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• W2952181503 abstract "The pseudotetrapeptide FR-139317 is a potent and highly selective antagonist of the endothelin-A (ETA) receptor; however, its peptidic nature leads to poor oral absorption characteristics which make it an unlikely drug candidate. In an attempt to improve these properties, we have replaced a portion of the amide bond framework of FR-139317 with a heterocyclic surrogate. The resultant analogs are also ETA-selective antagonists, but show a structure−activity profile substantially different from that of the peptidic series, particularly with regard to the requirements for the side chain group that has been incorporated into the heterocycle. The nature of the heterocycle itself also has profound effects on the activity of the compounds. Both of these surprising results can be rationalized through examination of a 3D model of ET ligand−receptor binding that has previously been developed in our laboratories." @default.
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• W2952181503 date "1996-01-01" @default.
• W2952181503 modified "2023-09-26" @default.
• W2952181503 title "Azole Endothelin Antagonists. 1. A Receptor Model Explains an Unusual Structure−Activity Profile" @default.
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• W2952181503 doi "https://doi.org/10.1021/jm950591h" @default.
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