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Derivation of a 3D pharmacophore model for the angiotensin-II site one receptor

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Summary

A systematic search has been used to derive a hypothesis for the receptor-bound conformation of A-II antagonists at the AT1 receptor. The validity of the pharmacophore hypothesis has been tested using CoMFA, which included 50 diverse A-II antagonists, spanning four orders of magnitude in activity. The resulting cross-validated R2 of 0.64 (conventional R2 of 0.76) is indicative of a good predictive model of activity, and has been used to estimate potency for a variety of non-peptidyl antagonists. The structural model for the non-peptide has been compared with respect to the natural substrate, A-II, by generating peptide to non-peptide overlays.

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  1. Molecular Systems Department, Merck Research Laboratories, P.O. Box 2000, 07065, Rahway, NJ, U.S.A.

    Kristine Prendergast, Kym Adams, Robert B. Nachbar & Dennis J. Underwood

  2. Department of Exploratory Chemistry, Merck Research Laboratories, P.O. Box 2000, 07065, Rahway, NJ, U.S.A.

    William J. Greenlee & Arthur A. Patchett

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  1. Kristine Prendergast
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Prendergast, K., Adams, K., Greenlee, W.J. et al. Derivation of a 3D pharmacophore model for the angiotensin-II site one receptor. J Computer-Aided Mol Des 8, 491–512 (1994). https://doi.org/10.1007/BF00123662

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