抗肿瘤及抗病毒药物的研究——Ⅵ.消旋β-邻苯二甲酰亚氨-α-正丁酮醛衍生物的合成

本文报告消旋β-邻苯二甲酰亚氨-α-正丁酮醛(Ⅵ),其双缩氨硫脲(Ⅶ)(Ⅴ6133),双缩氨脲(Ⅷ),其与对氨基苯甲酸缩合物(Ⅸ)以及2-α-邻苯二甲酰亚氨乙基-1,4-喹(口恶)啉(Ⅹ)的合成,以寻找抗肿瘤及抗病毒药物。生理活性筛选及临床试验表明Ⅴ6133是一种新型结构的抗砂眼病毒药。

STUDIES ON ANTITUMOR AND ANTIVIRAL COMPOUNDS Ⅵ.SYNTHESIS OF dl-β-PHTHALIMIDO-α-n-BUTYRALDEHYDE DERIVATIVES

It has been shown that the alkoxyl moiety of β-ethoxy-α-keto-n-butyraldehyde bis-thiosemicarbazone (C6323) can be varied without much effect on its antitumor activity. The synthesis of β-phthalimido-α-keto-n-butyraldehyde in which phthalimido group replaced the ethoxyl group of β-ethoxy-α-keto-n-butyraldehyde (Kethoxal)is described. Derivatives of the title compound, bis-thiosemicarbazone Ⅶ (Ⅴ6133), his-semi carbazone Ⅷ, condensation product. Ⅸ with p-aminobenzoic acid, and 2-α-phthalimidoethyl-1,4-quinoxazoline Ⅹ were prepared. Compound Ⅶ (Ⅴ6133) exhibited marked antitrachomatous (Yu-2) activity at a minimum inhibition concentration of 0.5μg/ml in vitro and was also highly effective against Walker 256 carcinoma in rats. Clinical trials indicated that the compound Ⅶ (Ⅴ6133) is a useful drug in the treatment of infectious trachoma in human.