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Medicinal Chemistry of AT2 Receptors

  • Chapter
Angiotensin Receptors

Abstract

Angiotensin II (ANG II) produces its physiological effects via interaction with its specific receptors that are distributed among a number of different tissues.1–4 The wide variety of receptor locations as well as their varying affinity for angiotensin peptidic fragments5,6 in the presence or absence of dithiothreitol (DTT) allowed some authors to speculate about ANG II receptor subtypes.7 Indeed, some authors referred to different affinity states,8–10 the ability of ligands to bind competitively versus noncompetitively,11–13 and to different signal transduction pathways14–17 to validate their case. However, it was not until the recent discovery of selective ligands that this receptor heterogeneity was clearly established.18–28 Since the AT1 receptor subtype29 mediates a variety of therapeutically important events, in particular, vascular smooth muscle contraction, there has been little effort directed toward the design and synthesis of AT2-specific ligands. However, as losartan (DuP 753)30–33 and numerous other AT1-selective antagonists34–33 progress through the clinical departments44–46 of pharmaceutical companies, one is left to consider the clinical consequence of AT2 receptor activation. Although at present there have been very few functional correlates identified with the AT2 receptor, it would seem reasonable to expect the role of the AT2 receptor to be revealed during the long-term administration of AT1 antagonists, as a consequence of elevated ANG II levels.

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan, 48105, USA

    Jeremy J. Edmunds & John C. Hodges

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  1. Jeremy J. Edmunds
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  2. John C. Hodges
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Editors and Affiliations

  1. National Institute of Mental Health National Institutes of Health, Bethesda, Maryland, USA

    Juan M. Saavedra

  2. The DuPont Merck Pharmaceutical Company, Wilmington, Delaware, USA

    Pieter B. M. W. M. Timmermans

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Edmunds, J.J., Hodges, J.C. (1994). Medicinal Chemistry of AT2 Receptors. In: Saavedra, J.M., Timmermans, P.B.M.W.M. (eds) Angiotensin Receptors. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2464-9_6

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