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

…, J Bateson, GJ Hervieu, K Al-Barazanji, P Jeffrey…

Index: Witty, David R.; Bateson, John; Hervieu, Guillaume J.; Al-Barazanji, Kamal; Jeffrey, Phillip; Hamprecht, Dieter; Haynes, Andrea; Johnson, Christopher N.; Muir, Alison I.; O'Hanlon, Peter J.; Stemp, Geoffrey; Stevens, Alex J.; Thewlis, Kevin; Winborn, Kim Y. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 18 p. 4872 - 4878

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Citation Number: 18

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.