title: Discovery of pyrazolyl propionyl cyclohexenamide derivatives as full agonists for the high affinity niacin receptor GPR109A.
abstract: A series of pyrazolyl propionyl cyclohexenamides were discovered as full agonists for the high affinity niacin receptor GPR109A. The structure-activity relationship (SAR) studies were aimed to improve activity on GPR109A, reduce Cytochrome P450 2C8 (CYP2C8) and Cytochrome P450 2C9 (CYP2C9) inhibition, reduce serum shift and improve pharmacokinetic (PK) profiles.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. fa_xiang_ding@merck.com
authors.forename: Fa-Xiang
authors.initials: FX
authors.lastname: Ding
authors.forename: Hong C
authors.initials: HC
authors.lastname: Shen
authors.forename: Larrisa C
authors.initials: LC
authors.lastname: Wilsie
authors.forename: Mihajlo L
authors.initials: ML
authors.lastname: Krsmanovic
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Taggart
authors.forename: Ning
authors.initials: N
authors.lastname: Ren
authors.forename: Tian-Quan
authors.initials: TQ
authors.lastname: Cai
authors.forename: Junying
authors.initials: J
authors.lastname: Wang
authors.forename: Xinchun
authors.initials: X
authors.lastname: Tong
authors.forename: Tom G
authors.initials: TG
authors.lastname: Holt
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.forename: M Gerard
authors.initials: MG
authors.lastname: Waters
authors.forename: Milton L
authors.initials: ML
authors.lastname: Hammond
authors.forename: James R
authors.initials: JR
authors.lastname: Tata
authors.forename: Steven L
authors.initials: SL
authors.lastname: Colletti
mesh_terms: D000577:Amides / Q000737:chemistry*; D000818:Animals; D053138:Cyclohexenes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D011978:Receptors, Nicotinic; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D053138:Cyclohexenes; C530636:HCAR2 protein, human; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; C052568:cyclohexene