Discovery of pyrazolyl propionyl cyclohexenamide derivatives as full agonists for the high affinity niacin receptor GPR109A.
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.
Ding
Fa-Xiang
FX
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. fa_xiang_ding@merck.com
Shen
Hong C
HC
Wilsie
Larrisa C
LC
Krsmanovic
Mihajlo L
ML
Taggart
Andrew K
AK
Ren
Ning
N
Cai
Tian-Quan
TQ
Wang
Junying
J
Tong
Xinchun
X
Holt
Tom G
TG
Chen
Qing
Q
Waters
M Gerard
MG
Hammond
Milton L
ML
Tata
James R
JR
Colletti
Steven L
SL
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
D000577:Amides; D053138:Cyclohexenes; C530636:HCAR2 protein, human; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; C052568:cyclohexene