Abstract
Starting from the high throughput screening hit (3), novel N-tetrahydroquinolinyl, N-quinolinyl and N-isoquinolinyl carboxamides have been identified as potent antagonists of the ion channel TRPV1. The N-quinolinylnicotinamide (46) showed excellent potency at human, guinea pig and rat TRPV1, a favourable in vitro DMPK profile and activity in an in vivo model of inflammatory pain.
MeSH terms
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Animals
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Benzamides / chemical synthesis
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Benzamides / chemistry*
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Benzamides / pharmacology*
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Capsaicin / pharmacology
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Guinea Pigs
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Humans
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Isoquinolines / chemical synthesis
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Isoquinolines / chemistry*
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Isoquinolines / pharmacology*
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Liver / drug effects
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Liver / metabolism
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Molecular Structure
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Quinolines / chemical synthesis
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Quinolines / chemistry*
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Quinolines / pharmacology*
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Rats
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Structure-Activity Relationship
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TRPV Cation Channels / antagonists & inhibitors*
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TRPV Cation Channels / metabolism
Substances
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Benzamides
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Isoquinolines
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Quinolines
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TRPV Cation Channels
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TRPV1 receptor
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Capsaicin