Dacinostat, NVP-LAQ-824, LAQ-824
达诺司他Chemical Name: 3-[4-[N-(2-Hydroxyethyl)-N-[2-(1H-indol-3-yl)ethyl]aminomethyl]phenyl]-2(E)-propenohydroxamic acid
CAS No. 404951-53-7
项目整合开发状态: Phase I
项目研究机构: Novartis (Originator)
合成路线:The esterification of 4-formylcinnamic acid (I) with methanol and HCl gives the methyl ester (II),which can be obtained by Heck coupling of 4-bromobenzaldehyde (III) with methyl acrylate (IV).The reductocondensation of (II) with tryptamine (V) by means of NaBH(OAc)3 in dichloroethane yields the secondary amine (VI),which is alkylated with 2-(tert-butyldimethylsilyloxy)ethyl bromide (VII) by means of DIEA in DMSO to afford the tertiary amine (VIII).The reaction of the methyl ester group of (VIII) with KOH and hydroxylamine in methanol provides the silylated hydroxamic acid (IX),which is finally deprotected with TFA in water.
📌 参考资料/链接：
参考文献标题:Deacetylase inhibitors
文献作者:Bair,K.W.; Versace,R.W.; Green,M.A.; Remiszewski,S.W.; Perez,L.B.; Sambucetti,L.; Sharma,S.K.(Novartis AG; Novartis-Erfindungen VmbH)
参考来源:WO 0222577
📄 详细内容
合成路线:The esterification of 4-formylcinnamic acid (I) with methanol and HCl gives the methyl ester (II),which can be obtained by Heck coupling of 4-bromobenzaldehyde (III) with methyl acrylate (IV).The reductocondensation of (II) with tryptamine (V) by means of NaBH(OAc)3 in dichloroethane yields the secondary amine (VI),which is alkylated with 2-(tert-butyldimethylsilyloxy)ethyl bromide (VII) by means of DIEA in DMSO to afford the tertiary amine (VIII).The reaction of the methyl ester group of (VIII) with KOH and hydroxylamine in methanol provides the silylated hydroxamic acid (IX),which is finally deprotected with TFA in water.
参考文献标题:Discovery and SAR of NVP-LAQ824,a novel histone deacetylase inhibitor with in vitro and in vivo antitumor activity
文献作者:Perez,L.B.; Remiszewski,S.; Sambucetti,L.; et al.
参考来源:Proc Am Assoc Cancer Res 2002,43Abst 3671
产品链接: CAS No. 404951-53-7››