ABT-770
N-[2-(4,4-二甲基-2,5-二氧硅咪唑酮-1-基)-1(S)-[4'-(三氟甲氧基)双苯基-4-酰氧甲基]乙基]-N-羟基甲酰胺Chemical Name: N-[2-(4,4-Dimethyl-2,5-dioxoimidazolidin-1-yl)-1(S)-[4'-(trifluoromethoxy)biphenyl-4-yloxymethyl]ethyl]-N-hydroxyformamide
CAS No. 220614-50-6, 220614-32-4 (undefined isomer)
项目整合开发状态: Preclinical
项目研究机构: Abbott (Originator)
合成路线:Suzuki coupling between 4-methoxyphenylboronic acid (I) and 1-bromo-4-(trifluoromethoxy)benzene (II) gave the biphenyl derivative (III).Methyl ether cleavage in (III) by means of BBr3 provided the biphenyl alcohol (IV),which was condensed with (S)-benzyl glycidyl ether (V) under basic conditions,yielding the chiral glycerol diether (VI).Mitsunobu coupling of alcohol (VI) with the di-Boc-protected hydroxylamine (VII) using DEAD/PPh3 afforded carbamate (VIII).Subsequent catalytic hydrogenolysis of the benzyl ether of (VIII) gave alcohol (IX).Condensation of this alcohol (IX) with 5,5-dimethylhydantoin (X) under Mitsunobu conditions,followed by acidic cleavage of the Boc protecting groups,furnished the hydroxylamine derivative (XI).This was finally N-formylated by treatment with formic acetic anhydride.
📌 参考资料/链接：
参考文献标题:Reverse hydroxamate inhibitors of matrix metalloproteinases
文献作者:Dellaria,J.F.Jr.; Gong,J.; Steinman,D.H.; Michaelides,M.R.; Giesler,J.; Davidsen,S.K.; Curtin,M.L.; Florjancic,A.S.; Xu,L.; Guo,Y.; Holms,J.H.; Wada,C.K.; Heyman,H.R.(Abbott Laboratories Inc.)
参考来源:JP 2001523272; WO 9906361
📄 详细内容
合成路线:Suzuki coupling between 4-methoxyphenylboronic acid (I) and 1-bromo-4-(trifluoromethoxy)benzene (II) gave the biphenyl derivative (III).Methyl ether cleavage in (III) by means of BBr3 provided the biphenyl alcohol (IV),which was condensed with (S)-benzyl glycidyl ether (V) under basic conditions,yielding the chiral glycerol diether (VI).Mitsunobu coupling of alcohol (VI) with the di-Boc-protected hydroxylamine (VII) using DEAD/PPh3 afforded carbamate (VIII).Subsequent catalytic hydrogenolysis of the benzyl ether of (VIII) gave alcohol (IX).Condensation of this alcohol (IX) with 5,5-dimethylhydantoin (X) under Mitsunobu conditions,followed by acidic cleavage of the Boc protecting groups,furnished the hydroxylamine derivative (XI).This was finally N-formylated by treatment with formic acetic anhydride.
参考文献标题:Discovery and characterization of the potent,selective and orally bioavailable MMP inhibitor ABT-770
文献作者:Curtin,M.L.; Florjancic,A.S.; Heyman,H.R.; Michaelides,M.R.; Garland,R.B.; Holms,J.H.; Steinman,D.H.; Dellaria,J.F.; Gong,J.; Wada,C.K.; Guo,Y.; Elmore,I.B.; Tapang,P.; Albert,D.H.; Magoc,T.J.; Marcotte,P.A.; Bouska,J.J.; et al.
参考来源:Bioorg Med Chem Lett 2001,11(12),1557
产品链接: CAS No. 220614-50-6››