title: Discovery and characterization of a potent and selective antagonist of melanin-concentrating hormone receptor 2.
abstract: A series of spiropiperidine carbazoles were synthesized and evaluated as MCHR2 antagonists using a FLIPR assay. The pharmacokinetic properties of selected compounds have also been studied. This effort led to the discovery of potent and specific MCHR2 antagonists. Compound 38 demonstrated good pharmacokinetic properties across rat, beagle dog and rhesus monkey and had a favorable selectivity profile against a number of other receptors. These MCHR2 antagonists are considered appropriate tool compounds for study of the function of MCHR2 in vivo.
authors: Amgen Inc., 1120 Veterans Boulevard, ASF2-3, South San Francisco, CA 94080, USA. xiaoqic@amgen.com
authors: Xiaoqi
authors: X
authors: Chen
authors: Jeff
authors: J
authors: Mihalic
authors: Pingchen
authors: P
authors: Fan
authors: Lingming
authors: L
authors: Liang
authors: Michelle
authors: M
authors: Lindstrom
authors: Sylvia
authors: S
authors: Wong
authors: Qiuping
authors: Q
authors: Ye
authors: Ying
authors: Y
authors: Fu
authors: Juan
authors: J
authors: Jaen
authors: Jin-Long
authors: JL
authors: Chen
authors: Kang
authors: K
authors: Dai
authors: Leping
authors: L
authors: Li
mesh_terms: D000818:Animals; D016466:CHO Cells; D002227:Carbazoles / Q000737:chemistry*; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D006224:Cricetinae; D004285:Dogs; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008253:Macaca mulatta; D008956:Models, Chemical; D010880:Piperidines / Q000737:chemistry*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D002227:Carbazoles; C431280:MCHR2 protein, human; D010880:Piperidines; D043562:Receptors, G-Protein-Coupled; D011979:Receptors, Pituitary Hormone