SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF A NOVEL SERIES OF NONPEPTIDE ANGIOTENSIN-II RECEPTOR-BINDING INHIBITORS SPECIFIC FOR THE AT2 SUBTYPE
SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF A NOVEL SERIES OF NONPEPTIDE ANGIOTENSIN-II RECEPTOR-BINDING INHIBITORS SPECIFIC FOR THE AT2 SUBTYPE
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DOI：
10.1021/jm00115a014
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发表时间：
1991-11-01
影响因子：
7.3
通讯作者：
COHEN, DM
中科院分区：
文献类型：
--
作者：
BLANKLEY, CJ;HODGES, JC;COHEN, DM
报道了一类新的4，5，6，7-四氢-1H-咪唑并[4，5-c]吡啶-6-羧酸衍生物的构效关系，该衍生物取代了大鼠肾上腺制剂中血管紧张素II（Ang II）结合位点的特定子集中的I-125标记的血管紧张素II。该结合位点不是介导血管收缩或醛固酮释放的Ang II受体，而是其功能尚未完全阐明的结合位点。它已在许多组织中被鉴定，并与血管受体一样对Ang II及其肽类似物具有相似的亲和力。本文报道的非肽化合物在该结合位点处置换Ang II方面具有独特的特异性，并且在血管受体处拮抗Ang II或在测量血管效应的药理学测定中无活性。PD 123，319（79）是最有效的化合物之一，其IC 50为34 nM。这些化合物中的某些可能在Ang II受体亚型的定义和研究中具有效用。
Structure-activity relationships are reported for a novel class of 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid derivatives that displace I-125-labeled angiotensin II from a specific subset of angiotensin II (Ang II) binding sites in rat adrenal preparations. This binding site is not the Ang II receptor mediating vascular contraction or aldosterone release, but, rather, is one whose function has not yet been fully elucidated. It has been identified in a number of tissues and has a similar affinity for Ang II and its peptide analogues as does the vascular receptor. The non-peptide compounds reported here are uniquely specific in displacing Ang II at this binding site and are inactive in antagonizing Ang II at the vascular receptor or in pharmacological assays measuring vascular effects. PD 123,319 (79), one of the most potent compounds, has an IC50 of 34 nM. Certain of these compounds may have utility in the definition and study of Ang II receptor subtypes.