Chemistry Division, Gedeon Richter Plc, Budapest 10, Hungary.
IP Department, Gedeon Richter Plc, Budapest, Hungary.
Expert Opin Ther Pat. 2023 Jan-Jun;33(5):385-395. doi: 10.1080/13543776.2023.2218546. Epub 2023 May 29.
Arginine-vasopressin hormone (AVP) is a key regulator in many essential physiological processes. The effect of AVP is mediated through three receptors within the body, these are the G protein-coupled vasopressin receptors, namely V1a, V1b (also called V3), and V2. Numerous studies investigated the role of these receptors in certain pathological conditions; therefore, stimulation or inhibition of these receptors may be a treatment option in these diseases.
In this manuscript, the authors summarize recent patent activity (2018-2022) associated with vasopressin receptor antagonists (selective V1a or V2, and dual-acting V1a/V2), focusing mostly on chemical structures, their modifications, and potential clinical applications. Patent search was carried out using SciFinder, Espacenet, Patentscope, Cortellis Competitive Intelligence, and Derwent Innovation databases.
In recent years, vasopressin receptor antagonists have been in the spotlight of drug discovery, especially V1a selective molecules. Publishing balovaptan as a possible treatment for autism spectrum disorder (ASD), greatly increased the interest in CNS-acting vasopressin antagonists. In addition, peripherally active selective V2 and dual-acting V1a/V2 antagonists have also been developed. Although clinical trials were unsuccessful in many cases, there is still potential in the research of vasopressin receptor antagonists as shown by several currently ongoing clinical trials.
精氨酸加压素激素（AVP）是许多基本生理过程的关键调节剂。AVP 的作用是通过体内的三种受体介导的，这些受体是 G 蛋白偶联的加压素受体，即 V1a、V1b（也称为 V3）和 V2。许多研究调查了这些受体在某些病理状况中的作用；因此，刺激或抑制这些受体可能是这些疾病的一种治疗选择。
在本文中，作者总结了与血管加压素受体拮抗剂（选择性 V1a 或 V2，以及双重作用 V1a/V2）相关的最近专利活动（2018-2022 年），主要集中在化学结构、修饰及其潜在的临床应用上。专利检索使用了 SciFinder、Espacenet、Patentscope、Cortellis 竞争情报和 Derwent Innovation 数据库。
近年来，血管加压素受体拮抗剂一直是药物发现的焦点，特别是 V1a 选择性分子。巴洛沙肽作为自闭症谱系障碍（ASD）的潜在治疗方法的发表，极大地增加了人们对中枢神经系统作用的血管加压素拮抗剂的兴趣。此外，还开发了外周活性选择性 V2 和双重作用 V1a/V2 拮抗剂。尽管在许多情况下临床试验都不成功，但目前正在进行的几项临床试验表明，血管加压素受体拮抗剂的研究仍有潜力。
