含二氟甲基药物及二氟甲基化试剂研究进展
|
摘要
本文首次介绍了2011～2018年美国FDA批准上市的所有含二氟甲基的药物,并总结了它们的主要临床用途。以化合物的电性效应为基准对国内外文献报道的二氟甲基化试剂进行分类综述,其中较为常见的是亲核二氟甲基化试剂,主要包括TMS类、Ph XCF2H类、Br CF2PO(OEt)2、苯磺酰二氟甲基类和苯磺酰二氟乙酸金属盐类,而亲电二氟甲基化试剂的研究和应用相对较少,已报道的主要有二氟甲基自由基供体和二氟有机金属盐类。
This paper presentes all Difluoromethyl-containing drugs approved by FDA in the United States from 2011 to 2018 for the first time. And briefly introduces their clinical applications. The Difluoromethylation reagents reported domestic and foreign are reviewed and classified based on their electrical effect. Among them, the nucleophilic difluoromethylation reagents are the most common ones. They mainly include TMS, PhXCF2 H, BrCF2 PO(OEt)2, Phenylsulfonyl and Phenylsulfonyl Difluoroacetic acid metal salts. The researches on electrophilic Difluoromethylation reagents are relatively fewer. Difluoromethyl radical donors and Difluorometallic salts have been reported.
This paper presentes all Difluoromethyl-containing drugs approved by FDA in the United States from 2011 to 2018 for the first time. And briefly introduces their clinical applications. The Difluoromethylation reagents reported domestic and foreign are reviewed and classified based on their electrical effect. Among them, the nucleophilic difluoromethylation reagents are the most common ones. They mainly include TMS, PhXCF2 H, BrCF2 PO(OEt)2, Phenylsulfonyl and Phenylsulfonyl Difluoroacetic acid metal salts. The researches on electrophilic Difluoromethylation reagents are relatively fewer. Difluoromethyl radical donors and Difluorometallic salts have been reported.
引文
[1]刘栓栓,王晶,许斌,等.近5年美国FDA批准上市的含氟药物研究进展[J].药学进展,2016,40(10):783-794.
[2]陈玲,刘艳红,邹栩,等.2016年美国FDA上市新药回顾及重点治疗领域在研药物评述[J].中国新药杂志,2017,26(12):1357-1369.
[3]魏利军.2017年美国、欧洲和日本批准的新药总结与点评(Ⅰ)[J].药学进展,2018,42(1):71-80.
[4]孙友松.2018年5月美国、欧盟和日本新批准药物概述[J].药学进展,2018,42(6):478-480.
[5]廖斌,廖清江.2011年美国FDA批准上市的新药[J].药学进展,2012,36(3):138-142.
[6]谭初兵,时丽丽,王士伟,等.2012年美国FDA批准新药介绍和分析[J].现代药物与临床,2013,28(3):415-420.
[7]陈玲,赵天笑,邹栩,等.2014年美国FDA批准上市新药回顾及重点药物分析[J].中国新药杂志,2015,24(4):361-370.
[8]张建忠.2015年7月FDA批准新药概况[J].上海医药,2015,36(17):79-80.
[9]Sankarganesh K,Sayan K,Jotheeswari K,et al.Nucleophilic difluoromethylation of aromatic aldehydes using trimethyl(trifluoromethyl)silane(TMSCF3)[J].J Fluorine Chem,2018,208(1):10-14.
[10]Suryaprakash GK,Sankarganesh K,Sayan K,et al.Direct S-difluoromethylation of thiols using the RuppertPrakash reagent[J].J Fluorine Chem,2015,180(3):186-191.
[11]Chen DB,Ni CF,Zhao YC,et al.A Key Intermediate in Nucleophilic Difluoromethylation of Enolizable Ketones with Me3Si CF2H[J].Angew Chem Int Ed,2016,55(6):12 632-12 636.
[12]Michurin OM,Radchenko DS,Komarov IV.Direct nucleophilic difluoromethylation of enolizable ketones with CHF2TMS/HMPA[J].Tetrahedron,72(10):1351-1356.
[13]Suryaprakash GK,Hu JB,Wang Y,et al.Fluoride-induced nucleophilic(phenylthio)difluoromethylation of carbonyl compounds with[difluoro(phenylthio)methyl]trimethylsilane(TMS-CF2SPh)[J].J Fluorine Chem,2005,126(4):527-532.
[14]Hu MY,Wang F,Zhao YC,et al.Difluoro(phenylchalcogen)methylation of aldehydes,ketones,and imines with S-,Se-,and Te-containing reagents Ph XCF2H(X=S,Se,Te)[J].J Fluorine Chem,2012,135(1):45-58.
[15]Mao T,Zhao L,Huang Y,et al.N-Difluoromethylation of imidazoles and pyrazoles using Br CF2PO(OEt)2 under mild condition[J].Tetrahedron Lett,2018,59(28):2752-2754.
[16]Liu J,Ni CF,Wang F,et al.Stereoselective synthesis ofα-difluoromethyl-β-amino alcohols via nucleophilic difluoromethylation with Me3Si CF2SO2Ph[J].Tetrahedron Lett,2008,49(10):1605-1608.
[17]Zhu LG,Li Y,Zhao YC,et al.Nucleophilic(phenylsulfonyl)difluoromethylation of alkyl halides using PhSO2CF2Si Me3:preparation of gem-difluoroalkenes and trifluoromethyl compounds[J].Tetrahedron Lett,2010,51(47):6150-6152.
[18]Li Y,Hu JB.Fluoride ion-mediated nucleophilic fluoroalkylation of alkyl halides with Me3Si CF2SPh:Synthesis of Ph SCF2-and CF2H-containing compounds[J].J Fluorine Chem,2008,129(5):382-385.
[19]Shen X,Liu QH,Luo T,et al.Nucleophilic Difluoromethylation of Epoxides with Ph SO(NTBS)CF2H by a Preorganization Strategy[J].Chem,2014,20(22):6795-6800.
[20]Zhu YJ,Lei ZL,Huang DK,et al.Decarboxylative Difluoromethylation of Aldehydes with Ph SO2CF2COOK:A Facile and Efficient Access to Difluoromethylated Carbinols[J].Tetrahedron Lett,2018,59(33):3184-3187.
[21]Wang W,Hua MQ,Huang Y,et al.Difluoromethylation of 2-hydroxychalcones using sodium 2-chloro-2,2-difluoroacetate as difluoromethylating agent[J].Chem Res Chinese U,2015,31(3):362-366.
[22]Hua MQ,Wang W,Liu WH,et al.Solvent-controlled difluoromethylation of 2′-hydroxychalcones for divergent synthesis of 2′-difluoromethoxychalcones and 2,2-difluoro-3-styryl-2,3-dihydrobenzofuran-3-ols[J].J Fluorine Chem,2016,181(1):22-29.
[23]Kim YJ,Kim DY.Visible light photoredox-catalyzed difluoromethylation and ring expansion of 1-(1-arylvinyl)cyclobutanols[J].J Fluorine Chem,2018,211(2):119-123.
[24]Hua WQ,Xua XH,Feng LQ.Visible light induced hydrodifluoromethylation of alkenes derived from oxindoles with(difluoromethyl)triphenylphosphonium bromide[J].JFluorine Chem,2018,208(1):73-79.
[25]Lin QY,Ran Y,Xu XH,et al.Photoredox-catalyzed bromodifluoromethylation of alkenes with difluoromethyltriphenylphosphonium bromide[J].Org Lett,2016,18(25):2419-2422.
[26]Zhang Z,Tang XJ,Dolbier WR.Photoredox-Catalyzed Intramolecular Difluoromethylation of N-Benzylacrylamides Coupled with Dearomatizing Spirocyclization:Access to CF2H-Containding 2-Azaspiro[4,5]deca-6,9-diene-3,8-diones[J].Org Lett,2016,18(10):1048-1051.
[27]Noto N,Koike T,Akita M.Diastereoselective Synthesis of CF3-and CF2H-Substituted Spiroethers from Aryl-Fused Cycloalkenylalkanols by Photoredox Catalysis[J].J Org Chem,2016,81(1):7064-7071.
[28]荣健,顾玉诚,胡金波,等.可见光促进下氟烷基砜对芳基烯烃的自由基氟烷基化反应[J].化学学报,2017,75(1):105-109.
[29]Zhu M,Fu WJ,Wang ZQ,et al.Visible-light-mediated direct difluoromethylation of alkynoates:synthesis of 3-difluoromethylated coumarins[J].Org Biomol Chem,2017,15(1):9057-9060.
[2]陈玲,刘艳红,邹栩,等.2016年美国FDA上市新药回顾及重点治疗领域在研药物评述[J].中国新药杂志,2017,26(12):1357-1369.
[3]魏利军.2017年美国、欧洲和日本批准的新药总结与点评(Ⅰ)[J].药学进展,2018,42(1):71-80.
[4]孙友松.2018年5月美国、欧盟和日本新批准药物概述[J].药学进展,2018,42(6):478-480.
[5]廖斌,廖清江.2011年美国FDA批准上市的新药[J].药学进展,2012,36(3):138-142.
[6]谭初兵,时丽丽,王士伟,等.2012年美国FDA批准新药介绍和分析[J].现代药物与临床,2013,28(3):415-420.
[7]陈玲,赵天笑,邹栩,等.2014年美国FDA批准上市新药回顾及重点药物分析[J].中国新药杂志,2015,24(4):361-370.
[8]张建忠.2015年7月FDA批准新药概况[J].上海医药,2015,36(17):79-80.
[9]Sankarganesh K,Sayan K,Jotheeswari K,et al.Nucleophilic difluoromethylation of aromatic aldehydes using trimethyl(trifluoromethyl)silane(TMSCF3)[J].J Fluorine Chem,2018,208(1):10-14.
[10]Suryaprakash GK,Sankarganesh K,Sayan K,et al.Direct S-difluoromethylation of thiols using the RuppertPrakash reagent[J].J Fluorine Chem,2015,180(3):186-191.
[11]Chen DB,Ni CF,Zhao YC,et al.A Key Intermediate in Nucleophilic Difluoromethylation of Enolizable Ketones with Me3Si CF2H[J].Angew Chem Int Ed,2016,55(6):12 632-12 636.
[12]Michurin OM,Radchenko DS,Komarov IV.Direct nucleophilic difluoromethylation of enolizable ketones with CHF2TMS/HMPA[J].Tetrahedron,72(10):1351-1356.
[13]Suryaprakash GK,Hu JB,Wang Y,et al.Fluoride-induced nucleophilic(phenylthio)difluoromethylation of carbonyl compounds with[difluoro(phenylthio)methyl]trimethylsilane(TMS-CF2SPh)[J].J Fluorine Chem,2005,126(4):527-532.
[14]Hu MY,Wang F,Zhao YC,et al.Difluoro(phenylchalcogen)methylation of aldehydes,ketones,and imines with S-,Se-,and Te-containing reagents Ph XCF2H(X=S,Se,Te)[J].J Fluorine Chem,2012,135(1):45-58.
[15]Mao T,Zhao L,Huang Y,et al.N-Difluoromethylation of imidazoles and pyrazoles using Br CF2PO(OEt)2 under mild condition[J].Tetrahedron Lett,2018,59(28):2752-2754.
[16]Liu J,Ni CF,Wang F,et al.Stereoselective synthesis ofα-difluoromethyl-β-amino alcohols via nucleophilic difluoromethylation with Me3Si CF2SO2Ph[J].Tetrahedron Lett,2008,49(10):1605-1608.
[17]Zhu LG,Li Y,Zhao YC,et al.Nucleophilic(phenylsulfonyl)difluoromethylation of alkyl halides using PhSO2CF2Si Me3:preparation of gem-difluoroalkenes and trifluoromethyl compounds[J].Tetrahedron Lett,2010,51(47):6150-6152.
[18]Li Y,Hu JB.Fluoride ion-mediated nucleophilic fluoroalkylation of alkyl halides with Me3Si CF2SPh:Synthesis of Ph SCF2-and CF2H-containing compounds[J].J Fluorine Chem,2008,129(5):382-385.
[19]Shen X,Liu QH,Luo T,et al.Nucleophilic Difluoromethylation of Epoxides with Ph SO(NTBS)CF2H by a Preorganization Strategy[J].Chem,2014,20(22):6795-6800.
[20]Zhu YJ,Lei ZL,Huang DK,et al.Decarboxylative Difluoromethylation of Aldehydes with Ph SO2CF2COOK:A Facile and Efficient Access to Difluoromethylated Carbinols[J].Tetrahedron Lett,2018,59(33):3184-3187.
[21]Wang W,Hua MQ,Huang Y,et al.Difluoromethylation of 2-hydroxychalcones using sodium 2-chloro-2,2-difluoroacetate as difluoromethylating agent[J].Chem Res Chinese U,2015,31(3):362-366.
[22]Hua MQ,Wang W,Liu WH,et al.Solvent-controlled difluoromethylation of 2′-hydroxychalcones for divergent synthesis of 2′-difluoromethoxychalcones and 2,2-difluoro-3-styryl-2,3-dihydrobenzofuran-3-ols[J].J Fluorine Chem,2016,181(1):22-29.
[23]Kim YJ,Kim DY.Visible light photoredox-catalyzed difluoromethylation and ring expansion of 1-(1-arylvinyl)cyclobutanols[J].J Fluorine Chem,2018,211(2):119-123.
[24]Hua WQ,Xua XH,Feng LQ.Visible light induced hydrodifluoromethylation of alkenes derived from oxindoles with(difluoromethyl)triphenylphosphonium bromide[J].JFluorine Chem,2018,208(1):73-79.
[25]Lin QY,Ran Y,Xu XH,et al.Photoredox-catalyzed bromodifluoromethylation of alkenes with difluoromethyltriphenylphosphonium bromide[J].Org Lett,2016,18(25):2419-2422.
[26]Zhang Z,Tang XJ,Dolbier WR.Photoredox-Catalyzed Intramolecular Difluoromethylation of N-Benzylacrylamides Coupled with Dearomatizing Spirocyclization:Access to CF2H-Containding 2-Azaspiro[4,5]deca-6,9-diene-3,8-diones[J].Org Lett,2016,18(10):1048-1051.
[27]Noto N,Koike T,Akita M.Diastereoselective Synthesis of CF3-and CF2H-Substituted Spiroethers from Aryl-Fused Cycloalkenylalkanols by Photoredox Catalysis[J].J Org Chem,2016,81(1):7064-7071.
[28]荣健,顾玉诚,胡金波,等.可见光促进下氟烷基砜对芳基烯烃的自由基氟烷基化反应[J].化学学报,2017,75(1):105-109.
[29]Zhu M,Fu WJ,Wang ZQ,et al.Visible-light-mediated direct difluoromethylation of alkynoates:synthesis of 3-difluoromethylated coumarins[J].Org Biomol Chem,2017,15(1):9057-9060.