开发含有三唑并氮杂卓支架的 V1a/V2 双拮抗剂

IF 6 2区医学 Q1 CHEMISTRY, MEDICINAL European Journal of Medicinal Chemistry Pub Date : 2025-02-05 DOI:10.1016/j.ejmech.2024.117069

Gábor Varró, Éva Bozó, Krisztina Vukics, Ferenc Baska, Gábor Szántó, Balázs Krámos, Katalin Domány-Kovács, Krisztina Szondiné Kordás, Mónika Vastag, Ildikó Magdó, Imre Bata

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引用次数: 0

摘要

开发 V1a/V2 双拮抗剂化合物是一项复杂而具有挑战性的任务。康尼伐他坦（Conivaptan）是迄今为止已知的唯一一种V1a/V2拮抗剂，已被批准用于治疗无水低钠血症。此前，我们曾报道过一种新型选择性 V1a 拮抗剂化合物 RGH-122。在此，我们介绍了几种很有前景的双拮抗剂化合物，它们是通过对 RGH-122 的尾部区域进行修饰而衍生出来的。这些修饰可使其在 V1a 和 V2 受体上产生极佳的结合亲和力。

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Development of dual V1a/V2 antagonists containing triazolobenzazepine scaffold

The development of a dual V1a/V2 antagonist compound is a complex and challenging task. Conivaptan is up to now the only known V1a/V2 antagonist which was approved for the treatment of euvolemic hyponatremia. Previously, we reported RGH-122, a novel selective V1a antagonist compound. Herein, we describe several promising dual antagonist compounds, which are derived from RGH-122 by using modifications in its tail region. These modifications can result in excellent binding affinity on both V1a and V2 receptors.

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来源期刊

European Journal of Medicinal Chemistry 化学-医药化学

CiteScore

11.70

自引率

9.00%

发文量

863

审稿时长

29 days

期刊介绍： The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers. A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.