title: Discovery of potent and stable conformationally constrained analogues of the MCH R1 antagonist SB-568849.
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.
authors.affiliation: GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. david.witty@gsk.com
authors.forename: David R
authors.initials: DR
authors.lastname: Witty
authors.forename: John
authors.initials: J
authors.lastname: Bateson
authors.forename: Guillaume J
authors.initials: GJ
authors.lastname: Hervieu
authors.forename: Kamal
authors.initials: K
authors.lastname: Al-Barazanji
authors.forename: Phillip
authors.initials: P
authors.lastname: Jeffrey
authors.forename: Dieter
authors.initials: D
authors.lastname: Hamprecht
authors.forename: Andrea
authors.initials: A
authors.lastname: Haynes
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Johnson
authors.forename: Alison I
authors.initials: AI
authors.lastname: Muir
authors.forename: Peter J
authors.initials: PJ
authors.lastname: O'Hanlon
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Stemp
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Stevens
authors.forename: Kevin
authors.initials: K
authors.lastname: Thewlis
authors.forename: Kim Y
authors.initials: KY
authors.lastname: Winborn
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000813:Anilides / Q000737:chemistry; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000813:Anilides; D001713:Biphenyl Compounds; C103263:MCHR1 protein, human; D017481:Receptors, Somatostatin; C514078:SB-568849