receptor kinase inhibitors.Bioorg.Med.Chem.Lett.2006,16,1643-1646.
(b)Smith Ⅱ,L.;Wong,W.C.;Kiselyov,A.S.;Burdzovic-Wizemann,S.;Mao,Y.;Xu,Y.;Duncton,M.A.J.;Kim,K.;Piatnitski,E.L.;Doody,J.F.;Wang,Y.;Rosler,R.L.;Milligan,D.;Columbus,J.;Balagtas,C.;Lee,S.P.;Konovalov,A.;Hadari,Y.R.Novel tricyclic azepine derivatives:Biological evaluation of pyrimido[4,5-b]-1,4-benzoxazepines,thiazepines,and diazepines as inhibitors of the epidermal growth factor receptor tyrosine kinase.Bioorg.Med.Chem.Lett.2006,16,5102-5106.
47.Rewcastle,G.W.;Bridges,A.J.;Fry,D.W.;Rubin,J.R.;Denny,W.A.Tyrosine Kinase Inhibitors.12.Synthesis and Structure-Activity Relationships for 6-Substituted 4-(Phenylamino)pyrimido[5,4-d]pyrimidines Designed as Inhibitors of the Epidermal Growth Factor Receptor.J.Med.Chem.1997,40,1820-1826.
48.Manetti,F.;Brullo,C.;Magnani,M.;Mosci,F.;Chelli,B.;Crespan,E.;Schenone,S.;Naldini,A.;Bruno,O.;Trincavelli,M.L.;Maga,G.;Carraro,F.;Martini,C.;Bondavalli,F.;Botta,M.Structure-Based Optimization of Pyrazolo[3,4-d]pyrimidines as Abl Inhibitors and Antiproliferative Agents toward Human Leukemia Cell Lines.J.Med.Chem.2008,51,1252-1259.
49.Echalier,A.;Bettayeb,K.;Ferandin,Y.;Lozach,O.;Clement,M.;Valette,A.;Liger,F.;Marquet,B.;Morris,J.C.;Endicott,J.A.;Joseph,B.;Meijer,L.Meriolins (3-(Pyrimidin-4-yl)-7-azaindoles):Synthesis,Kinase Inhibitory Activity,Cellular Effects,and Structure of a CDK2/Cyclin A/Meriolin Complex?? J.Med.Chem.2008,51,737-751.
50.(a)VanderWel,S.N.;Harvey,P.J.;McNamara,D.J.;RePine,J.T.;Keller,P.R.;Quin,J.,Ⅲ;Booth,R.J.;Elliott,W.L.;Dobrusin,E.M.;Fry,D.W.;Toogood,P.L.Pyrido[2,3-d]pyrimidin-7-ones as Specific Inhibitors of Cyclin-Dependent Kinase.J.Med.Chem.2005,48,2371-2387.
(b)Toogood,P.L.;Harvey,P.J.;Repine,J.T.;Sheehan,D.J.:VanderWel,S.N.;Zhou,H.;Keller,P.R.;McNamara,D.J.;Sherry,D.;Zhu,T.;Brodfuehrer,J.;Choi,C.;Barvian,M.R.;Fry,D.W.Discovery of a Potent and Selective Inhibitor of Cyclin-Dependent Kinase.J.Med.Chem.2005,48,2388-2406.
51.Gaillard,P.;Jeanclaude-Etter,I.;Ardissone,V.;Arkinstall,S.;Cambet,Y.;Camps,M.;Chabert,C.;Church,D.;Cirillo,R.;Gretener,D.;Halazy,S.;Nichols,A.;Szyndralewiez,C.;Vitte,P.-A.;Gotteland,J.-P.Design and Synthesis of the First Generation of Novel Potent,Selective,and in Vivo Active (Benzothiazol-1-yl)acetonitrile Inhibitors of the c-Jun N-Terminal Kinase.J.Med.Chem.2005,48,4596-4607.
52.Klutchko,S.R.;Zhou,H.;Winters,R.T.;Tran,T.P.;Bridges,A.J.;Althaus,I.W.;Amato,D.M.;Elliott,W.L.;Ellis,P.A.;Meade,M.A.;Roberts,B.J.;Fry,D.W.;Gonzales,A.J.;Harvey,P.J.;Nelson,J.M.;Sherwood,V.;Han,H.-K.;Pace,G.;Smaill,J.B.;Denny,W.A.;Showalter,H.D.H.Tyrosine Kinase Inhibitors.19.6-Alkynamides of 4-Anilinoquinazolines and 4-Anilinopyrido[3,4-d]pyrimidines as Irreversible Inhibitors of the erbB Family of Tyrosine Kinase Receptors.J.Med.Chem.2006,49,1475-1485.
53.Sabat,M.;VanRens,J.C.;Brugel,T.A.;Maier,J.;Laufersweiler,M.J.;Golebiowski,A.;De,B.;Easwaran,V.;Hsieh,L.C.;Rosegen,J.;Berberich,S.;Suchanek,E.and Janusz, M.J.The development of novel 1,1-dihydro-pyrimido[4,5-c]pyridazine based inhibitors of lymphocyte specific kinase(Lck).Bioorg.Med.Chem.Lett.2006,16,4257-4261.
54.Bookser,B.C.;Ugarkar,B.G.;Matelich,M.C.;Lemus,R.H.;Allan,M.;Tsuchiya,M.;Nakane,M.;Nagahisa,A.;Wiesner,J.B.;Erion,M.D.Adenosine Kinase Inhibitors.6.Synthesis,Water Solubility,and Antinociceptive Activity of 5-Phenyl-7-(5-deoxy-a-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidines Substituted at C4with Glycinamides and Related Compounds.J.Med.Chem.2005,48,7808-7820.
55.Boyer,S.H.;Ugarkar,B.G.;Solbach,J.;Kopcho,J.;Matelich,M.C.;Ollis,K.;Gomez-Galeno,J.E.;Mendonca,R.;Tsuchiya,M.;Nagahisa,A.;Nakane,M.;Wiesner,J.B.;Erion,M.D.Adenosine Kinase Inhibitors.5.Synthesis,Enzyme Inhibition,and Analgesic Activity of Diaryl-erythro-furanosyltubercidin Analogues.J.Med.Chem.2005,48,6430-6441.
56.Caldwell,J.J.;Davies,T.G.;Donald,A.;McHardy,T.;Rowlands,M.G.;Aherne,G.W.;Hunter,L.K.;Taylor,K.;Ruddle,R.;Raynaud,F.I.;Verdonk,M.;Workman,P.;Garrett,M.D.;Collins,I.Identification of 4-(4-Aminopiperidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidines as Selective Inhibitors of Protein Kinase B through Fragment Elaboration.J.Med.Chem.2008,51,2147-2157.
57.Compton,D.R.;Sheng,S.;Carlson,K.E.;Rebacz,N.A.;Lee,I.Y.;Katzenellenbogen,B.S.;Katzenellenbogen,J.A.Pyrazolo[1,5-a]pyrimidines:Estrogen Receptor Ligands Possessing Estrogen Receptor Antagonist Activity.J.Med.Chem.2004,47,5872-5893.
58.Selleri,S.;Bruni,F.;Costagli,C.;Costanzo,A.;Guerrini,G.;Ciciani,G.;Gratteri,P.;Bonaccini,C.;Aiello,P.M.;Besnard,F.;Renad,S.;Costa,B.;Martini,C.Synthesis and Benzodiazepine Receptor Affinity of Pyrazolo[1,5-a]pyrimidine Derivatives.3.New 6-(3-Thienyl)Series as 1 Selective Ligands.J.Med.Chem.2003,46,310-313.
59.Widdowson,K.L.;Elliott,J.D.;Veber,D.F.;Nie,H.;Rutledge,M.C.;McCleland,B.W.;Xiang,J.-N.;Jurewicz,A.J.;Hertzberg,R.P.;Foley,J.J.;Griswold,D.E.;Martin,L.;Lee,J.M.;White,J.R.;Sarau,H.M.Evaluation of Potent and Selective Small-Molecule Antagonists for the CXCR2 Chemokine Receptor.J.Med.Chem.2004,47,1319-1321.
60.Sznaidman,M.L.;Meade,E.A.;Beauchamp,L.M.;Russell,S.;Tisdale,M.The antiinfluenza activity of pyrroo[2,3-d]pyrimidines.Bioorg.Med.Chem.Lett.1996,6,565-568.
61.Huang,C.Q.;Wilcoxen,K.M.;Grigoriadis,D.E.;McCarthy,J.R.;Chen.C.Design and synthesis of 3-(1-pyridyl)pyrazolo[1,5-a]pyrimidines as potent CRFI receptor antagonists.Bioorg.Med.Chem.Lett.2004,14,3943-3947.
62.Yuan,J.;Gulianello,M.Lombaert,S.D.;Brodbeck,R.;Kieltyka,A.;Hodgetts,K.J.3-Aryl pyrazolo[4,3-d]pyrimidine derivatives:nonpeptide CRF-1 antagonists.Bioorg.Med.Chem.Lett.2002,12,2133-2136.
63.Maeda,Y.;Nakano,M.;Sato,H.;Miyazaki,Y.;Schweiker,S.L.;Smith,J.L.;Truesdale,A.T.4-Acylamino-6-arytfuro[2,3-d]pyrimidines:potent and selective glycogen synthase kinase-3 inhi bitors.Bioorg.Med.Chem.Lett.2004,14,3907-3911.
64.(a)Skiles,J.W.;Suh,J.T.;Williams,B.E.;Menard,P.R.;Barton,J.N.;Love,B.;Jones,H.;Neiss,E.S.;Schwab,A.;Mann,W.S.Angiotensin-converting enzyme inhibitors:new orally active 1,4-thiazepine-2,5-diones,1,4-thiazine-2,5-diones,and 1,4-benzothiazepine-2,5-diones possessing antihypertensive activity.J.Med.Chem.1986,29,784-796.
(b)Crescenza,A.;Botta,M.;Corelli,F.;Santini,A.;Tafi,.A.Cyclic Dipeptides.3.1 Synthesis of Methyl (R)-6-[(tert-B utoxycarbonyl)amino]-4,5,6,7-tetrahydro-1-methyl-5-oxo-1,4-thiazepine-3-carboxylate and Its Hexahydro Analogues:Elaboration of a Novel Dual ACE/NEP Inhibitor.J.Org.Chem.1999,64,3019-3025.
(c)Umemiya,H.;Fukasawa,H.;Ebisawa,M.;Eyrolles,L.;Kawachi,E.;Eisenmann,G.;Gronemeyer,H.;Hashimoto,Y.;Shudo,K.;Kagechika,H.Regulation of Retinoidal Actions by Diazepinylbenzoic Acids.1Retinoid Synergists Which Activate the RXR-RAR Heterodimers.J.Med.Chem.1997,40,4221-4234.
(d)Venkatesan,A.M.;Gu,Y.;Dos Santos,O.;Abe,T.;Agarwal,A.;Yang,Y.;Petersen,P.J.;Weiss,W.J.;Mansour,T.S.;Nukaga,M.;Hujer,A.M.;Bonomo,R.A.;Knox,J.R.Structure-Activity Relationship of 6-Methylidene Penems Bearing Tricyclic Heterocycles as Broad-Spectrum -Lactamase Inhibitors:Crystallographic Structures Show Unexpected Binding of 1,4-Thiazepine Intermediates.J.Med.Chem.2004,47,6556-6568.
65.(a)马玉玲;李为美;李雷;李士玉.硫氮卓酮对冠心病心绞痛患者的治疗作用.济宁医学院学报.2004,27,39-40.
(b)曾祥鸿;李芸芸.硫氮卓酮治疗冠心病严重心衰伴哮喘的长期疗效.黔南民族医专学报 2004,17,9-11.
(c)郭勇;韩建峰;吴良村.硫氮卓酮合并化疗治疗晚期实体肿瘤15例临床观察.实用肿瘤杂志.1995,10,125-125.
(d)张世道;江济尘;朱健;顾统元;张亚斋.口服硫氮卓酮对原发性高血压疗效的观察.安徽医科大学学报,1989,52,1.
66.Ellis,C.D.;Oppong,K.A.;Laufersweiler,M.C.;O'Neil,S.V.;Soper,D.L.;Wang,Y.;Wos,J.A.;Fancher,A.N.;Lu,W.;Suchanek,M.K.;Wang,R.L.;De,B.;Demuth,Jr.,T.P.Synthesis and evaluation of thiazepines as interleukin-1β converting enzyme(ICE)inhibitors.Bioorg.Med.Chem.Lett.2006,16,4728-4732.
67.Zask,A.;Kaplan,J.;Du,X.;MacEwan,G.;Sandanayaka,V.;Eudy,N,;Levin,J.;Jin,G.;Xu,J.;Cummons,T.;Barone,D.;Ayral-Kaloustian,S.;Skotnicki,J.Synthesis and SAR of diazepine and thiazepine TACE and MMP inhibitors.Bioorg.Med.Chem.Lett.2005,15,1641-1645.
68.Almstead,N.G.;Bradley,R.S.;Pikul,S.;De,B.;Natchus,M.G.;Taiwo,Y.O.;Gu,F.;Williams,L.E.;Hynd,B.A.;Janusz,M.J.;Dunaway,C.M.;Mieling,G.E.Design,Synthesis,and Biological Evaluation of Potent Thiazine- and Thiazepine-Based Matrix Metalloproteinase Inhibitors.J.Med.Chem.1999,42,4547-4562.
69.(a)Corelli,F.;Manetti,F.;Tafi,A.;Campiani,G.;Nacci,V.;Botta,M.Diltiazem-like Calcium Entry Blockers:A Hypothesis of the Receptor-Binding Site Based on a Comparative Molecular Field Analysis Model.J.Med.Chem.1997,40,125-131.
(b)Corelli,F.;Dei,D.;Delle Monache,G.;Botta,B.;De Luca,C.;Carmignani,M.;Volpe,A.R.;Botta,M.Synthesis and preliminary pharmacological evaluation of analogues of caracasanamide,a hypotensive natural product.Bioorg.Med.Chem.Lett.1996,6,653-658.
(c)Delle Monache,G.;Botta,B.;Delle Monache,F.;Espinal,R.;De Bonnevaux,S.C.;De Luca,C.;Botta,M.;Corelli,F.;Dei,D.;Gacs-Baitz,E.;Carmignani,M.Caracasandiamide,a truxinic hypotensive agent from Verbesina caracasana.Bioorg.Med.Chem.Lett.1996,6,233-238.
(d)Monache,G.D.;Botta,B.;Delle Monache,F.;Espinal,R.;De Bonnevaux,S.C.;De Luca,C.;Botta,M.;Corelli,F.;Carmignani,M.Novel hypotensive agents from Verbesina caracasana.2.Synthesis and pharmacology of caracasanamide.J.Med.Chem.1993,36,2956-2963.
(e)Delle Monache,G.;Botta,B.;Delle Monache,F.;Espinal,R.;De Bonnevaux,S.C.;De Luca,C.;Botta,M.;Corelli,F.;Carmignani,M.Caracasanamide,a novel hypotensive agent from Verbesina caracasana.Bioorg.Med.Chem.Lett.1992,2,415-418.
70.Drewe,J.;Kasibhatla,S.;Tseng,B.;Shelton,E.;Sperandio,D.;Yee,M.R.;Litvak,J.;Sendzik,M.;Spencer,J.R.;Cai,S.X.Discovery of 5-(4-hydroxy-6-methyl-1 -oxo-2H-pyran-3-yl)-7-phenyl-(E)-2,3,6,7-tetrahydro-1,4-thiaz epines as a new series of apoptosis inducers using a cell- and caspase-based HTS assay.Bioorg.Med.Chem.Lett.2007,17,4987-4990.
71.Boulware,S.L.;Bronstein,J.C.;Nordby,E.C.;Weber,P.C.AntiVir.Res.2001,51,111-125.
72.Cale,A.D.;Gero,T.W.;Walker,K.R.;Lo,Y.S.;Welstead,W.J.;Jaques,L.W.;Johnson,A.F.;Leonard,C.A.;Nolan,J.C.;Johnson,D.N.J.Med.Chem.1989,32,2178-2199.
73.Nakao,T.;Tanaka,H.;Yamato,H.;Akagi,T.;Takehara,S.US 5141930;Chem.Abstr.1992,116,194290b.
74.Schlosser,K.M.;Krasutsky,A.P.;Hamilton,H.W.;Reed,J.E.;Sexton,K.Org.Lett.2004,6,819-821.
75.(a)Fiorini,I.;Nacci,V.;Ciani,S.M.;Garofalo,A.;Campiani,G.;Savini,L.;Novellino,E.;Greco,G.;Bernasconi,P.;Mennini,T.Novel Ligands Specific for Mitochondrial Benzodiazepine Receptors:6-arylpyrrolo[2,1-d][1,5]benzothiazepine Derivatives.Synthesis,Structure-Activity Relationships,and Molecular Modeling Studies.J.Med.Chem.1994,37,1427-1438.
(b)Dalpiaz,A.;Bertolasi,V.;Borea,P.A.;Nacci,V.;Fiorini,I.;Campiani,G.;Mennini,T.;Manzoni,C.;Novellino,E.;Greco,G.A Concerted Study Using Binding Measurements,X-ray Structural Data,and Molecular Modeling on the Stereochemical Features Responsible for the Affinity of 6-Arylpyrrolo[2,1-d][1,5]benzothiazepines toward Mitochondrial Benzodiazepine Receptors.J.Med.Chem.1995,38,4730-4738.
(c)Greco,G.;Novellino,E.;Fiorini,I.;Nacci,V.;Campiani,G.;Ciani,S.M.;Garofalo,A.;Bernasconi,P.;Mennini,T.A Comparative Molecular Field Analysis Model for 6-Arylpyrrolo[2,1-d][1,5]benzothiazepines Binding Selectively to the Mitochondrial Benzodiazepine Receptor.J.Med.Chem.1994,37,4100-4108.
76.Hirozumi Inoue,Mikihiko Konda,Tomiki Hashiyama,Hisao Otsuka,Kaoru Takahashi,Mitsunori Gaino,Tadamasa Date,Keiichi Aoe,Mikio Takeda,Sakae Murata,Hiroshi Narita,Taku Nagao.Synthesis of halogen-substituted 1,5-benzothiazepine derivatives and their vasodilating and hypotensive activities.J.Med.Chem.1991,34,675-687.
77.Campiani,G.;Fiorini,I.;De Filippis,M.P.;Ciani,S.M.;Garofalo,A.;Nacci,V.;Giorgi,G.;Sega,A.;Botta,M.;Chiarini,A.;Budriesi,R.;Bruni,G.;Romeo,M.R.;Manzoni,C.;Mennini,T.Cardiovascular Characterization of Pyrrolo[2,1-d][1,5]benzothiazepine Derivatives Binding Selectively to the Peripheral-Type Benzodiazepine Receptor(PBR):From Dual PBR Affinity and Calcium Antagonist Activity to Novel and Selective Calcium Entry Blockers.J.Med.Chem.1996,39,2921-2938.
78.(a)Amblard,M.;Bedos,P.;Olivier,C.;Daffix,I.;Luccarini,J.-M.;Dodey,P.;Pruneau,D.;Paquet,J.-L.;Marti nez,J.Synthesis and Biological Evaluation of Bradykinin B1/B2and Selcctive B1 Receptor Antagonists.J.Med.Chem.2000,43,2381-2386.
(b)Bedos, P.; Amblard, M.; Subra, G.; Dodey, P.; Luccarini, J.-M.; Paquet, J.-L.; Pruneau, D.; Aumelas, A.; Martinez, J. A Rational Approach to the Design and Synthesis of a New Bradykinin B1 Receptor Antagonist. J. Med. Chem. 2000, 43, 2387-2394.
(c) Amblard, M.; Daffix, I.; Berge, G.; Calmes, M.; Dodey, P.; Pruneau, D.; Paquet, J.-L.; Luccarini, J.-M.; Belichard, P.; Martinez, J. Synthesis and Characterization of Bradykinin B2 Receptor Agonists Containing Constrained Dipeptide Mimics. J. Med. Chem. 1999, 42, 4193-4201.
79. (a) Neamati, N.; Turpin, J. A.; Winslow, H. E.; Christensen, J. L.; Williamson, K.; Orr, A.; Rice, W. G.; Pommier, Y.; Garofalo, A.; Brizzi, A.; Campiani, G. Thiazolothiazepine Inhibitors of HIV-1 Integrase. J. Med. Chem. 1999, 42, 3334-3341.
(b) Maruenda, H.; Johnson F. Design and Synthesis of Novel Inhibitors of HIV-1 Reverse Transcriptase. J. Med. Chem. 1995, 38, 2145-2151.
(c) Aiello, F.; Brizzi, A.; Garofalo, A.; Grande, F.; Ragno, G.; Dayam, R.; Neamati, N. Synthesis of novel thiazolothiazepine based HIV-1 integrase inhibitors. Bioorg. Med. Chem. 2004,12, 4459 - 4466.
80. (a) Campiani, G.; Butini, S.; Fattorusso, C.; Catalanotti, B.; Gemma, S.; Nacci, V.; Morelli, E.; Cagnotto, A.; Mereghetti, I.; Mennini, T.; Carli, M.; Minetti, P.; Di Cesare, M. A.; Mastroianni, D.; Scafetta, N.; Galletti, B.; Stasi, M. A.; Castorina, M.; Pacifici, L.; Vertechy, M.; Serio, S. D.; Ghirardi, O.; Tinti, O.; Carminati, P. Pyrrolo[l,3]benzothiazepine-Based Serotonin and Dopamine Receptor Antagonists. Molecular Modeling, Further Structure-Activity Relationship Studies, and Identification of Novel Atypical Antipsychotic Agents. J. Med. Chem. 2004, 47, 143-157.
(b) Campiani, G.; Nacci, V.; Bechelli, S.; Ciani, S. M.; Garofalo, A.; Fiorini, I.; Wikstrom, H.; de Boer, P.; Liao, Y.; Tepper, P. G.; Cagnotto, A.; Mennini, T. New Antipsychotic Agents with Serotonin and Dopamine Antagonist Properties Based on a Pyrrolo[2,1-b][1,3]benzothiazepine Structure. J. Med. Chem. 1998, 41, 3763-3772.
(c) Campiani, G.; Butini, S.; Gemma, S.; Nacci, V.; Fattorusso, C.; Catalanotti, B.; Giorgi, G.; Cagnotto, A.; Goegan, M.; Mennini, T.; Minetti, P.; Di Cesare, M. A.; Mastroianni, D.; Scafetta, N.; Galletti, B.; Stasi, M. A.; Castorina, M.; Pacifici, L.; Ghirardi, O.; Tinti, O.; Carminati, P. Pyrrolo[l,3]benzothiazepine-Based Atypical Antipsychotic Agents. Synthesis, Structure-Activity Relationship, Molecular Modeling, and Biological Studies. J. Med. Chem. 2002, 45, 344-359.
(d) Warawa, E. J.; Migler, B. M.; Ohnmacht, C. J.; Needles, A. L.; Gatos, G. C.; McLaren, F. M.; Nelson, C. L.; Kirkland, K. M. Behavioral Approach to Nondyskinetic Dopamine Antagonists: Identification of Seroquel. J. Med. Chem. 2001, 44, 371-389. (e) Mouithys-Mickalad, A.; Kauffmann, J.-M.; Petit, C.; Bruhwyler,J.;Liao,Y.;Wikstrom,H.;Damas,J.;Delarge,J.;Deby-Dupont,G.;Geczy,J.;Liegeois,J.-F.Electrooxidation Potential as a Tool in the Early Screening for New Safer Clozapine-like Analogues.J.Med.Chem.2001,44,769-776.
(f)Liao,Y.;Venhuis,B.J.;Rodenhuis,N.;Timmerman,W.;Wikstrom,H.;Meier,E.;Bartoszyk,G.D.;Bottcher,H.;Seyfried,C.A.;Sundell,S.New(Sulfonyloxy)piperazinyldibenzazepines as Potential Atypical Antipsychotics:Chemistry and Pharmacological Evaluation.J.Med.Chem.1999,42(12);2235-2244.
81.(a)Effland,R.C.;Davis,L.J.Heterocycl.Chem.1996,33,2055.
(b)Davis,F.A.;Andemichal,Y.W.Tetrahedron Lett.1998,39,3099.
(b)Jeong,I.Y.;Nagao,Y.Tetrahedron Lett.1998,39,8677.
(c)Dietrich,A.;Volmer,A.;Bashir,M.Anal.Chem.1997,69,4143.
(d)Charisson,P.S.Phamrmacological effects of tetrahydroisoquinoline derivatives.Drugs Furure,1989,14,1179.
82.Chen,Y.-H.;Zhang,Y.-H.;Zhang,H.-J.;Liu,D.-Z.;Gu,M.;Li,J.-Y.;Wu,E;Zhu,X.-Z.;Li,J.;Nan,F.-J.Design,Synthesis,and Biological Evaluation of Isoquinoline-1,3,4-trione Derivatives as Potent Caspase-3 Inhibitors.J.Med.Chem.2006,49,1613-1623.
83.Trotter,B.W.;Nanda,K.K.;Kerr,N.R.;Regan,C.R;Lynch,J.J.;Stump,G.L.;Kiss,L.;Wang,J.;Spencer,R.H.;Kane,S.A.;White,R.B.;Zhang,R.;Anderson,K.D.;Liverton,N.J.;McIntyre,C.J.;Beshore,D.C.;Hartman,G.D.;Dinsmore,C.J.Design and Synthesis of Novel Isoquinoline-3-nitriles as Orally Bioavailable Kv1.5 Antagonists for the Treatment of Atrial Fibrillation.J.Med.Chem.2006,49,6954-6957.
84.Perner,R.J.;DiDomenico,S.;Koenig,J.R.;Gomtsyan,A.;Bayburt,E.K.;Schmidt,R.G.;Drizin,I.;Zheng,G.Z.;Turner,S.C.;Jinkerson,T.;Brown,B.S.;Keddy,R.G.;Lukin,K.;McDonald,H.A.;Honore,P.;Mikusa,J.;Marsh,K.C.;Wetter,J.M.;St.George,K.;Jarvis,M.F.;Faltynek,C.R.;Lee,C.-H.In Vitro Structure-Activity Relationship and In Vivo Characterization of 1-(Aryl)-3-(4-(amino)benzyl)urea Transient Receptor Potential Vanilloid 1 Antagonists.J.Med.Chem.2007,50,3651-3660.
85.(a)van Muijlwijk-Koezen,J.E.;Timmerman,H.;Link,R.;van der Goot,H.;IJzerman,A.P.A Novel Class of Adenosine A3 Receptor Ligands.1.3-(1-Pyridinyl)isoquinoline Derivatives.J.Med.Chem.1998,41,3987-3993.
(b)van Muijlwijk-Koezen,J.E.;Timmerman,H.;Link,R.;van der Goot,H.;IJzerman,A.P A Novel Class of Adenosine A3 Receptor Ligands.2.Structure Affinity Profile of a Series of Isoquinoline and Quinazoline Compounds.J.Med.Chem.1998,41,3994-4000.
86.Van Quaquebeke,E.;Mahieu,T.;Dumont,R;Dewelle,J.;Ribaucour,F.;Simon,G.;Sauvage,S.;Gaussin,J.-F.;Tuti,J.;El Yazidi,M.;Van Vynckt,F.;Mijatovic,T.;Lefranc,F.;Darro,F.;Kiss,R.2,2,1-Trichloro-N-({1-[1-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}carbamoyl)acetamide(UNBS3157),a Novel Nonhematotoxic Naphthalimide Derivative with Potent Antitumor Activity.J.Med.Chem.2007,50,4121-4134.
87.(a)Li,D.;Zhao,B.;Sim,S.;Li,T.;Liu,A.;Liu,L.F.;LaVoie,E.J.8,9-Methylenedioxybenzo[i]phenanthridines:Topoisomerase I-Targeting activity and cytotoxicity.Bioorg.Med.Chem.2003,11,3795-3805.
(b)Li,D.;Zhao,B.;Sim,S.;Li,T.;Liu,A.;Liu,L.F.;LaVoie,E.J.2,3-Dimethoxybenzo[i]phenanthridines:topoisomerase I-targeting anticancer agents.Bioorg.Med.Chem.2003,11,521-528.
(c)Makhey,D.;Li,D.;Zhao,B.;Sim,S.;Li,T.;Liu,A.;Liu,L.F.;LaVoie,E.J,Substituted benzo[i]phenanthridines as mammalian topoisomerase-Targeting agents.Bioorg Med.Chem.2003,11,1809-1820.
88.(a)Strumberg,D.;Pommier,Y.;Paull,K.;Jayaraman,M.;Nagafuji,R;Cushman,M.Synthesis of Cytotoxic Indenoisoquinoline Topoisomerase I Poisons.J.Med.Chem.1999,42,446-457.
(b)Xiao,X.;Antony,S.;Pommier,Y.;Cushman,M.On the Binding of Indeno[l,1-c]isoquinolines in the DNA-Topoisomerase I Cleavage Complex.J.Med.Chem.2005,48,3231-3238.
(c)Morrell,A.;Antony,S.;Kohlhagen,G.;Pommier,Y.;Cushman,M.A Systematic Study of Nitrated Indenoisoquinolines Reveals a Potent Topoisomerase I Inhibitor.J.Med.Chem.2006,49,7740-7753.
(d)Morrell,A.;Placzek,M.;Parmley,S.;Grella,B.;Antony,S.;Pommier,Y.;Cushman,M.Optimization of the Indenone Ring of Indenoisoquinoline Topoisomerase I Inhibitors.J.Med.Chem.2007,50,4388-4404.
89.Griffin,R.J.;Fontana,G.;Golding,B.T.;Guiard,S.;Hardcastle,I.R.;Leahy,J.J.J.;Martin,N.;Richardson,C.;Rigoreau,L.;Stockley,M.;Smith,G.C.M.Selective Benzopyranone and Pyrimido[2,1-a]isoquinolin-4-one Inhibitors of DNA-Dependent Protein Kinase:Synthesis,Structure-Activity Studies,and Radiosensitization of a Human Tumor Cell Line in Vitro.J.Med.Chem.2005,48,569-585.
90.Chao,Q.;Deng,L.;Shih,H.;Leoni,L.M.;Genini,D.;Carson,D.A.;Cottam,H.B.Substituted Isoquinolines and Quinazolines as Potential Antiinflammatory Agents.Synthesis and Biological Evaluation of Inhibitors of Tumor Necrosis Factor.J.Med.Chem.1999,42,3860-3873.
91.Orjales,A.;Mosquera,R.;Toledo,A.;Pumar,M.C.;Garcia,N.;Cortizo,L.;Labeaga,L.;Innerarity,A.Syntheses and Binding Studies of New[(Aryl)(aryloxy)methyl]piperidine Derivatives and Related Compounds as Potential Antidepressant Drugs with High Affinity for Serotonin(5-HT)and Norepinephrine(NE)Transporters.J.Med.Chem.2003,46,5511-5532.
92.Salah M.Sami,Robert T.Dorr,David S.Alberts,William A.Remers.1-Substituted 1,1-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones.A new class of antitumor agent.J.Med.Chem.1993,36,765-770.
93.Reinhard,A.;Schneider,Martin.R.;Angerer,S.V.Indolo[2,1-a]isoquinolines.Syntheses,steroid hormone receptor binding affinities,and cytostatic activity.J.Med.Chem.1990,33,153-160.
94.程轩轩,王冬梅,杨得坡.异喹啉类生物碱的生物活性和构效关系研究进展 中草药,2006,37,1900-1904.
95.Ma,W.G.;Fukushi,Y.;Tahara,S.Fungitoxic alkaloids from Hokkaido Corydalis species.Fitoterapia,1999,70,258-265.
96.刘绪文.孙云廷.罂粟碱的临床及药理作用研究进展.中国药物与临床.2006,6,697-299
97.Cho,W.J.;Park,M.J.;Chung,B.H.;Lee,C.O.Synthesis and biological evaluation of 3-arylisoquinolines as antitumor agents.Bioorg.Med.Chem.Lett.1998,8,41-46.
98.Iwassa,K.;Moriyasu,M.;Tachibana,Y.;Kim,H.S.;Wataya,Y.;Wiegrebe,W.;Bastow,K.F.;Cosentino,L.M.;Kozuka,M.;Lee,K.H.Simple isoquinoline and benzylisoquinoline alkaloids potential antimicrobial,antimalarial,cytotoxic,and anti-HIV agents.Bioorg.Med.Chem.2001,9,2871-2884.
99.Greenlee,W.J.;Woodward,R.B.Total synthesis of marasmic acid.J.Am.Chem.Soc.1976,98,6075-6076.
100.张群英,贺广远,吴晓东.四氢小蘖碱的抗心律失常作用.中国药理学通报,1991,6,459-461.
101.邓哲明.活血化瘀中草药之生物活性评估.J.Chin.Med.2004,15,125-136.
102.Bischler A.,Napierslski B.Ber.,1893,26,1903.
103.(a)Sotomayer,N.;Dominguez,E.;Lete,E.Bischler-Napieralski Cyclization-N/C-Alkylation Sequences for the Construction of Isoquinoline Alkaloids.Synthesis of Protoberberines and Benzo[c]phenanthridines via C-2'-Functionalized 3-Arylisoquinolines.J.Org.Chem.1996,61,4062-4072.
(b)Heaney,H.;Shuhaibar,K.F.;Slawin,A.M.Z.Tetrahedron Lett.1996,37,4275;
(c)Banwell,M.G.;Bissett,B.D.; Busato,S.;Cowden,C.J.;Hockless,D.C.R.;Holman,J.W.;Read,R.W.;Wu,A.W.J.Chem.Soc.,Chem.Commun.1995,255;
(d)Siegfried,M.-A.;Hilpert,H.;Rey,M.;Dreiding,A.S.Helv.Chim.Acta 1980,63,938.
104.(a)Manske R.H.The Chemistry of Isoquinolines.Chem.Rev.,1942,30,145-158.
(b)Bergstrom,F.W.Heterocyclic Nitrogen Compounds.Part ⅡA.Hexacyclic Compounds:Pyridine,Quinoline,and Isoquinoline.Chem.Rev.1944,35,77-277.
(c)W.M.Whaley,Org.Reactions,1951,6,75-150.
(d)Thyagarajan,B.S.The Chemistry of Quinolizines.Chem.Rev.1954,54,1019-1064.
(e)Herz,W.;Tocker,S.Furano(3,2-c)pyridines.J.Am.Chem.Soc.1955,77,3554-3556.
(f)Hey,D.H.;Paluel,A.L.The aporphine series.Part Ⅱ.Application of the Bischler-Napieralski reaction to 2-nitrophenyl-N-phenethylacetamides.J.Chem.Soc.1956,4123-4129.
105.Harwood,H.J.;Johnson,T.B.Isoquinoline Derivatives J.Am.Chem.Soc.1933,55,2555-2559.
106.Whaley,W.M.;Hartung,W.H.J.Synthesis of isoquinoline derivatives.Org Chem.1949,14,650-654.
107.Judeh,Z.M.A.;Ching,C.B.;Bu,J.;McCluskey,A.The first Bischler-Napieralski cyclization in a room temperature ionic liquid.Tetrahedron Lett.2002,43,5089-5091.
108.Chern,M.-S.;Li,W.-R.Solid-phase synthesis of isoquinolinones using Bischler-Napieralski cyclization.Tetrahedron Lett.2004,45,8323-8326.
109.(a)Bischler,A.;Napieralski,B.Chem.Ber.1893,26,1891-1903;
(b)Whaley,W.M.;Govindachari,T.R.The Preparation of 3,4-Dihydroisoquinolines and Related Compounds by the Bischler-Napieralski ReactionAdams,R.,Ed.;Organic Reactions;John Wiley andSons.New York,1951;Vol.Ⅵ,pp 74-150;
(c)Tseng,C.K.;Simone,R.A.;Walke,F.H.J.Org.Chem.1973,38,1746-1747;
(d)Fodor,G.;Nagubandi,S.Tetrahedron 1980,36,1279-1300,and references cited therein
110.Spaggiari A,Davoli P,Blaszczak LC,Prati F Spaggiari A,Davoli P,Blaszczak LC,Prati F Synlett 2005,4,661-663.
111.Chakrabarti,Sriparna;Panda,Kausik;Ila,Hiriyakkanavar;Junjappa,Hiriyakkanavar Synthesis of Functionalized 1,2,3,4-Tetrahydro-β-carboline Derived Enamines through Bischler-Napieralski Type Cyclization of Polarized Ketene N,S-Acetals Synlett.2005,2,309-313.
112.(a)Weiping Zheng,Victor I.Nikulin,Anish A.Konkar,Sandeep S.Vansal,Gamal Shams,Dennis R.Feller,Duane D.Miller 2-Amino-4-benzyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridines:Novel Selective 3-Adrenoceptor Agonists J.Med.Chem.1999,42,2287-2294.(b)Paul J.Reider,and Ichiro Shinkai A Modified Bischler-Napieralski Procedure for the Synthesis of 3-Aryl-3,4-dihydroisoquinolines J.Org.Chem.1991,56,6034-6038
113.Angela L.Marquart,Brent L.Podlogar,Edward W.Huber,David A.Demeter,Norton P.Peet,Herschel J.R.Weintraub,Michael R.Angelastro Synthesis of C hiral Hydroxylated Quinolizidines via Vinylogous Bischler-Napieralski Nitrilium Ion Cyclizations J.Org.Chem.1994,59,2092-2100.
114.Churruca,F.;SanMartin,R.;Carril,M.;Urtiaga,M.K.;Solans,X.;Tellitu,I.;Dominguez,E.Direct,Two-Step Synthetic Pathway to Novel Dibenzo[a,c]phenanthridines.J.Org.Chem.2005,70,3178-3187.
115.(a)Sugasawa,S.;Tachikawa,R.Extension of Bischler-Napieralski reaction—Ⅰ:Synthesis of isoquinoline derivatives:A synthesis of rac.-apomorphine dimethyl ether.Tetrahedron,1958,4,205-212.
(b)Sugasawa,S.;Ushioda,S.Extension of the Bischler-Napieralski reaction—Ⅱ:Synthesis ofpyrroline derivatives.Tetrahedron,1959,5,48-52.
(c)Itoh,N.;Sugasawa,S.Bischler-napieralski reaction—Ⅱ:Synthesis of some ketonic isoquinolines.Tetrahedron,1959,6,16-20.
(d)Fujisawa,T.;Sugasawa,S.Extension of Bischler-Napieralski reaction—Ⅳ:Synthesis of some pyridine derivatives.Tetrahedron,1959,7,185-188.
(e)Itoh,N.;Sugasawa,S.Bischler-napieralski reaction—Ⅱ:Synthesis of some ketonic isoquinolines.Tetrahedron Lett.1959,1,24-25.
(f)Morrison,C.G.;Cetenko,W.;Shavel Jr.,J.The Bischler-Napieralski Cyclization of an Imide.J.Org.Chem.1964,29,2771-2772.
(g)Gal,J.;Weinkam,R.J.;Castagnoli Jr.N.Synthesis of cis- and trans-1-(3,4-dimethoxybenzyl)-3,7-dimethyl-5,8-dimethoxy-1,2,3,4-tetrahydroxyisoquin oline.Mechanism of the Bischler-Napieralski reaction.J.Org.Chem.,1974,39,418-421.
116.Wada,Y.;Kaga,H.;Uchiito,S.;Kumazawa,E.;Tomiki,M.;Onozaki,Y.;Kurono,N.;Tokuda,M.;Ohkuma,T.;Orito,K.On the Synthesis of Protopine Alkaloids J.Org.Chem.,2007,72,7301 -7306.
117.Desmaele,D.;Mekouar,K.;d'Angelo,J.Stereocontrolled Elaboration of Quaternary Carbon Centers through the Asymmetric Michael-Type Alkylation of Chiral Imines/Secondary Enamines:Enantioselective Synthesis of(+)-Vincamine.J.Org.Chem.1997,62,3890-3901.
118.Quirante,J.;Escolano,C.;Merino,A.;Bonjoch,J.First Total Synthesis of (±)-Melinonine-E and(±)-Strychnoxanthine Using a Radical Cyclization Process as the Core Ring-Forming Step.J.Org.Chem.1998,63,968-976.
119.Bergmeier,S.C.;Seth,P.P.Aziridine-Allylsilane-Mediated Total Synthesis of (-)-Yohimbane.J.Org.Chem.1999,64,3237-3243.
120.Banwell,M.G.;Harvey,J.E.;Hockless,D.C.R.;Wu,A.W.Electrocyclic Ring-Opening/-Allyl Cation Cyclization Reaction Sequences Involving gem-Dihalocyclopropanes as Substrates:Application to Syntheses of(±)-,(+)-,and (-)-Lycorane.J.Org.Chem.2000,65,4241-4250.
121.Wang,Y.-C.;Georghiou,P.E.First Enantioselective Total Synthesis of(-)-Tejedine.Org.Lett.2002,4,2675-2678.
122.Gurjar,M.K.;Pramanik,C.;Bhattasali,D.;Ramana,C.V.;Mohapatra,D.K.Total Syntheses of Schulzeines B and C.J.Org.Chem.2007,72,6591- 6594.
123.Brodrick,C.I.;Nicholson,J.S.;Short,W.E Heterocyclic derivatives of 1:2-5:6-dibenzocyclohepta- 1:3:5-triene.Part Ⅱ.5-Aryl-2:3-6:7-dibenzo-1-thia-4-azacyclohepta-2:4:6-trienes and their 1:1-dioxides.J.Chem.Soc.1954,3857-3966.
124.Hunziker,F.;Kunzle,F.;Schindler,O.;Schmutz,J.Dibenzo-azepine,-diazepine,-Oxazepine und -thiazepine.3.Mitteilung tiber siebengliedrige Heterocyclen.Helv.Chim.Acta.1964,47,1163-1172.
125.Jarrett,A.D.;Loudon,J.D.Extrusion of sulphur.Part Ⅱ.A new route to phenanthridine derivatives.J.Chem.Soc.1957,3818-3823.
126.(a)Gait,R.H.B.;Loudon,J.D.;Sloan,A.D.B.Extrusion of sulphur.Part Ⅲ.Polycyclic 1:4-thiazepines.J.Chem.Soc.1958,1588-1592.
(b)Gait,R.H.B.;Loudon,J.D.Extrusion of sulphur.Part Ⅳ.Effect of substituents in 11-phenyldibenzo[b,f]-1:4-thiazepine.J.Chem.Soc.1959,885-889.
127.Le Roux,J-R;Desbene,P-L.;Seguin,M.Rearrangement thermiques et photochimiques d'azides d'alkyles tertiaires synthese de dibenzo(b,f)heteroazepines-1,4 et de 11H-dibenzo(b,e)azepinone-11.Tetrahedron Lett.1976,17,3141-3144.
128.Fujii,T.;Hap,W.;Yoshimura,T.New method for the preparation of dibenzo[b,f][1,4]thiazepines.Heteroatom Chemistry 2004,15,246-250.
129.Abd El Latif FM An improved synthesis of pyrazolo[3,4-b][1,5]benzoxazepine,-benzothiazepine and -benzodiazepine derivatives via a convenient one-pot synthesis.J.Heterocycl.Chem.2000,37,1659-1662.
130.Ahmad R,Zia-ul-Haq M,Hameed S,Akhtar H,Duddeck H An unexpected synthesis of novel oxygen-bridged 1,5-benzothiazepine derivatives and their reductive five-membered-ring opening.Monatshefte Fur Chemie 2000,131,393-400.
131.Sathunuru R,Koh B,Zhang HM,Biehl E One-pot synthesis of trans-7-aryl-6H-6a,7-dihydro[1]benzopyrano[3,4-c][1,5]benzothiazepines Heterocycl.2005,65,2493-2503.
132.(a)Ding,H.;Zhang,Y.;Bian,M.;Yao,W.;Ma,C.Concise Assembly of Highly Substituted Furan-Fused 1,4-Thiazepines and Their Diels-Alder Reactions with Benzynes J.Org.Chem.2005,73,578-584.
(b)Ma,C.;Ding,H.;Zhang,Y.;Bian,M.A Ring-Expansion Methodology Involving Multicomponent Reactions:Highly Efficient Access to Polysubstituted Furan-Fused 1,4-Thiazepine Derivatives.Angrew.Chem.,Int.Ed.2006,45,7793-7797.
133.Safonova,T.S.;Nemeryuk,M.P.;Grineva,N.A.;Kermov,M.A.;Likhovidova,M.M.Reactions of 5-amino-6-mercaptopyrimidines with derivatives of p-chloronitrobenzene.synthesis of a new heterocyclic system-pyrimido[4,5-b]-1,4-benzothiazepine.Chem.Heterocycl.Compd.(Engl.Transl.)2001,37,245-250.
134.(a)Yang,J.;Dang,Q.;Liu,J.;Wei,Z.;Wu,J.;Bai,X.Preparation of a Fully Substituted Purine Library J.Comb.Chem.2005,7,474-482.
(b)Liu,J.;Dang,Q.;Wei,Z.;Shi,F.;Bai,X.An Efficient and Regiospecific Strategy to N7-Substituted Purines and Its Application to a Library of Trisubstituted Purines J.Comb.Chem.2006,8,410-416.
(c)Liu,J.;Dang,Q.;Wei,Z.;Zhang,H.;Bai,X.Parallel Solution-Phase Synthesis of a 2,6,8,9-Tetrasubstituted Purine Library via a Sulfur Intermediate J.Comb.Chem.2005,7,627-636.
135.Yang,J.;Che,X.;Dang,Q.;Wei,Z.;Gao,S.;Bai,X.Synthesis of Tricyclic 4-Chloro-pyrimido[4,5-b][1,4]benzodiazepines Org.Lett.2005,7,1541-1543.
136.(a)Che,X.;Zheng,L.;Dang,Q.;Bai,X.Synthesis of novel tricyclic pyrimidine-fused 5,6-dihydrobenzodiazepines via a Pictet-Spengler-like cyclization Tetrahedron,2006,62,2563-2568.
137.(b)Zheng,L.;Xiang,J.;Dang,Q.;Guo,S.;Bai,X.Novel Heterocyclic Scaffold Consisting of Indole-Fused Pteridines J.Comb.Chem.2005;7;813-815.
(c)Zheng,L.;Xiang,J.;Dang,Q.;Guo,S.;Bai,X.Design and Synthesis of a Tetracyclic Pyrimidine-Fused Benzodiazepine Library J.Comb.Chem.2006,8,381-387.
1.(a)Fodor,G.;Nagubandi,S..Correlation of the von Braun,Ritter,Bischler-Napieralski,Beckmann and Schmidt reactions via nitrilium salt intermediates.Tetrahedron 1980,36,1279-1300.
(b)Falco,E.A.;Elion,G.B.;Burgi,E.;Hitchings,G.H.Studies on Condensed Pyrimidine Systems.X.Some 1,3-Oxazolo(5,4-d)pyrimidines.J.Am.Chem.Soc.1952,74,4897-4902.
2.Vyas,G.N.;Shah,N.M.Quinacetophenone monomethyl ether.Org.Syn,Coll.Vol.4,836-838;Vol.31,90-93.
3.(a)Chen,Y.;Evarts,J.B.,Jr.;Torres,E.;Fuchs,R L.Synthesis of Termini-Differentiated 6-Carbon Stereotetrads:An Aikylative Oxidation Strategy for Preparation of the C21-C26 Segment of Apoptolidin.Org.Lett.2002,4,3571-3574.
(b)Kuhler,T.C.;Fryklund,J.;Bergman,N.;Weilitz,J.;Lee,A.;Larsson,H.Structure-Activity Relationship of Omeprazole and Analogs as Helicobacter pylori Urease Inhibitors.J.Med.Chem.1995,38,4906-4916.
4.(a)Lee,D.;Sello,J.K.;Schreiber,S.L.A Strategy for Macrocyclic Ring Closure and Functionalization Aimed toward Split-Pool Syntheses.J.Am.Chem.Soc.1999,121,10648-10649.
(b)Vedejs,E.;Galante,R.J.;Goekjian,P.G.A Thio-Diels-Alder Route to the Azocine Ring System.Total Synthesis of(±)-Otonecine.J.Am.Chem.Soc.1998,120,3613-3622.
(c)Ma,D.;Tang,G.;Kozikowski,A.P.Synthesis of 7-Substituted Benzolactam-V8s and Their Selectivity for Protein Kinase C Isozymes.Org.Lett.2002,4,2377-2380.
(d)Stark,D.;Witt,M.;Oketch-Rabah,H.A.;Jaroszewski,J.W.A New Class of Spermidine-Derived Alkaloids.Org.Lett.2003,5,2793-2796.
(e)Spring,D.R.;Krishnan,S.;Schreiber,S.L.Towards Diversity-Oriented,Stereoselective Syntheses of Biaryl-or Bis(aryl)metal-Containing Medium Rings.J.Am.Chem.Soc.2000,122,5656-5657.
(f)Spring,D.R.;Krishnan,S.;Blackwell,H.E.;Schreiber,S.L.Diversity-Oriented Synthesis of Biaryl-Containing Medium Rings Using a One Bead/One Stock Solution Platform.J.Am.Chem.Soc.2002,124,1354-1363.
(g)Krishnan,S.;Schreiber,S.L.Syntheses of Stereochemically Diverse Nine-Membered Ring-Containing Biaryls.Org.Lett.2004,6,4021-4024.
(h)Illuminati,G.;Mandolini,L.Ring closure reactions of bifunctional chain molecules.Acc.Chem.Res.1981,14,95-102.
1.Stark,B.P.;Duke,A.J.Extrusion Reactions,Pergamon,Oxford,1967.
2.March,J.Advanced Organic Chemistry,3rd Ed.Wiley,New York,1985,937-941.
3.(a)Engel,P.S.;Mechanism of the thermal and photochemical decomposition of azoalkanes.Chem.Rev.1980,80,99-150.
(b)Engel,P.S.;Nalepa,C.J.Photochemical decomposition and isomerization of aliphatic azo compounds.Pure Appl.Chem.1980,52,2621.
(c)Engel,P.S.;Gerth,D.B.Thermolysis of acyclic azoalkanes:simultaneous or stepwise carbon-nitrogen homolysis? J.Am.Chem.Soc.1983,105,6849.
4.Paine,A.J.;Warkentin,J.A relative extrusibility scale and its application to the thermal fragmentation patterns of 5-membered ring diazenes.Can.J.Chem.1981,59,491-505.
5.Maier,G;Pfriem,S;Schafer,U;Matusch,R.Tetra-tert-butyltetrahedrane.Angew.Chem.Int.Ed.Engl.1978,17,520.
6.Cava,M.P.;Schlessinger,R.H.and Van Meter,J.P.The Photolytic Decomposition of Some Sulfones by an Internally Sensitized Path.J.Am.Chem.Soc.1964,86,3173.
7.Cava,M.P.;Mangold,D.1,2-diphenylphenanthro[1]cyclobutadiene:A highly unstable condensed aromatic cyclobutadiene.Tetrahedron Lett.1964,5,1751.
8.Garcia Ruano,J.L.;Alonso de Diego,S.A.;Martin,M.R.;Torrente,E.;Martin Castro,A.M.Efficient Synthesis of Enantiomerically Pure -Alkyl Cyclopropanecarbonitrile Derivatives from Pyrazolines.Org.Lett.2004,6,4945-4948.
9.Chetcuti,P.A.;Knobler,C.B.;Hawthorne,M.F.Intramolecular conversion of a five-membered iridacycle to a three-membered counterpart by carbon dioxide extrusion.Organomet.1986,5,1913-1914.
10.(a)Guziec,F.S.,Jr.;SanFilippo,L.J.Synthetically useful extrusion reactions of organic sulfur,selenium and tellurium compounds.Tetrahedron 1988,44,6241.
(b)Guziec,F.S.,Jr.;SanFilippo,L.J.;Murphy,C.J.;Moustakis,C.A.;Cullen,E.R.Selones as intermediates in the preparation of extremely sterically hindered molecules.Tetrahedron 1985,41,4843.
11.Man,Y.M.;Mak,T.C.W.;Wong,H.N.C.Arene synthesis by extrusion reaction.Part 14.Synthesis of benzo-fused tetraphenylenes and crystal structure of a 4:1 clathrate inclusion compound of dibenzo[b,h]tetraphenylene with p-xylene.J.Org.Chem.1990, 55,3214-3221.
12.Adam,W.;Baumgarten;M.;Maas,W.A Hydrocarbon Hexaradical with Three Localized 1,3-Cyclopentanediyl Triplet Diradicals Linked by 1,3,5-Trimethylenebenzene as Ferromagnetic Coupler:Synthesis of the Azoalkane Precursor,Photochemical Generation of the Polyradical,and EPR Characterization of Its Septet-Spin Ground State.J.Am.Chem.Soc.2000,122,6735-6738.
13.Yang,F.;Lin,S.Preparation and Reduction of Hexahydro[2.2]paracyclophane.J.Org.Chem.1997,62,2727-2731.
14.(a)Paquette,L.Organic Reactions 1977,26,1-71.
(b)Block,E.Reactions of Organosulfur Compounds,Academic Press,New York.1978,75-84.
(c)Durst,T.In Comprehensive Organic Chemistry.
(d)Barton,D.H.R.,Ollis,W.D.,Eds.;Pergamon:Oxford,1984,187-190.
15.Corey,E.J.;Block,E.Sulfur-bridged carbocycles.Ⅱ.Extrusion of the sulfur bridge.J.Org.Chem.1969,34,1233-1240.
16.Philips,J.C.;Swisher,J.V.;Haidukewych D.and Morales,O.Chem.Commun.1971,11,22.
17.Chou,T.-S.;Chen,H.-C.;Yang,W,-C.;Li,W.-S.;Chao,I.;Lee,S.-J.Type-Two Intramolecular Diels-Alder Reactions of Pyrazolo-o-quinodimethanes.J.Org.Chem.2000,65,5760-5767.
18.Yunoki,S.;Takimiya,K.;Aso,Y.;Otsubo,T.A One-Pot Tandem Pictet-Spengler-Diels-Alder Synthesis of Apoyohimbines from 3-Carbomethoxy-2-(formylmethyl)-3-sulfolene.Tetrahedron Lett.1997,38,3071-3074.
19.(a)Scott,G.P.A Derivative of a New Sulfur Heterocycle.J.Am.Chem.Soc.1953,75,6332.
(b)Dimroth,K.and Lenke,G.Chem.Ber.1956,89,2608.
20.Konstantinova,L.S.;Obruchnikova,N.V.;Rakitin,O.A.;Rees,C.W.;Torroba,T.Synthesis of N-unsubstituted bis[1,2]dithiolo[1,4]thiazines and bis[1,2]dithiolopyrroles.J.Chem.Sco.Perkin Trans.1,2000,3421-3427.
21.Marques,M.M.B.;Santos,M.M.M.;Lobo,A.M.;Prabhakar,S.A novel synthesis of arcyriaflavin-A via an intramolecular sulfur extrusion reaction.Tetrahedron Lett.2000,41,9835-9838.
22.Pfeiffer,W.;Dilk,E.;Robberg,H.;Langer,P.Synthesis and Reactivity of 3,4-Dimethyl-4H-1,3,4-thiadiazines.Synlett.2003,15,2392-2394.
23.Gajurel,C.L.;Vaidya,S.R.Extrusion of SO from 1,4-dithiin sulfoxides in dimethylsulfoxide.Indian J.Chem.,Sect.B 1980,19,911-912.
(b)Gajurel,C.L.;Vaidya,S.R.;Shrestha,K.B.Studies on thermal decomposition of 1,4-dithiin sulfoxides in benzene and benzene-3,5-lutidine solvent systems.Indian J.Chem.,Sect.B 1984,18,361-362.
(c)Chow,Y.;Tam,J.N.S.;Blier,J.E.;Szmant,H.H.Mechanism of sulfur monoxide extrusion.J.Chem.Soc.,Chem.Commun.1970,23,604-1605.
(d)Axel,C.;Pierre,G.;Cristian,S.Effect of substituent nature on sulfur extrusion reactions in preparation of the pyrido[2,3-b][1,4]thiazepine framework.Phosphorus,Sulfur Silicon,Relat.Elem.1997,122,59-70.
(e)Fodor,L.;MacLean,D.B.Sulfur extrusion from 1,4-benzothiazepines.Formation of 3-aryl-4-carbomethoxyisoquinolines.Can.J.Chem.1987,65,18-20.
(f)London,J.D.;Young,L.B.Extrusion of sulphur.Part Ⅵ.Novel ring-contractions giving pyridazines and pyrazoles.J.Chem.Soc.1963,5496-5502.
24.(a)Baduenga,J.;Lopez-Ortiz,J.F.;Gotor,V.Formation of a novel N-N bond through SO extrusion.Regioselective synthesis of 1,2,6-thiadiazine S-oxides and pyrazoles.J.Chem.Soc.Chem.commun.1984,891-894.
(b)Baduenga,J.;Lopez-Ortiz,J.F.;Tomas,M.;Gotor,V.An unambiguous synthesis of pyrazoles by sulphur extrusion from 1,2,6-thiadiazines.J.Chem.Soc.perkin Trans.I 1981,1891-1895.
25.Maria,C.and Maria,D.R.Asymmetric Synthesis of Isoquinoline Alkaloids Chem.Rev.2004,104,3341-3370.
26.Bischler A.,Napierslski B.Ber.1893,26,1903.
27.Pictet,A.;Spengler,T.Ber.Dtsch.Chem.Ges.1911,44,2030
28.Knorr,L.Ber.Dtsch.Chem.Ges.1883,16,2597.
29.(a)Manske,R.H.The Chemistry of Isoquinolines.Chem.Rev.1942,30,145-158.
(b)F.W.Bergstrom Heterocyclic Nitrogen Compounds.Part ⅡA.Hexacyclic Compounds:Pyridine,Quinoline,and Isoquinoline.Chem.Rev.1944,35,77-277.
30.(a)Guang,X.D.;Richard,C.L.Synthesis of 3,4-Disubstituted Isoquinolines via Palladium-Catalyzed Cross-Coupling of o-(1-Alkynyl)benzaldimines and Organic Halides.Org.Lett.2001,3,4035-4038.
(b)Kevin,R.R.;Richard,C.L:Synthesis of Isoquinolines and Pyridines via Palladium-Catalyzed Iminoannulation of Internal Acetylenes.J Org.Chem.1998,63,5306-5307.
(c)Guang,X.D.;Richard,C.L.Synthesis of 3,4-Disubstituted Isoquinolines via Palladium-Catalyzed Cross-Coupling of 2-(1-Alkynyl)benzaldimines and Organic Hali.J.Org.Chem.2003,68,920-928.
(d)Mori,M.;Wakamatsu,H.;Tonogaki,K.;Fujita,R.;Kitamura,T.;Sato,Y.Synthesis of Isoquinoline Derivatives Using ROM-RCM of Cyclobutene-yne.J.Org.Chem.2005,70,1066-1069.
31.(a)Nair,V.;Sreekanth,A.R.;Abhilash,N.;Bhadbhade,M.M.;Gonnade,R.C.A Novel Three-Component Reaction for the Diastereoselective Synthesis of 2H-Pyrimido[2,1-a]isoquinolines via 1,4-Dipolar Cycloaddition Org.Lett.2002,4,3575-3577.
(b)Xiang,Z.;Luo,T.;Lu,K.;Cui,J.;Shi,X.;Fathi,R.;Chen,J.;Yang,Z.Concise Synthesis of Isoquinoline via the Ugi and Heck Reactions.Org.Lett.2004,6,3155-3158.
32.Alonso,R.;Campos,P.J.;Garcia,B.;Rodriguez,M.A.New Light-Induced Iminyl Radical Cyclization Reactions of Acyloximes to Isoquinolines.Org.Lett.2006,8,3521-3523.
33.Ghorai,B.K.;Jiang,D.;Herndon,J.W.Novel Synthesis of Isoquinolines Using Isobenzofuran-Nitrile Diels-Alder Reactions.Org.Lett.2003,5,4261-4263.
34.(a)Garcia,E.;Arrasate,S.;Lete,E.;Sotomayor,N.Diastereoselective Intramolecular r-Amidoalkylation Reactions of L-DOPA Derivatives.Asymmetric Synthesis of Pyrrolo[2,1-a]isoquinolines.J.Org.Chem.2005,70,10368-10374.
(b)Pawlas,J.;Vedso,P.;Jakobsen,P.;Huusfeldt,P.O.;Begtrup,M.Synthesis of 1-Hydroxy-Substituted Pyrazolo[3,4-c]- and Pyrazolo[4,3-c]quinolines and -isoquinolines from 4- and 5-Aryl-Substituted 1-Benzyloxypyrazoles.J.Org.Chem.2000,65,9001-9006.
35.Gug,F.;Blondel,M.;Desban,N.;Bouaziz,S.;Vierfonda,J.-M.;Galonsa,H.An expeditious synthesis of 6-aminophenanthridines.Tetrahedron Lett.2005,46,3725-3727.
36.Su,S.;Porco,John A.Jr.;Synthesis of Pyrrolo-isoquinolines Related to the Lamellarins Using Silver-Catalyzed Cycloisomerization/Dipolar Cycloaddition.J.Am.Chem.Soc.2007,129,7744-7745.
37.Nair,V.;Sreekanth,A.R.;Abhilash,N.;Bhadbhade,M.M.;Gonnade,R.C.A Novel Three-Component Reaction for the Diastereoselective Synthesis of 2H-Pyrimido[2,1-a]isoquinolines via 1,4-Dipolar Cycloaddition.Org.Lett.2002,4,3575-3577.
38.(a)Jarrett,A.D.;Loudon,J.D.Extrusion of sulphur.Part Ⅱ.A new route to phenanthridine derivatives.J.Chem.Soc.1957,3818-3823.
(c)Galt,R.H.B.;Loudon,J.D.;Sloan,A.D.B.Extrusion of sulphur.Part Ⅲ.Polycyclic 1:4-thiazepinesJ.Chem. Soc. 1958, 1588-1593.
(d) Glat, R. H. B.; Loudon, J. D. Extrusion of sulphur. Part IV. Effect of substituents in 11-phenyldibenzo[b,f]-1: 4- thiazepine. J. Chem. Soc. 1959, 885-889.
39. (a) Masquelin, T.; Obrecht, D. A novel access to 2,4-substituted quinolines from acetylenic ketones. Tetrahedron 1997, 53, 641-646;
(b) Cabarrocas, G.; Rafel, S.; Ventura, M.; Villalgordo. J. M. A New Approach Toward the Stereoselective Synthesis of Novel Quinolyl Glycines: Synthesis of the Enantiomerically Pure Quinolyl-β-Amino Alcohol Precursors. Synlett. 2000, J, 595-598;
(c) Cabarrocas, G.; Ventura, M.; Maestro, M.; Mahia, J.; Villalgordo, J. M. Synthesis of novel optically pure quinolyl-β-amino alcohol derivatives from 2-amino thiophenol and chiral a-acetylenic ketones and their IBX-mediated oxidative cleavage to N-Boc quinolyl carboxamides. Tetrahedron: Asymmetry 2001, 12, 1851-1863.
40. (a) Bradsher, C. K.; McDonald, J. W. Aromatic Nuclei by the Sulfur Extrusion Reaction. I. Phenanthridizinium Derivatives. J. Org. Chem. 1962, 27, 4475-4478.
(b) Bradsher, C. K.; McDonald, J. W. Aromatic Nuclei by the Sulfur Extrusion Reaction. II. 1 Phenanthridizinium Salts with a Substituent in Ring A. J. Org. Chem. 1962, 27, 4478-4481.
(c) Bradsher, C. K.; McDonald, J. W. J. Aromatic Nuclei by the Sulfur Extrusion Reaction. III. 1 New Benzophenanthridizinium Systems. Org. Chem. 1962, 27, 4481-4485.
41. (a) Safonova, T. S.; Nemeryuk, M. P.; Grineva, N. A.; Keremov, A. F.; Anisimova, O. S.; Solov'eva, N. P. Properties and conversions of pyrimido[4,5-b]-1,4-benzothiazepines. synthesis of a novel heterocyclic system: pyrimido[5,4-c]isoquinoline. Chem. Heterocycl. Compd. (Engl. Transl.) 2004, 40, 1609-1617.
(b) Nemeryuk, M. P.; Grineva, N. A.; Safonova, T. S. Derivatives of pyrimido[5,4-c]isoquinoline. Patent U.S.S.R. 1983, 725427.
42. (a) Roth, M.; Dubs, P.; Gottschi, E.; Eschenmoser, A. Helv. Chim. Acta. 1971, 54, 710.
(b) Guziec, F. S.; Sanfilippo, L. J. Synthetically useful extrusion reactions of organic sulfur, selenium and tellurium compounds. Tetrahedron 1988, 44, 6241-6285.
(c) Sakurai, O.; Ogiku, T.; Takahashi, M.; Hayashi, M.; Yamanaha, T.; Horikawa, H.; Iwasaki, T. A New Synthesis of 1-Alkylcarbapenems Utilizing Eschenmoser Sulfide Contraction of the Novel Thiazinone Intermediates. J. Org. Chem. 1996, 61, 7889-7894.
(d) Mitchell, R. H. A novel reaction of α-chlorosulfides. A new synthesis of diarylethylenes (stilbenes). Tetrahedron Lett. 1973, 14, 4395-4398.
(f) Lee, H. K.; Kim, J.; Pak, C. S. Reaction of thioamides with zinc enolate: Synthesis of vinylogous carbamates. Tetrahedron Lett. 1999,40,2173-2174.
43. (a) Dolle, R. E. Comprehensive Survey of Combinatorial Library Synthesis: 2000. J. Comb. Chem. 2001, 3, 477-517.
(b) Franzen, R. G. Recent Advances in the Preparation of Heterocycles on Solid Support: A Review of the Literature. J. Comb. Chem. 2002, 2, 195-214.
(c) Houghten, R. A.; Pinilla, C.; Appel, J. R.; Blondelle, S. E.; Dooley, C. T.; Eichler, J.; Nefzi, A.; Ostresh, J. M. Mixture-Based Synthetic Combinatorial Libraries. J. Med. Chem. 1999, 42, 3743-3778.
(d) Nefzi, A.; Ostresh, J. M.; Houghten, R. A. The Current Status of Heterocyclic Combinatorial Libraries. Chem. Rev. 1997, 97, 449-472.
(e) Thompson, L. A.; Ellman, J. A. Synthesis and Applications of Small Molecule Libraries. Chem. Rev. 1996, 96, 555-600.
(f) Gordon, E. M.; Barret, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. Applications of Combinatorial Technologies to Drug Discovery. 2. Combinatorial Organic Synthesis, Library Screening Strategies, and Future Directions.J. Med. Chem. 1994, 37, 1385-1401.
44. (a) Hua, G.; Woollins, J. D. The syntheses of sulfides by deoxygenation of sulfoxides using Woollins' reagent. Tetrahedron Lett. 2007, 48, 3677-3684.
(b) Iranpoor, N.; Firouzabadi, H.; Shaterian, H. R. A New Approach to the Reduction of Sulfoxides to Sulfides with 1,3-Dithiane in the Presence of Electrophilic Bromine as Catalyst. J. Org. Chem. 2002, 67, 2826-2830.
(c) Lucien, E.; Greer, A. Electrophilic Oxidant Produced in the Photodeoxygenation of 1,2-Benzodiphenylene Sulfoxide. J. Org. Chem. 2001, 66, 4576-4584.
(d) Nicolaou, K. C.; Koumbis, A. E.; Snyder, S. A.; Simonsen, K. B. Novel Reactions Initiated by Titanocene Methylidenes: Deoxygenation of Sulfoxides, N-Oxides, and Selenoxides. Angew. Chem. Int. Ed. 2000, 39, 2529-2533.
(e) Kikuchi, S.; Konishi, H.; Hashimoto, Y. The deoxygenation of sulfoxide mediated by the Ph3P/Lewis acid combination and the application to the kinetic resolution of racemic phosphines using optically active sulfoxide. Tetrahedron 2005, 61, 3587-3591.
(f) Gurria, G. M.; Posner, G. H. Photochemical deoxygenation of aryl sulfoxides. J. Org. Chem. 1973, 38, 2419-2420.
(g) Guindon, Y.; Atkinson, J. G.; Morton, H. E. Deoxygenation of sulfoxides with boron bromide reagents. J. Org. Chem. 1984, 49, 4538-4540.
45. (a) Sakamoto, M.; Yamamoto, K; lsshiki, K.; lshikura, T.; Fukagawa, Y.; Yoshioka, T. Antibacterial activity and chemical modifications of ps-5 at the c-3 side chain. J. Antibiotics 1990, 43, 1254-1270 and references cited therein.
(b) Takemura, M.; Higashi, K.; Fujiwara, H.; Sato, M.; Furukawa, M. Chem. Pharm. Bull. 1986, 34, 1089-1093.
(c) Rao, V. S.; Remillard, R.; Menard, M. antibacterial activity and chemical modifications of ps-5 at the c-3 carbapenem antibiotics: displacement of c-3 sulfur side chain by another thiol moiety, and quatemization of a weaker pyridine nitrogen over a stronger primary amine (preparation of BMY 40732 and BMY 40886)side chain. Heteroatom Chemistry 1992, 3, 25-31.
(d) Oda, K.; Yoshida, A. Side chain substitution reaction of 2-arylsulfinyl and 2-arylsulfonyl intermediates for 1β-methylcarbapenems. Tetrahedron Lett. 1997, 38, 5687-5690.