Abstract
A strategy for lead identification of new agonists of GPR109a, starting from known compounds shown to activate the receptor, is described. Early compound triage led to the formulation of a binding hypothesis and eventually to our focus on a series of pyrazole acid derivatives. Further elaboration of these compounds provided a series of 5,5-fused pyrazoles to be used as lead compounds for further optimization.
MeSH terms
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Acids, Heterocyclic / chemistry*
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Adipocytes / metabolism
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Animals
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Chemistry, Pharmaceutical / methods*
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Cyclic AMP / metabolism
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Drug Design
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Humans
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Kinetics
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Models, Chemical
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Niacin / chemistry
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Pyrazoles / chemistry
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Rats
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Receptors, G-Protein-Coupled / agonists*
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Receptors, G-Protein-Coupled / chemistry*
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Receptors, Nicotinic / chemistry*
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Spleen / metabolism
Substances
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Acids, Heterocyclic
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HCAR2 protein, human
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HCAR3 protein, human
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Pyrazoles
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Receptors, G-Protein-Coupled
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Receptors, Nicotinic
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Niacin
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Cyclic AMP