Abstract
The design, synthesis and structure-activity relationship studies of a novel series of CRF-1 receptor antagonists, the 2-arylpyrimidines, are described. The effects of substitution on the aromatic ring and the pyrimidine core on CRF-1 receptor binding were investigated. A number of compounds with K(i) values below 10 nM and lipophilicity in a minimally acceptable range for a CNS drug (cLogP<5) were discovered.
MeSH terms
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Animals
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Binding Sites
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Chemistry, Pharmaceutical / instrumentation
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Chemistry, Pharmaceutical / methods*
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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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Molecular Conformation
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Molecular Structure
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry*
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Rats
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Rats, Sprague-Dawley
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Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
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Solubility
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Structure-Activity Relationship
Substances
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Pyrimidines
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Receptors, Corticotropin-Releasing Hormone