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

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

Affiliation

  • 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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