Title:
【発明の名称】CC-1065 及びズオカーマイシンのCBI 類縁体
Document Type and Number:
Japanese Patent JPH11513391
Kind Code:
A
Abstract:
Analogs of the antitumor antibiotics CC-1065 and the duocarmycins incorporate the 1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI) alkylation subunit. The CBI-based analogs have potent cytotoxic activity and are useful as efficacious antitumor compounds. A direct relationship between functional stability and in vitro cytotoxic potency is disclosed. The CBI-based analogs are easily synthesized and are 4x more stable and 4x more potent than the corresponding analogs containing the authentic CPI alkylation subunit of CC-1065 and comparable in potency to agents containing the authentic alkylation subunit of duocarmycin SA. Similarly, the CBI-based agents alkylate DNA with an unaltered sequence selectivity at an enhanced rate and with a greater efficiency than the corresponding CPI analog and were comparable to the corresponding analog incorporating the duocarmycin SA alkylation subunit. Systematic and extensive modifications and simplifications in the DNA binding subunits attached to CBI are also described.
Inventors:
Bogger Dale El
Application Number:
JP51452297A
Publication Date:
November 16, 1999
Filing Date:
October 03, 1996
Export Citation:
Assignee:
THE SCRIPPS RESEARCH INSTITUTE
International Classes:
A61K31/00; A61K31/34; A61K31/343; A61K31/40; A61K31/403; A61K31/404; A61P35/00; C07C281/02; C07D209/42; C07D209/60; C07D209/80; C07D209/96; C07D307/85; C07D333/68; C07D335/06; C07D405/12; C07D405/14; C07D409/12; C07D409/14; C07D487/04; C07D498/04; C07D519/00; (IPC1-7): C07D209/60; A61K31/00; A61K31/34; A61K31/40; C07C281/02; C07D209/80; C07D307/85; C07D333/68; C07D405/12; C07D405/14; C07D409/12; C07D409/14; C07D487/04
Attorney, Agent or Firm:
Minoru Nakamura (7 outside)