Laboratory of Human Diseases and Immunotherapy, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan University, Chengdu, 610041, China.
Laboratory of Human Diseases and Immunotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Eur J Med Chem. 2024 Sep 5;275:116593. doi: 10.1016/j.ejmech.2024.116593. Epub 2024 Jun 15.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. A total of 28 new molecular entities (NMEs) were approved by the U.S. Food and Drug Administration (FDA) for the treatment of cardiovascular diseases from 2011 to 2023. Approximately 25 % of the medications were sanctioned for the management of diverse vascular disorders. The other major therapeutic areas of focus included antilipemic agents (15 %), blood pressure disease (11 %), heart failure, hyperkalemia, and cardiomyopathy (7-8% each). Among all the approved drugs, there are a total of 22 new chemical entities (NCEs), including inhibitors, agonists, polymers, and inorganic compounds. In addition to NCEs, 6 biological agents (BLAs), including monoclonal antibodies, small interfering RNAs (siRNAs), and antisense oligonucleotides, have also obtained approval for the treatment of cardiovascular diseases. From this perspective, approved NCEs are itemized and discussed based on their disease, targets, chemical classes, major drug metabolites, and biochemical and pharmacological properties. Systematic analysis has been conducted to examine the binding modes of these approved drugs with their targets using cocrystal structure information or docking studies to provide valuable insights for designing next-generation agents. Furthermore, the synthetic approaches employed in the creation of these drug molecules have been emphasized, aiming to inspire the development of novel, efficient, and applicable synthetic methodologies. Generally, the primary objective of this review is to provide a comprehensive examination of the clinical applications, pharmacology, binding modes, and synthetic methodologies employed in small-molecule drugs approved for treating CVD. This will facilitate the development of more potent and innovative therapeutics for effectively managing cardiovascular diseases.
心血管疾病 (CVD) 是全球发病率和死亡率的主要原因。2011 年至 2023 年，美国食品和药物管理局 (FDA) 批准了 28 种新的分子实体 (NME) 用于治疗心血管疾病。大约 25%的药物被批准用于治疗各种血管疾病。其他主要关注的治疗领域包括抗脂类药物 (15%)、血压疾病 (11%)、心力衰竭、高钾血症和心肌病 (各占 7-8%)。在所有批准的药物中，共有 22 种新的化学实体 (NCE)，包括抑制剂、激动剂、聚合物和无机化合物。除了 NCE 之外，还有 6 种生物制剂 (BLAs)，包括单克隆抗体、小干扰 RNA (siRNA) 和反义寡核苷酸，也已获得批准用于治疗心血管疾病。从这个角度来看，根据疾病、靶点、化学类别、主要药物代谢物以及生化和药理学特性，对批准的 NCE 进行了分项讨论。使用共晶结构信息或对接研究对这些已批准药物与它们的靶点的结合模式进行了系统分析，为设计下一代药物提供了有价值的见解。此外，还强调了这些药物分子的合成方法，旨在激发新型、高效和适用的合成方法的发展。总的来说，本综述的主要目的是全面检查用于治疗 CVD 的小分子药物的临床应用、药理学、结合模式和合成方法。这将有助于开发更有效和创新的疗法，有效治疗心血管疾病。
