2. Academic Validation
  3. Biaryl purine derivatives as potent antiproliferative agents: inhibitors of cyclin dependent kinases. Part I

Biaryl purine derivatives as potent antiproliferative agents: inhibitors of cyclin dependent kinases. Part I

  • Bioorg Med Chem Lett. 2009 Dec 1;19(23):6608-12. doi: 10.1016/j.bmcl.2009.10.025.
Michael P Trova 1,  Keith D Barnes,  Curt Barford,  Travis Benanti,  Mark Bielaska,  Lori Burry,  John M Lehman,  Christine Murphy,  Harold O'Grady,  Denise Peace,  Susan Salamone,  Jennifer Smith,  Patricia Snider,  Joseph Toporowski,  Steven Tregay,  Alison Wilson,  Michael Wyle,  Xiaozhang Zheng,  Thomas D Friedrich
Affiliations

Affiliation

  • 1 AMRI, Medicinal Chemistry Department, 26 Corporate Circle, Albany, NY 12212-5098, USA.
PMID: 19846305 DOI: 10.1016/j.bmcl.2009.10.025
Abstract

The introduction of an aryl ring onto the 4-position of the C-6 benzyl amino group of the CDK Inhibitor roscovitine (2), maintained the potent CDK inhibition demonstrated by roscovitine (2) as well as greatly improving the antiproliferative activity. A series of C-6 biarylmethylamino derivatives was prepared addressing modifications on the C-6 biaryl rings, N-9 and C-2 positions to provide compounds that displayed potent cytotoxic activity against tumor cell lines. In particular, derivative 21h demonstrated a >750-fold improvement in the growth inhibition of HeLa cells compared to roscovitine (2).

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