title: Discovery of orally bioavailable and novel urea agonists of the high affinity niacin receptor GPR109A.
abstract: A urea class of high affinity niacin receptor agonists was discovered. Compound 1a displayed good PK, better in vivo efficacy in reducing FFA in mouse than niacin, and no vasodilation in a mouse model. Compound 1q demonstrated equal affinity to GPR109A as niacin.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. hong_shen@merck.com
authors.forename: Hong C
authors.initials: HC
authors.lastname: Shen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Szymonifka
authors.forename: Divya
authors.initials: D
authors.lastname: Kharbanda
authors.forename: Qiaolin
authors.initials: Q
authors.lastname: Deng
authors.forename: Ester
authors.initials: E
authors.lastname: Carballo-Jane
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Wu
authors.forename: Tsuei-Ju
authors.initials: TJ
authors.lastname: Wu
authors.forename: Kang
authors.initials: K
authors.lastname: Cheng
authors.forename: Ning
authors.initials: N
authors.lastname: Ren
authors.forename: Tian-Quan
authors.initials: TQ
authors.lastname: Cai
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Taggart
authors.forename: Junying
authors.initials: J
authors.lastname: Wang
authors.forename: Xinchun
authors.initials: X
authors.lastname: Tong
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: D000818:Animals; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D008297:Male; D051379:Mice; D023421:Models, Animal; D015394:Molecular Structure; D009525:Niacin / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D011978:Receptors, Nicotinic; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D014664:Vasodilation / Q000187:drug effects
chemical_list: C473652:Hcar2 protein, mouse; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D009525:Niacin; D014508:Urea