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. Epub 2006 Jul 12.

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.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Anilides / chemistry
  • Biphenyl Compounds / chemical synthesis
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacology*
  • Humans
  • Molecular Structure
  • Receptors, Somatostatin / antagonists & inhibitors*
  • Receptors, Somatostatin / metabolism
  • Structure-Activity Relationship

Substances

  • Amides
  • Anilides
  • Biphenyl Compounds
  • MCHR1 protein, human
  • Receptors, Somatostatin
  • SB-568849