Dacinostat, NVP-LAQ-824, LAQ-824-药物合成数据库

【药物名称】Dacinostat, NVP-LAQ-824, LAQ-824

化学结构式(Chemical Structure):

参考文献No.	54629
标题:	Deacetylase inhibitors
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)
来源:	WO 0222577

合成路线图解说明: 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No.	662014
标题:	Discovery and SAR of NVP-LAQ824, a novel histone deacetylase inhibitor with in vitro and in vivo antitumor activity
作者:	Perez, L.B.; Remiszewski, S.; Sambucetti, L.; et al.
来源:	Proc Am Assoc Cancer Res 2002,43Abst 3671

合成路线图解说明: 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.