Heterobiaryl purine derivatives as potent antiproliferative agents: inhibitors of cyclin dependent kinases. Part II

  • Bioorg Med Chem Lett. 2009 Dec 1;19(23):6613-7. doi: 10.1016/j.bmcl.2009.10.011.
Michael P Trova  1 ,  Keith D Barnes ,  Luis Alicea ,  Travis Benanti ,  Mark Bielaska ,  Joseph Bilotta ,  Brian Bliss ,  Thuy Nguyen Duong ,  Simon Haydar ,  R Jason Herr ,  Yu Hui ,  Matthew Johnson ,  John M Lehman ,  Denise Peace ,  Matthew Rainka ,  Patricia Snider ,  Susan Salamone ,  Steven Tregay ,  Xiaozhang Zheng ,  Thomas D Friedrich
Affiliations
  • 1. AMRI, Medicinal Chemistry Department, 26 Corporate Circle, Albany, NY 12212-5098, USA.
PMID: 19854650 DOI: 10.1016/j.bmcl.2009.10.011
Abstract

C-6 Biarylmethylamino purine derivatives of roscovitine (1) inhibit cyclin dependent Kinases and demonstrate potent antiproliferative activity. Replacement of the aryl rings of the C-6 biarylmethylamino group with heterobiaryl rings has provided compounds with significantly improved activity. In particular, derivatives 18 g and 9 c demonstrated 1000-fold and 1250-fold improvements, respectively, in the growth inhibition of HeLa cells compared to roscovitine (1).