酰肼聚合物试剂参与的杂环化合物的固相合成
摘要
本论文从酰肼聚合物试剂出发,通过此试剂完成一系列杂环化合物的固相合成。主要包括以下几个方面的内容:
一、直接利用酰肼聚合物试剂进行一些杂环化合物的固相合成:
1、利用酰肼聚合物试剂与双亲电试剂发生分子内串联反应,建立了稠杂环化合物的固相合成方法,并用于腺苷受体拮抗剂类化合物的固相合成中,高产率高纯度的得到了目标产物。
2、酰肼聚合物试剂与异氰酸酯反应,得到中间体树脂,此树脂进一步在碱性条件下环合得到聚合物负载的1,2,4-三唑-3-酮,然后在三氟乙酸/二氯甲烷体系中切断,得到了4,5-二取代的-1,2,4-三唑-3-酮类化合物。
3、酰肼聚合物试剂与羰基化合物反应,得到相应的酰腙树脂,该树脂与亚硫酰氯发生Hurd-Mori型反应,无痕迹切割得到一系列4,5-二取代-1,2,3-噻二唑类化合物,提供了4,5-二取代-1,2,3-噻二唑有效的固相合成方法。
二、从酰肼聚合物试剂出发,通过条件的选择优化,制备了新型的4-氨基-5-巯基-1,2,4-三唑聚合物试剂,以此树脂为合成砌块,建立了相关稠杂环化合物的固相合成方法:
1、该树脂与卤代酮反应,用于制备了均三唑并[3,4-b]-1,3,4-噻二嗪衍生物。
2、与羧酸反应,进行均三唑并[3,4-b]-1,3,4-噻二唑衍生物的固相合成。
以上反应条件温和,目标产物的产率和纯度良好,为组合化学中实现多样性导向的小分子杂环化合物库奠定了基础。
This thesis focuses on the solid phase synthesis of several kinds of heterocyclic compounds from the resin-bound acylhydrazine.The following are the main parts studied in detail:
Firstly,the resin-bound acylhydrazine reagent was directly applied in solid phase organic synthesis of heterocyclic compounds:
1.Dinucleophilic site exists in acylhydrazine,which can undergo tandem reaction with kinds of dielectrophilic reagents.We applied resin-bound acylhydrazine into solid phase organic synthesis of adenosine acceptor inhibitors,and got the pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]-pyrimidines derivatives in good yields and high purities.
2.The resin-bound acylhydrazine was reacted with isocyanates to afford the aroylsemicarbazide resin.Then,the intramolecular cyclization of the resin was carried out in the presence of NaOH(aq.),providing the 1,2,4-triazol-3-one resin after acidified by HCl(aq.).After cleavaged by TFA/DCM,we got the desired compounds.
3.Reaction of acylhydrazines resin with ketone afforded the corresponding support-bound acylhydrazones.After Hurd-Mori type cleavage accomplished using thionyl chloride,many kinds of 1,2,3-thiadiazoles derivatives were efficiently obtained in good yield and high purity via traceless cyclization cleavage of resin-bound acylhydrazones.
Secondly,a novel resin-bound 4-amino-5-mercapto-1,2,4-triazole was prepared from acylhydrazines resin in optimal method.The facile and potent methods for solid phase synthesis of related fuse heterocyclic compounds were provided based on this resin.
1.The resin was reacted with halogenated ketone to afford the 1,2,4-triazolo-[3, 4-b]-[1,3,4]thiadiazine derivatives.
2.Solid phase synthesis of 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives were completed by the reaction of this resin with carboxylic acid.
The reaction conditions presented in this thesis were mild,and the desired products were efficiently obtained in good yield and high purity.This approach could be used to design and synthesize the diversity-oriented small molecule library in combinatorial chemistry.
一、直接利用酰肼聚合物试剂进行一些杂环化合物的固相合成:
1、利用酰肼聚合物试剂与双亲电试剂发生分子内串联反应,建立了稠杂环化合物的固相合成方法,并用于腺苷受体拮抗剂类化合物的固相合成中,高产率高纯度的得到了目标产物。
2、酰肼聚合物试剂与异氰酸酯反应,得到中间体树脂,此树脂进一步在碱性条件下环合得到聚合物负载的1,2,4-三唑-3-酮,然后在三氟乙酸/二氯甲烷体系中切断,得到了4,5-二取代的-1,2,4-三唑-3-酮类化合物。
3、酰肼聚合物试剂与羰基化合物反应,得到相应的酰腙树脂,该树脂与亚硫酰氯发生Hurd-Mori型反应,无痕迹切割得到一系列4,5-二取代-1,2,3-噻二唑类化合物,提供了4,5-二取代-1,2,3-噻二唑有效的固相合成方法。
二、从酰肼聚合物试剂出发,通过条件的选择优化,制备了新型的4-氨基-5-巯基-1,2,4-三唑聚合物试剂,以此树脂为合成砌块,建立了相关稠杂环化合物的固相合成方法:
1、该树脂与卤代酮反应,用于制备了均三唑并[3,4-b]-1,3,4-噻二嗪衍生物。
2、与羧酸反应,进行均三唑并[3,4-b]-1,3,4-噻二唑衍生物的固相合成。
以上反应条件温和,目标产物的产率和纯度良好,为组合化学中实现多样性导向的小分子杂环化合物库奠定了基础。
This thesis focuses on the solid phase synthesis of several kinds of heterocyclic compounds from the resin-bound acylhydrazine.The following are the main parts studied in detail:
Firstly,the resin-bound acylhydrazine reagent was directly applied in solid phase organic synthesis of heterocyclic compounds:
1.Dinucleophilic site exists in acylhydrazine,which can undergo tandem reaction with kinds of dielectrophilic reagents.We applied resin-bound acylhydrazine into solid phase organic synthesis of adenosine acceptor inhibitors,and got the pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]-pyrimidines derivatives in good yields and high purities.
2.The resin-bound acylhydrazine was reacted with isocyanates to afford the aroylsemicarbazide resin.Then,the intramolecular cyclization of the resin was carried out in the presence of NaOH(aq.),providing the 1,2,4-triazol-3-one resin after acidified by HCl(aq.).After cleavaged by TFA/DCM,we got the desired compounds.
3.Reaction of acylhydrazines resin with ketone afforded the corresponding support-bound acylhydrazones.After Hurd-Mori type cleavage accomplished using thionyl chloride,many kinds of 1,2,3-thiadiazoles derivatives were efficiently obtained in good yield and high purity via traceless cyclization cleavage of resin-bound acylhydrazones.
Secondly,a novel resin-bound 4-amino-5-mercapto-1,2,4-triazole was prepared from acylhydrazines resin in optimal method.The facile and potent methods for solid phase synthesis of related fuse heterocyclic compounds were provided based on this resin.
1.The resin was reacted with halogenated ketone to afford the 1,2,4-triazolo-[3, 4-b]-[1,3,4]thiadiazine derivatives.
2.Solid phase synthesis of 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives were completed by the reaction of this resin with carboxylic acid.
The reaction conditions presented in this thesis were mild,and the desired products were efficiently obtained in good yield and high purity.This approach could be used to design and synthesize the diversity-oriented small molecule library in combinatorial chemistry.
引文
1.Hydrazine and Its Derivatives,in Kirk-Othmer Encyclopedia Chemical Technology,4th edn.vol.13,John Wiley & Sons,New York,1995
2.White E.H.;Roswell D.F.Acc.Chem.Res.1970,3(2),54-62.
3.Licandro,E.;Perdicchia,D.Eur.J.Org.Chem.2004,665-675.
4.Hwang,S.W.;Chen,Y.Macromolecules 2002,35(14),5438-5443.
5.Zou,X.J.;Lai,L.H.;Jin,G.Y.J.Agric.Food Chem.2002,50(13),3757-3760.
6.PonticeUo,G.S.;Engelhardt,E.L.;Baldwin,J.J.J.Heterocyclic Chem.1980,17,425-427.
7.Gillet,J.P.Chem.Abstr.1992,117212.
8.刘素燕,惠新平,许鹏飞,张自义,高等学校化学学报,2000,21,1386.
9.Karnik,A.V.;Kamath,R.G.Indian J.Chem.Sect.B 1997,36B,803.
10.Dabiri,M.;Salehi,P.;Baghbanzadeha,M.;Bahramnejada,M.Tetrahedron Lett.2006,47,6983-6986.
11.Firoozi,F.;Javidnia,K.;Karnali,M.J.Heterocyclic Chem.1995,32,123.
12.Sun,X.W.;Hui,X.P.;Chu,C.H.;Zhang,Z.Y.Indian J.Chem.Sect.B 2001,40B,15.
13.Wang,Y.;Sauer,D.R.;Djuric,S.W.Tetrahedron Lett.2006,47,105-108.
14.Coppo,F.T.;Evans,K.A.;Graybill,T.L.;Burton,G.;Tetrahedron Lett.2004,45,3257-3260.
15.Hwang,J.Y.;Choi,H.S.;Lee,D.H.;Gong,Y.D.J.Comb.Chem.2005,7,816-819.
16.Kane,J.M.Synthesis 1987,912
17.Senthilvelan,A.;Thirumalai,D.;Ramakrishnan,V.T.Tetrahedron 2004,60,851.
18.Kane,J.M.;Ogden,A.M.L.Miller,J.A.J.Med.Chem.1994,37,125.
19.Klingele,M.H.;Brooker,S.Eur.J.Org.Chem.2004,3422.
20.Yeung,K.S.;Farkas,M.E.;Kadow,J.F.;Meanwell,N.F.Tetrahedron Lett.2005,46,3429-3432.
21.Carling,R.W.;Moore,K.W.J.Mad.Chem.2004,47,1807.
22.Stocks,M.J.,Cheshire,D.R.,Reynolds,R.Org.Lett.,2004,6,2969.
23.Hordiyenko,O.V.;Biitseva,A.V.;Kornilov,M.Y.;Brosse,N,;Hocquet,A.;Shishkin,O.V.;Zubatyuk,R.I.Eur.J.Org.Chem.2006,2833-2842
24.Ivachtchenko,A.;Kovalenko,S.;Tkachenko,O.V.;Parkhomenko,O.J.Comb.Chem.2004,6,573-583.
25.Okamura,T.;Kurogi,Y.;Hashimoto,K.;Nishikawaa,H.;Nagaob,Y.Bioorg.Med.Chem.Lett.2004,14,2443-2446.
26.Endo,Y.;Uchida,T.;Shudo,K.Tetrahedron Lett.1997,12,2113-2116.
27.Hameurlaine,A.;Abramov,M.A.;Dehaen,W.Tetrahedron Lett.2002,3,1015-1017.
28.Machkhoshvili,R.I.;Shchelokov,R.N.Russ.J.Coord.Chem.2000,26(10),677.
29.Hirsch-Kuchma,M.;Nicholson,T.;Davison,A.;Jones,A.G.J.Chem.Soc.,Dalton Trans.:Inorg.Chem.1997,18,3189.
30.Pickart,L.;Goodwin,W.H.;Murphy,T.B.;Johnson,D.K.J.Cell Biochem.Suppl.1982,6,482.
31.Sorenson,J.R.J.Chem.Ber.1984,20,1110.
32.Odunola,O.;Adeoye,I.;Woods,J.Synth.React.Inorg.Met.-Org.Chem.2002,32(4),801-817;
33.Licandro,E.;Maiorana,S.;Manzotti,R.;Papagni,A.;Perdicchia,D.;Pryce,M.;Tiripicchio,A.;Lanfranchi,M.Chem.Commun.1998,383-384.
34.Chande,M.S.;Kamik,B.M.J.Indian Chem.Soc.1993,70,268.
35.Hui,X.P.;Xu,P.F.;Wang,Q.;Zhang,Q.;Zhang Z.Y.Chin.J.Chem.2001,19,991.
36.Zhang,Z.Y.;Sun,X.W.Heterocycles 1998,48,561.
37.Zhang,Y.;Sun,X.W.;Hui,X.P.;Zhang,Z.Y.;Wang,Q.;Zhang,Q.Chin.Chem.2002,20,168.
38.曹玮,文丽荣,王啸,赵桂龙,李明,山东大学学报(自然科学版),2005,40117-120.
39.Srirupa,S.;Srivastava,B.B.Indian J.Heterocyclic Chem.,2005,15,51-54.
40. Cetin, A. Heterocycles, 2006, 68(9), 1901-1907
41. Wang, X. Chin. J. Org. Chem. 2005, 25(9), 1089-1093.
42. Dai, Z. F,; Zhang Z. Y.; Lanzhou Daxue Xuebao, Ziran Kexueban, 2002, 38(5), 51-57
43. Cartwright, D. D. J.; Clark, B. A. J.; Hamish McNab, H.J. Chem. Soc. Perkin Trans. 1,2001,4,424-428.
44. Invidiata, F. P.; Furno, G.; Lampronti, I.; Simoni, D. J. Heterocyclic Chem. 1997, 34(4), 1255-1258.
45. Goswami, B. N.; Kataky, J. C.; Baruah, J. N.J. Heterocyclic Chem. 1984, 21(4) , 225.
46. Sharma,R.S.; Babel, S. C. J. Indian Chem .Soc. 1982, 59, 877.
47. Gapta, A. S. K.; Misra, H. K. Indian J. Chem. Sect. B 1979,17b(2), 185.
48. Zhang, L. X.; Zhang, Z. Y. Chem. Chin. Univ. 1989,2, 147.
49. Fernandes, P. S.; Sonar, T. M. J. Indian Chem. Soc. 1988, Vol, LXV49.
50. Mohsen, A.; Omar, M. E.; Aboularafa, O. M.J. Heterocyclic Chem. 1986, 23, 1339.
51. Rajive, G.; Satya, P.; Avinash, K. G.; Kachroo, P. L. Indian J. Chem. 1994,33, 888.
52. Swamy, S. N.; Priya, B. S.; Prabhuswamy, B.; Doreswamy, B.H.; Prasad, J. S.; Rangappa, K.S. Eur. J. MedChem. 2006, 41, 531-538.
53. Xu, P. F.; Zhang, Z. H.; Hui, X. P.; Zheng, R. L. J. Chin. Chem. Soc. 2004, 51, 315.
54. Qiao, R. Z; Hui, X. P.; Xu, P. F ; Zhang, Z. Y.; Cheng, D. L. J. Chin. Chem. Soc. 2001, 19, 800.
55. Eisa, H. A.; Emam, A. A.; Moustafa, M. A.; Ashmawy, M. M. J. Chin. Chem. Soc. 1988, 35, 393.
56. Shukurov, S. S.; Kukaniev. M. A.; Bobgaribov, B. M.; Sabirov, S. S. Chem. Abstr. 1996,124, 289363.
57. Sun, X. W.; Hui, X. P.; Chu, C. H.; Zhang, Z. Y. Indian J. Chem. Sect. B 2000, 39B, 779.
58. Zhang, Z. Y.; Chen, X. Chin. J. Chem. 1992,10, 59.
59. Shukurov, S. S.; Kukaniev. M. A. Chem. Abstr. 1996,124, 558565.
60. Zhang, Z. Y.; Chen, X. Chin. J. Chem. 1992,10, 59.
61. Chande, M. S.; Karnik, B. M. J. Indian Chem. Soc. 1993, 70, 268.
62. Mohan, J. ; Anianeylu, G. S. R.Pol. J. Chem. 1987, 61, 547.
63. Sonasekhana, S.; Thakkar, R. K.; Shah, G. F. J. Indian Chem. Soc. 1972, 49, 1057.
64. Samie, Z. K. ; Ashmawi, M. I.; Fattah, B. Egypt J. Pharm. Sci. 1988,29, 251.
65. Sakata, M. ; Shirakawa, Y.; Kamata, N. ; Sakaguchi, Y.; Nishino, H.; Ouyang, J. ; Kurosawa, K. J. Heterocyclic Chem. 2000,37, 269.
66. Bhalerao, U. T. ; Muralikrishna, C. ; Rani, B. R. Tetrahedron 1994, 50, 4019.
67. Samie, Z. K.; Ashmawi, M. I.; Fattah, B. Egypt J. Pharm. Sci. 1988,29, 251.
68. Awad, I. M. A.; Rahman, A. E.; Bakite, E. A.J. Chem. Technol. Biotechnol. 1991, 51, 483.
69. Merrifield, R. B. J. Am. Chem. Soc. 1963, 85, 2149.
70. Recent reviews on SPOS. see: (a) Fruchtel, J. S.; Jung, G. Angew. Chem. Int. Ed. 1996, 35, 17. (b) Lorsbach, B. A.; Kurth, M. J. Chem. Rev. 1999, 99, 1549. (c) Guillier, F.; Orain, D.; Bradley, M.Chem. Rev. 2000,100, 2091. (d) Franzen, R. G. J. Comb. Chem. 2000, 2, 195. (e) Krchnak, V.; Holladay, M. W. Chem. Rev. 2002, 102, (f) Dolle, R. E.; Bourdonnec, B. E.; Morales, G. A.; Moriarty, K. J.; Salvino, J. M. J. Comb. Chem. 2006,8, 597-635.
71. (a) Dolle, R. E. J. Comb. Chem. 2004, 6, 623-679. (b)Kates, S. A.; Albericio, F. Macrcel Dekker, Inc, New York, 2000. (c)Burke, M. D.; Schreiber, S. L. Angew. Chem. Int. Ed. 1996, 43, 46-58.
72. Sahin, G.; Palaska, E.; Ekizoglu, M. Farmaco 2002, 57(2), 101-107.
73．赵金龙,硕士学位论文,浙江大学,杭州,2006．(Zhao, J. L., M. D. Thesis, Zhejiang University, Hangzhou, 2006)
1.Moro,S.;Braiuca,P.;Deflorian,F.;Ferrari,C.;Pastorin,G.;Cacciari,B.;Baraldi,P.B.J.Med.Chem.2005,48,152-162.
2.Baraldi,P.G.;Tabrizi,M.A.;Bovero,A.;Avitabile,B.;Preti,D.;Fruttarolo,F.;Romagnoli,R.;Varani,K.;Borea,P.A.Eur.J.Med.Chem.2003,38,367-382.
3.Baraldi,P.G.;Cacciari,B.;Romagnoli,R.;Spalluto,G.;Monopoli,A.;Ongini,E.;Borea,P.A.J.Med.Chem.2002,45,115-126.
4.Ongini,E.Drug Dev.Res.1997,42,63.
5.Neustadt,B.R.;Hao,J.;Lindo,N.;Greenlee,W.J.;Stamford,A.W.;Tulshian,D.;Ongini,E.;Hunter,J.;Monopoli,A.;Bertorelli,R.;Foster,C.Bioorg.Med.Chem.Lett.2007,17,1376-1380.
6.Baraldi,P.G.;Kashef,H.;Farghaly,A.R.;Vanelle,P.;Fruttarolo,F.Tetrahedron,2004,60,5093-5104.
7.Okamura,Y.;Kurogi,Y.;Hashimoto,K.;Nishikawa,H.;Nagao,Y.Bioorg.Med.Chem.Lett.2004,14,2443-2446.
8.赵金龙,硕士学位论文,浙江大学,杭州,2006.(Zhao,J.L,M D.Thesis,Zhejiang University,Hangzhou,2006)
9.Kane,J.M.;Baron,B.M.;Dudley,M.W.;Sorensen,S.M.;Staeger,M.A.; Miller, F. P. J. Med. Chem. 1990, 33, 2772.
10. Heers, J.; Back, J. J.; Cutsem, J. V. J. Med. Chem. 1984,27, 894.
11. Mullican, M. D.; Wilson, M. W.; Connor, D. T.; Kostlan, C. R.; Schrier, D. J.; Dyer, D. D. J. Med. Chem. 1993,36,1090.
12. Neslihan, D.; Reyhan, U.; Ahmet, D. Bioorg. Med. Chem. 2002,10, 3717.
13. Boschelli, D. H.; Connor, D. T.; Bornemeier, D. A.; Dyer, R. D.; Kennedy, J. A.; Okonkwo, G. C.; Schrier, D. J.; Wright, C. D.J. Med. Chem., 1993,36, 1802.
14. Romine, J. L.; Martin, S. W.; Gribkoff, V. K.; Boissard, C. G.; Dworetzky, S. I.; Natale, J.; Li, Y.; Gao, Q.; Meanwell, N. A.; Starrett, J. E.J. Med. Chem. 2002, 45, 2942.
15. Elipe, M. V. S.; Huskey S. W.; Zhu, B. J. Pharm. Biomed. Anal. 2003, 30, 1431 -1432
16. Xu, Y.; Mayhugh, D.; Saeed, A.; Wang, X.; Thompson, R. C.; Dominianni, S. J.; Kauffman, R. F.; Sing, J. ; Bean, J. S.; Bensch, W. R.; Barr, R. J.; Osborne, J.; Montrose- Rafizadeh, C.; Zink, R. W.; Yumibe, N. P.; Huang, N. D.; Rungta, D.; Maise, D. E.; Mantlo, N. B. J. Med. Chem. 2003, 46, 5121-5124.
17. Hamed, M. O.; Rabet, H.; Efrit, M. L. C. R. Chimie . 2007,10, 1147-1156.
18. Romine, J. L.; Martin, S. W.; Gribkoff, V. K.; Boissard, C. G.; Dworetzky, S.D.; Natale, J.; Li, Y.; Gao, Q.; Meanwell, N. A.; Starrett, J. E. J. Med. Chem. 2002, 45, 2942-2952
19. Bakulev, V. A.; Dehaen, W. "The Chemistry of 1,2,3-Thiadiazoles", in: The Chemistry of Heterocyclic Compounds (Ed.: Taylor, E. C.; Wipf, P.; Weissberger, A.), John Wiley & Sons, Inc., New York, 2004.
20. Katritzky, A. R.; Tymoshenko, D. O.; Nikonov G.N. J. Org. Chem. 2001, 66, 4045-4046.
21. Thomas, E. W.; Nishizawa, E. E.; Zimmermann, D. C.,Williams, D. J. J. Med. Chem. 1985, 28, 442.
22. Babu B. R.; Vaz ,A. D. N. Biochemistry 1997,36, 7209-7216.
23. Rabindranath , T.; Arup, G.; Jasbir, S.,; Edward, R. B., Thelma S. A., Bio.Med. Chem. Lett. 2007, 17, 1793-1798
24. Katritzky, A. R.; Tymoshenko, D. O.; Nikonov G.N. J. Org. Chem. 2001, 66, 4045-4046.
25. Latour, J. M.; Marchon, J. C.; Nakajima, M.J. Am. Chem. Soc. 1979 , 4, 101-114.
26. Katritzky, A. R.; Nikonov, G. N.; Moyano, E. L.; Novruz G. Akhmedov, N.G. ARKIVOC 2003, (vii), 121-138.
27. Rovira, C.; Veciana, J.; Santalb, N.; TarrBs, J.; Cirujeda, J.; Molins, E.;Llorca, J.; Espinosa, E. J. Org. Chem. 1994, 59, 3307-3313.
28.Thomas, E. W. Storr, R. C., Katritzky, A. R., Rees, C. W., Sriven, E. E V., Series Eds.; Pergamon: London, 1996; Vol. 4, p 289.
29.Thomas, E. W. Storr, R. C., Katritzky, A. R., Rees, C. W., Sriven, E. F. V., Series Eds.; Pergamon: London, 1996; Vol. 4, p 447.
30. Hinz, W.; Just, G. Synth. Commun. 1986, 917.
31. Hurd, C. D.; Mori, R. I. J. Am. Chem. Soc, 1955, 77, 5359-5364.
32. Chen, H.; Wang, W. H.; Xue, M.; Cao, R. Z.; Liu, L. Z. Heteroatom Chem. 2000, 11, 413-416.
33. Hu, Y; Baudart, S.; Porco, J. A.J. Org. Chem. 1999, 64, 1049-1051.
1.Cartwright,D.D.J.;Clark,B.A.J.;Hamish McNab,H.J.Chem.Soc.Perkin Trans.1,2001,4,424-428;
2.Srirupa,S.;Srivastava,B.B.L.Indian J.Hetero.Chem.,2005,15(1),51-54.
3.Chande,M.S.;Karnik,B.M.J.Indian Chem.Soc.1993,70,268.
4.Mohan,J.;Anianeylu,G.S.R.Pol.J.Chem.1987,61,547.
5.Sonasekhana,S.;Thakkar,R.K.;Shah,G.F.J.Indian Chem.Soc.1972,49,1057.
6.Samie,Z.K.;Ashmawi,M.I.;Fattah,B.Egypt J.Pharm.Sci.1988,29,251.
7.Kaplancikli,Z.A.;Zitouni,G.T.;Ozdemir,A.;Revial,G.Eur.J.Med.Chem.2008,43,155-159.
8.Tardito,S.;Bussolati,O.;Maffini,M.;Tegoni,M.;Giannetto,M.;Asta,V.D.;Gazzola,R.F.;Lanfranchi,M.;Pellinghelli,M.A.;Mucchino,C.;Mori,G.;Marchio,L.J.Med.Chem.2007,50,1916-1924.
9.George,T.;Tahitramani,R.;Dobholkar,A.Indian J.Chem.1969,7,959.
10.Shafei,A.K.;Gattas,A.B.;Sultan,A.;Kashef,H.S.;Vernin,G.Gazz.Chim.Ital.1982,112,345.
11.Garoufalias,S.S.P.;Tani,E.;Todoulou,O.;Valiraki,A.P.;Filippatos,E.J.Pharm.Pharmacol.1998,50,117-124.
12. Mathew, V.; Keshavayya, J.; Vaidya, V. P.; Giles, D. Eur. J. Med. Chem. 2007, 42, 823-840.
13. Metwally, K. A.; Yaseen, S. H.; M. Lashine, S. M. Eur. J. Med. Chem. 2007, 42, 152-160.
14. Mathewa, V.; Keshavayyab, J.; Vaidyab, V. P. Eur. J. Med. Chem. 2006, 41, 1048-1058.
15. Amir, M.; Kumar, H.; Sadique A. J. Bioorg. Med. Chem. Lett. 2007,17, 4504-4508.
16. Robins, R. K.; Revankar, G. R.; Clercq, E. D.; Walker, R. T.; Antiviral Drug Development, A Multidiscplinary Approach, Series A: Life Sciences, vol. 143, Plenium Press, New York, 1988, p. 11.
17. Elion, G. B. Science 1989, 244, 41.
18. Gudmundsson, K. S.; Freeman, G. A.; Drach, J. C.; Townsend, L. B. J. Med. Chem. 2000, 43 (12), 2473.
19. Khalil, S.A.M. Eur. J. Med. Chem. 2007, 42 ,1193-1199.
20. Tan. C. X.; Feng, R. F.; Peng, X. X. Chin. Chem. Lett. 2007,18 , 505-508.
21. Kritsanida, M.; Mouroutsou, A.; Marakos, P.; Pouli, N. Farmaco, 2002, 57, 253-257.
22. Swamy , S. N.; Priya, B. S.; Prabhuswamy, B.; Doreswamy, B.H.; Prasad, J. S. Eur. J. Med. Chem. 2006, 41, 531-538.
23. Dong, H. S.; Quan, B.; Zhu, D. W.; Li, W. D. J. Mole. Struc. 2002, 613,1-5.
2.White E.H.;Roswell D.F.Acc.Chem.Res.1970,3(2),54-62.
3.Licandro,E.;Perdicchia,D.Eur.J.Org.Chem.2004,665-675.
4.Hwang,S.W.;Chen,Y.Macromolecules 2002,35(14),5438-5443.
5.Zou,X.J.;Lai,L.H.;Jin,G.Y.J.Agric.Food Chem.2002,50(13),3757-3760.
6.PonticeUo,G.S.;Engelhardt,E.L.;Baldwin,J.J.J.Heterocyclic Chem.1980,17,425-427.
7.Gillet,J.P.Chem.Abstr.1992,117212.
8.刘素燕,惠新平,许鹏飞,张自义,高等学校化学学报,2000,21,1386.
9.Karnik,A.V.;Kamath,R.G.Indian J.Chem.Sect.B 1997,36B,803.
10.Dabiri,M.;Salehi,P.;Baghbanzadeha,M.;Bahramnejada,M.Tetrahedron Lett.2006,47,6983-6986.
11.Firoozi,F.;Javidnia,K.;Karnali,M.J.Heterocyclic Chem.1995,32,123.
12.Sun,X.W.;Hui,X.P.;Chu,C.H.;Zhang,Z.Y.Indian J.Chem.Sect.B 2001,40B,15.
13.Wang,Y.;Sauer,D.R.;Djuric,S.W.Tetrahedron Lett.2006,47,105-108.
14.Coppo,F.T.;Evans,K.A.;Graybill,T.L.;Burton,G.;Tetrahedron Lett.2004,45,3257-3260.
15.Hwang,J.Y.;Choi,H.S.;Lee,D.H.;Gong,Y.D.J.Comb.Chem.2005,7,816-819.
16.Kane,J.M.Synthesis 1987,912
17.Senthilvelan,A.;Thirumalai,D.;Ramakrishnan,V.T.Tetrahedron 2004,60,851.
18.Kane,J.M.;Ogden,A.M.L.Miller,J.A.J.Med.Chem.1994,37,125.
19.Klingele,M.H.;Brooker,S.Eur.J.Org.Chem.2004,3422.
20.Yeung,K.S.;Farkas,M.E.;Kadow,J.F.;Meanwell,N.F.Tetrahedron Lett.2005,46,3429-3432.
21.Carling,R.W.;Moore,K.W.J.Mad.Chem.2004,47,1807.
22.Stocks,M.J.,Cheshire,D.R.,Reynolds,R.Org.Lett.,2004,6,2969.
23.Hordiyenko,O.V.;Biitseva,A.V.;Kornilov,M.Y.;Brosse,N,;Hocquet,A.;Shishkin,O.V.;Zubatyuk,R.I.Eur.J.Org.Chem.2006,2833-2842
24.Ivachtchenko,A.;Kovalenko,S.;Tkachenko,O.V.;Parkhomenko,O.J.Comb.Chem.2004,6,573-583.
25.Okamura,T.;Kurogi,Y.;Hashimoto,K.;Nishikawaa,H.;Nagaob,Y.Bioorg.Med.Chem.Lett.2004,14,2443-2446.
26.Endo,Y.;Uchida,T.;Shudo,K.Tetrahedron Lett.1997,12,2113-2116.
27.Hameurlaine,A.;Abramov,M.A.;Dehaen,W.Tetrahedron Lett.2002,3,1015-1017.
28.Machkhoshvili,R.I.;Shchelokov,R.N.Russ.J.Coord.Chem.2000,26(10),677.
29.Hirsch-Kuchma,M.;Nicholson,T.;Davison,A.;Jones,A.G.J.Chem.Soc.,Dalton Trans.:Inorg.Chem.1997,18,3189.
30.Pickart,L.;Goodwin,W.H.;Murphy,T.B.;Johnson,D.K.J.Cell Biochem.Suppl.1982,6,482.
31.Sorenson,J.R.J.Chem.Ber.1984,20,1110.
32.Odunola,O.;Adeoye,I.;Woods,J.Synth.React.Inorg.Met.-Org.Chem.2002,32(4),801-817;
33.Licandro,E.;Maiorana,S.;Manzotti,R.;Papagni,A.;Perdicchia,D.;Pryce,M.;Tiripicchio,A.;Lanfranchi,M.Chem.Commun.1998,383-384.
34.Chande,M.S.;Kamik,B.M.J.Indian Chem.Soc.1993,70,268.
35.Hui,X.P.;Xu,P.F.;Wang,Q.;Zhang,Q.;Zhang Z.Y.Chin.J.Chem.2001,19,991.
36.Zhang,Z.Y.;Sun,X.W.Heterocycles 1998,48,561.
37.Zhang,Y.;Sun,X.W.;Hui,X.P.;Zhang,Z.Y.;Wang,Q.;Zhang,Q.Chin.Chem.2002,20,168.
38.曹玮,文丽荣,王啸,赵桂龙,李明,山东大学学报(自然科学版),2005,40117-120.
39.Srirupa,S.;Srivastava,B.B.Indian J.Heterocyclic Chem.,2005,15,51-54.
40. Cetin, A. Heterocycles, 2006, 68(9), 1901-1907
41. Wang, X. Chin. J. Org. Chem. 2005, 25(9), 1089-1093.
42. Dai, Z. F,; Zhang Z. Y.; Lanzhou Daxue Xuebao, Ziran Kexueban, 2002, 38(5), 51-57
43. Cartwright, D. D. J.; Clark, B. A. J.; Hamish McNab, H.J. Chem. Soc. Perkin Trans. 1,2001,4,424-428.
44. Invidiata, F. P.; Furno, G.; Lampronti, I.; Simoni, D. J. Heterocyclic Chem. 1997, 34(4), 1255-1258.
45. Goswami, B. N.; Kataky, J. C.; Baruah, J. N.J. Heterocyclic Chem. 1984, 21(4) , 225.
46. Sharma,R.S.; Babel, S. C. J. Indian Chem .Soc. 1982, 59, 877.
47. Gapta, A. S. K.; Misra, H. K. Indian J. Chem. Sect. B 1979,17b(2), 185.
48. Zhang, L. X.; Zhang, Z. Y. Chem. Chin. Univ. 1989,2, 147.
49. Fernandes, P. S.; Sonar, T. M. J. Indian Chem. Soc. 1988, Vol, LXV49.
50. Mohsen, A.; Omar, M. E.; Aboularafa, O. M.J. Heterocyclic Chem. 1986, 23, 1339.
51. Rajive, G.; Satya, P.; Avinash, K. G.; Kachroo, P. L. Indian J. Chem. 1994,33, 888.
52. Swamy, S. N.; Priya, B. S.; Prabhuswamy, B.; Doreswamy, B.H.; Prasad, J. S.; Rangappa, K.S. Eur. J. MedChem. 2006, 41, 531-538.
53. Xu, P. F.; Zhang, Z. H.; Hui, X. P.; Zheng, R. L. J. Chin. Chem. Soc. 2004, 51, 315.
54. Qiao, R. Z; Hui, X. P.; Xu, P. F ; Zhang, Z. Y.; Cheng, D. L. J. Chin. Chem. Soc. 2001, 19, 800.
55. Eisa, H. A.; Emam, A. A.; Moustafa, M. A.; Ashmawy, M. M. J. Chin. Chem. Soc. 1988, 35, 393.
56. Shukurov, S. S.; Kukaniev. M. A.; Bobgaribov, B. M.; Sabirov, S. S. Chem. Abstr. 1996,124, 289363.
57. Sun, X. W.; Hui, X. P.; Chu, C. H.; Zhang, Z. Y. Indian J. Chem. Sect. B 2000, 39B, 779.
58. Zhang, Z. Y.; Chen, X. Chin. J. Chem. 1992,10, 59.
59. Shukurov, S. S.; Kukaniev. M. A. Chem. Abstr. 1996,124, 558565.
60. Zhang, Z. Y.; Chen, X. Chin. J. Chem. 1992,10, 59.
61. Chande, M. S.; Karnik, B. M. J. Indian Chem. Soc. 1993, 70, 268.
62. Mohan, J. ; Anianeylu, G. S. R.Pol. J. Chem. 1987, 61, 547.
63. Sonasekhana, S.; Thakkar, R. K.; Shah, G. F. J. Indian Chem. Soc. 1972, 49, 1057.
64. Samie, Z. K. ; Ashmawi, M. I.; Fattah, B. Egypt J. Pharm. Sci. 1988,29, 251.
65. Sakata, M. ; Shirakawa, Y.; Kamata, N. ; Sakaguchi, Y.; Nishino, H.; Ouyang, J. ; Kurosawa, K. J. Heterocyclic Chem. 2000,37, 269.
66. Bhalerao, U. T. ; Muralikrishna, C. ; Rani, B. R. Tetrahedron 1994, 50, 4019.
67. Samie, Z. K.; Ashmawi, M. I.; Fattah, B. Egypt J. Pharm. Sci. 1988,29, 251.
68. Awad, I. M. A.; Rahman, A. E.; Bakite, E. A.J. Chem. Technol. Biotechnol. 1991, 51, 483.
69. Merrifield, R. B. J. Am. Chem. Soc. 1963, 85, 2149.
70. Recent reviews on SPOS. see: (a) Fruchtel, J. S.; Jung, G. Angew. Chem. Int. Ed. 1996, 35, 17. (b) Lorsbach, B. A.; Kurth, M. J. Chem. Rev. 1999, 99, 1549. (c) Guillier, F.; Orain, D.; Bradley, M.Chem. Rev. 2000,100, 2091. (d) Franzen, R. G. J. Comb. Chem. 2000, 2, 195. (e) Krchnak, V.; Holladay, M. W. Chem. Rev. 2002, 102, (f) Dolle, R. E.; Bourdonnec, B. E.; Morales, G. A.; Moriarty, K. J.; Salvino, J. M. J. Comb. Chem. 2006,8, 597-635.
71. (a) Dolle, R. E. J. Comb. Chem. 2004, 6, 623-679. (b)Kates, S. A.; Albericio, F. Macrcel Dekker, Inc, New York, 2000. (c)Burke, M. D.; Schreiber, S. L. Angew. Chem. Int. Ed. 1996, 43, 46-58.
72. Sahin, G.; Palaska, E.; Ekizoglu, M. Farmaco 2002, 57(2), 101-107.
73．赵金龙,硕士学位论文,浙江大学,杭州,2006．(Zhao, J. L., M. D. Thesis, Zhejiang University, Hangzhou, 2006)
1.Moro,S.;Braiuca,P.;Deflorian,F.;Ferrari,C.;Pastorin,G.;Cacciari,B.;Baraldi,P.B.J.Med.Chem.2005,48,152-162.
2.Baraldi,P.G.;Tabrizi,M.A.;Bovero,A.;Avitabile,B.;Preti,D.;Fruttarolo,F.;Romagnoli,R.;Varani,K.;Borea,P.A.Eur.J.Med.Chem.2003,38,367-382.
3.Baraldi,P.G.;Cacciari,B.;Romagnoli,R.;Spalluto,G.;Monopoli,A.;Ongini,E.;Borea,P.A.J.Med.Chem.2002,45,115-126.
4.Ongini,E.Drug Dev.Res.1997,42,63.
5.Neustadt,B.R.;Hao,J.;Lindo,N.;Greenlee,W.J.;Stamford,A.W.;Tulshian,D.;Ongini,E.;Hunter,J.;Monopoli,A.;Bertorelli,R.;Foster,C.Bioorg.Med.Chem.Lett.2007,17,1376-1380.
6.Baraldi,P.G.;Kashef,H.;Farghaly,A.R.;Vanelle,P.;Fruttarolo,F.Tetrahedron,2004,60,5093-5104.
7.Okamura,Y.;Kurogi,Y.;Hashimoto,K.;Nishikawa,H.;Nagao,Y.Bioorg.Med.Chem.Lett.2004,14,2443-2446.
8.赵金龙,硕士学位论文,浙江大学,杭州,2006.(Zhao,J.L,M D.Thesis,Zhejiang University,Hangzhou,2006)
9.Kane,J.M.;Baron,B.M.;Dudley,M.W.;Sorensen,S.M.;Staeger,M.A.; Miller, F. P. J. Med. Chem. 1990, 33, 2772.
10. Heers, J.; Back, J. J.; Cutsem, J. V. J. Med. Chem. 1984,27, 894.
11. Mullican, M. D.; Wilson, M. W.; Connor, D. T.; Kostlan, C. R.; Schrier, D. J.; Dyer, D. D. J. Med. Chem. 1993,36,1090.
12. Neslihan, D.; Reyhan, U.; Ahmet, D. Bioorg. Med. Chem. 2002,10, 3717.
13. Boschelli, D. H.; Connor, D. T.; Bornemeier, D. A.; Dyer, R. D.; Kennedy, J. A.; Okonkwo, G. C.; Schrier, D. J.; Wright, C. D.J. Med. Chem., 1993,36, 1802.
14. Romine, J. L.; Martin, S. W.; Gribkoff, V. K.; Boissard, C. G.; Dworetzky, S. I.; Natale, J.; Li, Y.; Gao, Q.; Meanwell, N. A.; Starrett, J. E.J. Med. Chem. 2002, 45, 2942.
15. Elipe, M. V. S.; Huskey S. W.; Zhu, B. J. Pharm. Biomed. Anal. 2003, 30, 1431 -1432
16. Xu, Y.; Mayhugh, D.; Saeed, A.; Wang, X.; Thompson, R. C.; Dominianni, S. J.; Kauffman, R. F.; Sing, J. ; Bean, J. S.; Bensch, W. R.; Barr, R. J.; Osborne, J.; Montrose- Rafizadeh, C.; Zink, R. W.; Yumibe, N. P.; Huang, N. D.; Rungta, D.; Maise, D. E.; Mantlo, N. B. J. Med. Chem. 2003, 46, 5121-5124.
17. Hamed, M. O.; Rabet, H.; Efrit, M. L. C. R. Chimie . 2007,10, 1147-1156.
18. Romine, J. L.; Martin, S. W.; Gribkoff, V. K.; Boissard, C. G.; Dworetzky, S.D.; Natale, J.; Li, Y.; Gao, Q.; Meanwell, N. A.; Starrett, J. E. J. Med. Chem. 2002, 45, 2942-2952
19. Bakulev, V. A.; Dehaen, W. "The Chemistry of 1,2,3-Thiadiazoles", in: The Chemistry of Heterocyclic Compounds (Ed.: Taylor, E. C.; Wipf, P.; Weissberger, A.), John Wiley & Sons, Inc., New York, 2004.
20. Katritzky, A. R.; Tymoshenko, D. O.; Nikonov G.N. J. Org. Chem. 2001, 66, 4045-4046.
21. Thomas, E. W.; Nishizawa, E. E.; Zimmermann, D. C.,Williams, D. J. J. Med. Chem. 1985, 28, 442.
22. Babu B. R.; Vaz ,A. D. N. Biochemistry 1997,36, 7209-7216.
23. Rabindranath , T.; Arup, G.; Jasbir, S.,; Edward, R. B., Thelma S. A., Bio.Med. Chem. Lett. 2007, 17, 1793-1798
24. Katritzky, A. R.; Tymoshenko, D. O.; Nikonov G.N. J. Org. Chem. 2001, 66, 4045-4046.
25. Latour, J. M.; Marchon, J. C.; Nakajima, M.J. Am. Chem. Soc. 1979 , 4, 101-114.
26. Katritzky, A. R.; Nikonov, G. N.; Moyano, E. L.; Novruz G. Akhmedov, N.G. ARKIVOC 2003, (vii), 121-138.
27. Rovira, C.; Veciana, J.; Santalb, N.; TarrBs, J.; Cirujeda, J.; Molins, E.;Llorca, J.; Espinosa, E. J. Org. Chem. 1994, 59, 3307-3313.
28.Thomas, E. W. Storr, R. C., Katritzky, A. R., Rees, C. W., Sriven, E. E V., Series Eds.; Pergamon: London, 1996; Vol. 4, p 289.
29.Thomas, E. W. Storr, R. C., Katritzky, A. R., Rees, C. W., Sriven, E. F. V., Series Eds.; Pergamon: London, 1996; Vol. 4, p 447.
30. Hinz, W.; Just, G. Synth. Commun. 1986, 917.
31. Hurd, C. D.; Mori, R. I. J. Am. Chem. Soc, 1955, 77, 5359-5364.
32. Chen, H.; Wang, W. H.; Xue, M.; Cao, R. Z.; Liu, L. Z. Heteroatom Chem. 2000, 11, 413-416.
33. Hu, Y; Baudart, S.; Porco, J. A.J. Org. Chem. 1999, 64, 1049-1051.
1.Cartwright,D.D.J.;Clark,B.A.J.;Hamish McNab,H.J.Chem.Soc.Perkin Trans.1,2001,4,424-428;
2.Srirupa,S.;Srivastava,B.B.L.Indian J.Hetero.Chem.,2005,15(1),51-54.
3.Chande,M.S.;Karnik,B.M.J.Indian Chem.Soc.1993,70,268.
4.Mohan,J.;Anianeylu,G.S.R.Pol.J.Chem.1987,61,547.
5.Sonasekhana,S.;Thakkar,R.K.;Shah,G.F.J.Indian Chem.Soc.1972,49,1057.
6.Samie,Z.K.;Ashmawi,M.I.;Fattah,B.Egypt J.Pharm.Sci.1988,29,251.
7.Kaplancikli,Z.A.;Zitouni,G.T.;Ozdemir,A.;Revial,G.Eur.J.Med.Chem.2008,43,155-159.
8.Tardito,S.;Bussolati,O.;Maffini,M.;Tegoni,M.;Giannetto,M.;Asta,V.D.;Gazzola,R.F.;Lanfranchi,M.;Pellinghelli,M.A.;Mucchino,C.;Mori,G.;Marchio,L.J.Med.Chem.2007,50,1916-1924.
9.George,T.;Tahitramani,R.;Dobholkar,A.Indian J.Chem.1969,7,959.
10.Shafei,A.K.;Gattas,A.B.;Sultan,A.;Kashef,H.S.;Vernin,G.Gazz.Chim.Ital.1982,112,345.
11.Garoufalias,S.S.P.;Tani,E.;Todoulou,O.;Valiraki,A.P.;Filippatos,E.J.Pharm.Pharmacol.1998,50,117-124.
12. Mathew, V.; Keshavayya, J.; Vaidya, V. P.; Giles, D. Eur. J. Med. Chem. 2007, 42, 823-840.
13. Metwally, K. A.; Yaseen, S. H.; M. Lashine, S. M. Eur. J. Med. Chem. 2007, 42, 152-160.
14. Mathewa, V.; Keshavayyab, J.; Vaidyab, V. P. Eur. J. Med. Chem. 2006, 41, 1048-1058.
15. Amir, M.; Kumar, H.; Sadique A. J. Bioorg. Med. Chem. Lett. 2007,17, 4504-4508.
16. Robins, R. K.; Revankar, G. R.; Clercq, E. D.; Walker, R. T.; Antiviral Drug Development, A Multidiscplinary Approach, Series A: Life Sciences, vol. 143, Plenium Press, New York, 1988, p. 11.
17. Elion, G. B. Science 1989, 244, 41.
18. Gudmundsson, K. S.; Freeman, G. A.; Drach, J. C.; Townsend, L. B. J. Med. Chem. 2000, 43 (12), 2473.
19. Khalil, S.A.M. Eur. J. Med. Chem. 2007, 42 ,1193-1199.
20. Tan. C. X.; Feng, R. F.; Peng, X. X. Chin. Chem. Lett. 2007,18 , 505-508.
21. Kritsanida, M.; Mouroutsou, A.; Marakos, P.; Pouli, N. Farmaco, 2002, 57, 253-257.
22. Swamy , S. N.; Priya, B. S.; Prabhuswamy, B.; Doreswamy, B.H.; Prasad, J. S. Eur. J. Med. Chem. 2006, 41, 531-538.
23. Dong, H. S.; Quan, B.; Zhu, D. W.; Li, W. D. J. Mole. Struc. 2002, 613,1-5.