title: 4-arylphthalazin-1(2H)-one derivatives as potent antagonists of the melanin concentrating hormone receptor 1 (MCH-R1).
abstract: A novel series of 4-arylphthalazin-1(2H)-one linked to arylpiperidines were synthesized and evaluated as MCH-R1 antagonists. The results of an extensive SAR study probing the effects of substituents on the 4-arylphthalazin-1(2H)-one C-4 aryl group led to the identification of the 4-(3,4-difluorophenyl) derivative as a highly potent MCH-R1 inhibitor with an IC(50)=1nM. However, further investigations showed that this substance has unacceptable pharmacokinetic properties including a high clearance and volume of distribution.
authors.affiliation: Bio-organic Science Division, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-600, Republic of Korea.
authors.forename: Chae Jo
authors.initials: CJ
authors.lastname: Lim
authors.forename: Soo Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Lee
authors.forename: Kwang-Seok
authors.initials: KS
authors.lastname: Oh
authors.forename: Kyu Yang
authors.initials: KY
authors.lastname: Yi
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006706:Homeostasis; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D009765:Obesity / Q000188:drug therapy*; D010793:Phthalazines / Q000494:pharmacology*; D011485:Protein Binding; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D019440:Anti-Obesity Agents; D001562:Benzimidazoles; D006834:Hydrazines; D010793:Phthalazines; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor