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ID: ALA1139297

Journal: Bioorg Med Chem Lett

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

Authors: Stevens KL, Alligood KJ, Alberti JG, Caferro TR, Chamberlain SD, Dickerson SH, Dickson HD, Emerson HK, Griffin RJ, Hubbard RD, Keith BR, Mullin RJ, Petrov KG, Gerding RM, Reno MJ, Rheault TR, Rusnak DW, Sammond DM, Smith SC, Uehling DE, Waterson AG, Wood ER.

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.

CiteXplore: 19028424

DOI: 10.1016/j.bmcl.2008.11.023