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

  • Bioorg Med Chem Lett. 2003 Nov 3;13(21):3835-9. doi: 10.1016/s0960-894x(03)00791-1.
Concha Sanchez-Martinez  1 ,  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
Affiliations
  • 1. DCR&T, Lilly Spain S.A., Avda de la Industria 30, 28108 Alcobendas, Madrid, Spain. [email protected]
PMID: 14552791 DOI: 10.1016/s0960-894x(03)00791-1
Abstract

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.

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