Abstract
6-Phenylnicotinamide (2) was previously identified as a potent TRPV1 antagonist with activity in an in vivo model of inflammatory pain. Optimization of this lead through modification of both the biaryl and heteroaryl components has resulted in the discovery of 6-(4-fluorophenyl)-2-methyl-N-(2-methylbenzothiazol-5-yl)nicotinamide (32; SB-782443) which possesses an excellent overall profile and has been progressed into pre-clinical development.
MeSH terms
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Administration, Oral
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Animals
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Benzothiazoles / chemical synthesis*
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Benzothiazoles / pharmacology
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Capsaicin / chemistry
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Cell Line
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Guinea Pigs
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Humans
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Inflammation
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Inhibitory Concentration 50
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Models, Chemical
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Niacinamide / analogs & derivatives*
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Niacinamide / chemical synthesis*
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Niacinamide / chemistry
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Niacinamide / pharmacology
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Rats
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TRPV Cation Channels / antagonists & inhibitors*
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TRPV Cation Channels / chemistry*
Substances
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6-(4-fluorophenyl)-2-methyl-N-(2-methylbenzothiazol-5-yl)nicotinamide
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Benzothiazoles
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TRPV Cation Channels
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TRPV1 protein, human
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Niacinamide
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Capsaicin