Analogues of acifran: agonists of the high and low affinity niacin receptors, GPR109a and GPR109b.
Recently identified GPCRs, GPR109a and GPR109b, the high and low affinity receptors for niacin, may represent good targets for the development of HDL elevating drugs for the treatment of atherosclerosis. Acifran, an agonist of both receptors, has been tested in human subjects, yet until recently very few analogs had been reported. We describe a series of acifran analogs prepared using newly developed synthetic pathways and evaluated as agonists for GPR109a and GPR109b, resulting in identification of compounds with improved activity at these receptors.
Jung
Jae-Kyu
JK
Department of Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, California 92121, USA.
Johnson
Benjamin R
BR
Duong
Tracy
T
Decaire
Marc
M
Uy
Jane
J
Gharbaoui
Tawfik
T
Boatman
P Douglas
PD
Sage
Carleton R
CR
Chen
Ruoping
R
Richman
Jeremy G
JG
Connolly
Daniel T
DT
Semple
Graeme
G
D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009525:Niacin / Q000378:metabolism* / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D005663:Furans; C530636:HCAR2 protein, human; C473653:HCAR3 protein, human; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D009525:Niacin; C036804:acifran; D000242:Cyclic AMP