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• W2952132083 abstract "The fifth paper in this series describes the culmination of our investigations into the development of a potent and selective ET(A) receptor antagonist for the treatment of diseases mediated by ET-1. Receptor site mapping of several ET(A) antagonists prepared previously identified a common cationic binding site which prompted synthesis of phenoxyphenylacetic acid derivative 13a, which showed good in vitro activity (IC(50) 59 nM, rat aortic ET(A)). Optimization of 13a led to the identification of 27b, which exhibited an IC(50) of 4 nM. Although this did not translate into the expected in vivo potency, a compound of comparable in vitro activity, 27a (RPR118031A), showed a far better pharmacokinetic profile and in vivo potency (75 micromol/kg) and was duly proposed and accepted as a development candidate." @default.
• W2952132083 created "2019-06-27" @default.
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• W2952132083 date "2000-02-11" @default.
• W2952132083 modified "2023-10-15" @default.
• W2952132083 title "Selective ET_AAntagonists. 5. Discovery and Structure−Activity Relationships of Phenoxyphenylacetic Acid Derivatives" @default.
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• W2952132083 doi "https://doi.org/10.1021/jm990378b" @default.
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