Discovery of potent and stable conformationally constrained analogues of the MCH R1 antagonist SB-568849

  • Bioorg Med Chem Lett. 2006 Sep 15;16(18):4872-8. doi: 10.1016/j.bmcl.2006.06.061.
David R Witty  1 ,  John Bateson ,  Guillaume J Hervieu ,  Kamal Al-Barazanji ,  Phillip Jeffrey ,  Dieter Hamprecht ,  Andrea Haynes ,  Christopher N Johnson ,  Alison I Muir ,  Peter J O'Hanlon ,  Geoffrey Stemp ,  Alex J Stevens ,  Kevin Thewlis ,  Kim Y Winborn
Affiliations
  • 1. GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. [email protected]
PMID: 16839763 DOI: 10.1016/j.bmcl.2006.06.061
Abstract

A strategy of systematically targeting more rigid analogues of the known MCH R1 receptor antagonist, SB-568849, serendipitously uncovered a binding mode accessible to N-aryl-phthalimide ligands. Optimisation to improve the stability of this compound class led to the discovery of novel N-aryl-quinazolinones, benzotriazinones and thienopyrimidinones as selective ligands with good affinity for human melanin-concentrating hormone receptor 1.

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