Yaqoob Sana, Khan Farooq-Ahmad, Tanveer Nimra, Ali Shujaat, Hameed Abdul, El-Seedi Hesham, Jiang Zi-Hua, Wang Yan
Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Guangxi Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, Guangxi, People's Republic of China.
Third World Center for Science and Technology, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Sindh, Pakistan.
Drug Des Devel Ther. 2025 May 20;19:4039-4091. doi: 10.2147/DDDT.S513461. eCollection 2025.
Pyridine carboxylic acid isomers - picolinic acid, nicotinic acid, and isonicotinic acid - have historically resulted in a plethora of drugs against tuberculosis, cancer, diabetes, Alzheimer's, angina, dementia, depression, allergy, respiratory acidosis, psoriasis, acne, hypertension, hyperlipidemia, HIV/AIDS (specifically HIV-1), among others. Despite the large number of therapeutic agents derived from these isomers, the research involving these scaffolds is still exceptionally active. The current surge in enzyme inhibitory activities by the compounds derived from them has further created space for the discovery of new drug candidates. This review focuses on the medicinal relevance of these isomers by analyzing structure-activity relationships (SARs) and highlighting emerging trends from patents filed over the last decade. Notably, pharmaceutical giants like Bayer, Bristol-Myers Squibb, Novartis, Curis, and Aurigene have developed enzyme inhibitors based on these scaffolds with nanomolar potency. The role of these isomers in the development of antiviral agents, including protease inhibitors, is also discussed. Overall, this review brings to the readers, a pragmatic opportunity to comprehend the recent literature, highlighting the scaffolds' importance in the design of new enzyme inhibitors. Furthermore, it discusses the structure-activity relationship of pyridine carboxylic acid-derived compounds and highlights the current patenting trends in medicinal chemistry.
吡啶羧酸异构体——吡啶甲酸、烟酸和异烟酸——长期以来催生了大量用于治疗结核病、癌症、糖尿病、阿尔茨海默病、心绞痛、痴呆、抑郁症、过敏、呼吸性酸中毒、银屑病、痤疮、高血压、高脂血症、艾滋病毒/艾滋病（特别是HIV-1）等疾病的药物。尽管从这些异构体衍生出了大量治疗药物，但涉及这些骨架的研究仍然异常活跃。目前，由它们衍生的化合物在酶抑制活性方面的激增，进一步为发现新的候选药物创造了空间。本综述通过分析构效关系（SARs）并突出过去十年提交的专利中的新趋势，重点关注这些异构体的医学相关性。值得注意的是，拜耳、百时美施贵宝、诺华、Curis和奥瑞金等制药巨头已经开发出了基于这些骨架、具有纳摩尔效力的酶抑制剂。还讨论了这些异构体在包括蛋白酶抑制剂在内的抗病毒药物开发中的作用。总体而言，本综述为读者提供了一个务实的机会来理解近期文献，突出了这些骨架在新型酶抑制剂设计中的重要性。此外，它还讨论了吡啶羧酸衍生化合物的构效关系，并突出了药物化学领域当前的专利趋势。
