Cytotoxic α-bromoacrylic derivatives of distamycin analogues modified at the amidino moiety

被引：31

作者：

Cozzi, P

Beria, I

Caldarelli, M

Geroni, C

Mongelli, N

Pennella, G

机构：

[1] Pharmacia & Upjohn Inc, Discovery Res Oncol, Dept Chem, I-20014 Milan, Italy

[2] Pharmacia & Upjohn Inc, Discovery Res Oncol, Dept Pharmacol, I-20014 Milan, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 11期

关键词：

D O I：

10.1016/S0960-894X(00)00205-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The design, synthesis, in vitro and in vivo activities of novel alpha-bromoacrylic derivatives of distamycin A, modified at the amidino moiety by the replacement with basic or non-basic groups are reported. In spite of the relevance of these modifications of distamycin frame, the new derivatives are potent cytotoxics. The presence of the amidino moiety, is, therefore, not an absolute requirement for the activity. In particular due to a favorable myclotoxicity/cytotoxicity ratio, guanidino derivative PNU 166196 was selected for clinical development. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：1273 / 1276

页数：4

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