2. Academic Validation
  3. Pyrimidine-based antagonists of h-MCH-R1 derived from ATC0175: in vitro profiling and in vivo evaluation

Pyrimidine-based antagonists of h-MCH-R1 derived from ATC0175: in vitro profiling and in vivo evaluation

  • Bioorg Med Chem Lett. 2009 Nov 1;19(21):6166-71. doi: 10.1016/j.bmcl.2009.09.003.
Graeme Semple 1,  Thuy-Anh Tran,  Bryan Kramer,  Debbie Hsu,  Sangdon Han,  Juyi Choi,  Pureza Vallar,  Martin D Casper,  Ning Zou,  Erin K Hauser,  William Thomsen,  Kevin Whelan,  Dipanjan Sengupta,  Michael Morgan,  Yoshinori Sekiguchi,  Kosuke Kanuma,  Shigeyuki Chaki,  Andrew J Grottick
Affiliations

Affiliation

  • 1 Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, CA 92121, USA. gsemple@arenapharm.com
PMID: 19773162 DOI: 10.1016/j.bmcl.2009.09.003
Abstract

A series of pyrimidine analogues derived from ATC0175 were potent antagonists of human MCH-R1 in vitro. Significantly improved receptor selectivity was achieved with several analogues from this series, but no improvement in brain partitioning was noted. One example from this series was shown to inhibit food intake and decrease body weight in a chronic study. However no clear correlation between the pharmacodynamic effect and the pharmacokinetic data with respect to brain concentration was discernible leading us to conclude that the observed effect was most likely not due to interaction with the MCH-R1.

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