2. Academic Validation
  3. Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors

Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors

  • Bioorg Med Chem Lett. 2009 Jan 1;19(1):21-6. doi: 10.1016/j.bmcl.2008.11.023.
Kirk L Stevens 1,  Krystal J Alligood,  Jennifer G Badiang Alberti,  Thomas R Caferro,  Stanley D Chamberlain,  Scott H Dickerson,  Hamilton D Dickson,  Holly K Emerson,  Robert J Griffin,  Robert D Hubbard,  Barry R Keith,  Robert J Mullin,  Kimberly G Petrov,  Roseanne M Gerding,  Michael J Reno,  Tara R Rheault,  David W Rusnak,  Douglas M Sammond,  Stephon C Smith,  David E Uehling,  Alex G Waterson,  Edgar R Wood
Affiliations

Affiliation

  • 1 Department of Oncology Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. Kirk.L.Stevens@GSK.com
PMID: 19028424 DOI: 10.1016/j.bmcl.2008.11.023
Abstract

A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 Receptor Tyrosine Kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on Enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described.

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