GPR109a agonists. Part 1: 5-Alkyl and 5-aryl-pyrazole-tetrazoles as agonists of the human orphan G-protein coupled receptor GPR109a

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 8, 2009, Pages 2121-2124

  Imbriglio, Jason E ^a   Chang, Sookhee ^a   Liang, Rui ^a   Raghavan, Subharekha ^a   Schmidt, Darby ^a   Smenton, Abby ^a   Tria, Scott ^a   Schrader, Thomas O ^b   Jung, Jae Kyu ^b   Esser, Craig ^a   Taggart, Andrew K P ^a   Cheng, Kang ^a   Carballo Jane, Ester ^a   Gerard Waters, M ^a   Tata, James R ^a   Colletti, Steven L ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b ARENA PHARMACEUTICALS   (United States)

Author keywords

Atherosclerosis; GPR109a; Niacin

Indexed keywords

G PROTEIN COUPLED RECEPTOR; NICOTINIC ACID; PYRAZOLE DERIVATIVE; TETRAZOLE DERIVATIVE;

ANIMAL EXPERIMENT; ARTICLE; CHEMICAL REACTION; CONTROLLED STUDY; DRUG ACTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; MALE; MOUSE; NONHUMAN;

ANIMALS; HUMANS; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; NICOTINIC AGONISTS; PYRAZOLES; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, NICOTINIC; TETRAZOLES; VASODILATION;

EID: 63149143425     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.03.014     Document Type: Article

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15. The enantiomer of 8 d showed only modest affinity for the receptor, 7 μM (hNBA) and 5 μM (mNBA) respectively, illustrating a clear stereochemical preference for groups substituted in this C5 position.
16. A variety of functional groups including alkyl, naphthyl, trifluoromethoxy, trifluoromethyl, sulfonyl, and methoxy substituted ring systems were not tolerated in this region.
17. Measured using a Periscan PIMII Laser Doppler Perfusion Imager system.