麦角生物碱。作为潜在抗癌剂的麦角灵亚硝基脲衍生物的合成。

Ergot alkaloids. Synthesis of nitrosourea derivatives of ergolines as potential anticancer agents.

作者信息

Crider A M, Lu C K, Floss H G, Cassady J M, Clemens J A

出版信息

J Med Chem. 1979 Jan;22(1):32-5. doi: 10.1021/jm00187a008.

Abstract

Nitrosourea derivatives of ergolines have been synthesized for the purpose of obtaining agents with both prolactin-and tumor-inhibitory activity. Two derivatives of 8-amino-6-methylergoline (3), 8-[3-(2-chloroethyl)-3-nitrosoureido]-1-nitroso-6-methylergoline (5c) and 8-[3-2-chloroethyl)-3-nitrosoureido]-6-methylergoline (5a), have been prepared. In addition, nitroso (7) and chloroethylcarbamyl (8) derivatives of elymoclavine (6) are reported. Compounds 5a and 5c have activity against L1210 leukemia in mice but only moderate prolactin-inhibiting activity. The chloroethylcarbamyl derivative 8 of elymoclavine is a potent prolacting inhibitor.

摘要

为了获得具有催乳素抑制和肿瘤抑制活性的药物，已合成了麦角灵的亚硝基脲衍生物。制备了8-氨基-6-甲基麦角灵（3）的两种衍生物，8-[3-(2-氯乙基)-3-亚硝基脲基]-1-亚硝基-6-甲基麦角灵（5c）和8-[3-(2-氯乙基)-3-亚硝基脲基]-6-甲基麦角灵（5a）。此外，还报道了麦角隐亭（6）的亚硝基（7）和氯乙基氨基甲酰基（8）衍生物。化合物5a和5c对小鼠L1210白血病有活性，但催乳素抑制活性中等。麦角隐亭的氯乙基氨基甲酰基衍生物8是一种有效的催乳素抑制剂。