【药物名称】
化学结构式(Chemical Structure):
参考文献No.41537
标题:Fused azepinone cyclin dependent kinase inhibitors
作者:Gussio, R.; Zaharevitz, D.W.; Sausville, E.A.; Jalluri, R.K. (US Department of Health & Human Services)
来源:WO 9965910
合成路线图解说明:

5-Iodoanthranilic acid (I) was converted to ethyl ester (II) (1), which was subsequently reacted with ethoxysuccinyl chloride (III) to furnish the amide (IV). Dieckmann cyclization of (IV) using KH produced ketoester (V), and further dealkoxycarbonylation by heating in wet DMSO gave rise to benzazepinedione (VI). After formation of the corresponding hydrazone (VIII) with 4-(trifluoromethyl)phenylhydrazine (VII), Fisher indole synthesis yielded the paulone system (IX). The Heck reaction of (IX) with acrylonitrile in the presence of palladium catalyst gave adduct (X). The target saturated analogue was finally prepared by refluxing the acrylonitrile derivative (X) with Mg in MeOH.

参考文献No.576829
标题:2-Substituted paullones: CDK1/cyclin B-inhibiting property and in vitro antiproliferative activity
作者:Kunick, C.; Schultz, C.; Lemdke, T.; Zaharevitz, D.W.; Gussio, R.; Jalluri, R.K.; Sausville, E.A.; Leost, M.; Meijer, L.
来源:Bioorg Med Chem Lett 2000,10(6),567
合成路线图解说明:

5-Iodoanthranilic acid (I) was converted to ethyl ester (II) (1), which was subsequently reacted with ethoxysuccinyl chloride (III) to furnish the amide (IV). Dieckmann cyclization of (IV) using KH produced ketoester (V), and further dealkoxycarbonylation by heating in wet DMSO gave rise to benzazepinedione (VI). After formation of the corresponding hydrazone (VIII) with 4-(trifluoromethyl)phenylhydrazine (VII), Fisher indole synthesis yielded the paulone system (IX). The Heck reaction of (IX) with acrylonitrile in the presence of palladium catalyst gave adduct (X). The target saturated analogue was finally prepared by refluxing the acrylonitrile derivative (X) with Mg in MeOH.

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