Aryl[a]pyrrolo[3,4-c]carbazoles as selective cyclin D1-CDK4 inhibitors

✍ Scribed by Concha Sanchez-Martinez; Chuan Shih; Margaret M. Faul; Guoxin Zhu; Michael Paal; Carmen Somoza; Tiechao Li; Christine A. Kumrich; Leonard L. Winneroski; Zhou Xun; Harold B. Brooks; Bharvin K.R. Patel; Richard M. Schultz; Tammy B. DeHahn; Charles D. Spencer; Scott A. Watkins; Eileen Considine; Jack A. Dempsey; Catherine A. Ogg; Robert M. Campbell; Bryan A. Anderson; Jill Wagner

• Book ID: 104364091
• Publisher: Elsevier Science
• Year: 2003
• Tongue: English
• Weight: 195 KB
• Volume: 13
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/s0960-894x(03)00791-1

✦ Synopsis

The synthesis of new analogues of Arcyriaflavin A in which one indole ring is replaced by an aryl or heteroaryl ring is described. These new series of aryl[a]pyrrolo[3,4-c]carbazoles were evaluated as inhibitors of Cyclin D1-CDK4. A potent and selective D1-CDK4 inhibitor, 7a (D1-CDK4 IC 50 =45 nM), has been identified. The potency, selectivity profile against other kinases, and structure-activity relationship (SAR) trends of this class of compounds are discussed.