Discovery of potent and stable conformationally constrained analogues of the MCH R1 antagonist SB-568849.
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.
Witty
David R
DR
GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. david.witty@gsk.com
Bateson
John
J
Hervieu
Guillaume J
GJ
Al-Barazanji
Kamal
K
Jeffrey
Phillip
P
Hamprecht
Dieter
D
Haynes
Andrea
A
Johnson
Christopher N
CN
Muir
Alison I
AI
O'Hanlon
Peter J
PJ
Stemp
Geoffrey
G
Stevens
Alex J
AJ
Thewlis
Kevin
K
Winborn
Kim Y
KY
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
D000577:Amides; D000813:Anilides; D001713:Biphenyl Compounds; C103263:MCHR1 protein, human; D017481:Receptors, Somatostatin; C514078:SB-568849