2. Academic Validation
  3. Synthesis and pharmacological evaluation of aminopyrimidine series of 5-HT1A partial agonists

Synthesis and pharmacological evaluation of aminopyrimidine series of 5-HT1A partial agonists

  • Bioorg Med Chem Lett. 2009 Feb 15;19(4):1159-63. doi: 10.1016/j.bmcl.2008.12.087.
Amy B Dounay 1,  Nancy S Barta,  Jack A Bikker,  Susan A Borosky,  Brian M Campbell,  Terry Crawford,  Lynne Denny,  Lori M Evans,  David L Gray,  Pil Lee,  Edward A Lenoir,  Wenjian Xu
Affiliations

Affiliation

  • 1 Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, United States. Amy.Dounay@pfizer.com
PMID: 19147349 DOI: 10.1016/j.bmcl.2008.12.087
Abstract

Aminopyrimidine 2 (4-(1-(2-(1H-indol-3-yl)ethyl)piperidin-3-yl)-N-cyclopropylpyrimidin-2-amine) emerged from a high throughput screen as a novel 5-HT(1A) agonist. This compound showed moderate potency for 5-HT(1A) in binding and functional assays, as well as moderate metabolic stability. Implementation of a strategy for improving metabolic stability by lowering the lipophilicity (cLogD) led to identification of methyl ether 31 (4-(1-(2-(1H-indol-3-yl)ethyl)piperidin-3-yl)-N-(2-methoxyethyl)pyrimidin-2-amine) as a substantially improved compound within the series.

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