Abstract
Bioisosteric replacement of piperazine with an aryl ring in lead VR1 antagonist 1 led to the biarylamide series. The development of B-ring SAR led to the conformationally constrained analog 70. The resulting aminoquinazoline 70 represents a novel VR1 antagonist with improved in vitro potency and oral bioavailability vs the analogous compounds from the lead series.
MeSH terms
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Administration, Oral
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Amides / chemical synthesis
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Amides / pharmacokinetics
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Amides / pharmacology*
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Analgesics, Non-Narcotic / chemical synthesis*
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Analgesics, Non-Narcotic / pharmacokinetics
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Animals
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Biological Availability
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Humans
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Molecular Conformation
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Pain / drug therapy
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Quinazolines / chemical synthesis
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Quinazolines / pharmacology
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Rats
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Solubility
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Structure-Activity Relationship
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TRPV Cation Channels / antagonists & inhibitors*
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Urea / analogs & derivatives
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Urea / chemical synthesis
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Urea / pharmacology
Substances
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Amides
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Analgesics, Non-Narcotic
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Quinazolines
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TRPV Cation Channels
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TRPV1 protein, human
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Urea