Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, 136119, India.
Ch. Devi Lal College of Pharmacy, Jagadhri, 135003, India.
Antiinflamm Antiallergy Agents Med Chem. 2024;23(1):39-51. doi: 10.2174/0118715230275741231207115011.
Pyrazole is a well-known nucleus in the pharmacy field with a wide range of other activities in addition to anti-inflammatory and analgesic, i.e., anticonvulsant, antiviral, and anticancer activities. There are well-known marketed drugs having pyrazole moiety as celecoxib, and lonazolac as COX-II inhibitors.
We aim to synthesize better anti-inflammatory than existing ones. Thiophene is also known for its analgesic and anti-inflammatory action. Thus, the fusion of both gives better anti-inflammatory agents. In the present studies, derivatives from two series of pyrazole were prepared by reacting substituted chalcone (3a-3f) derivatives prepared from 2-acetyl thiophene. They substituted aromatic aldehydes with phenyl hydrazine to form (5a-5f) and with 2, 4-dinitro phenyl hydrazine giving compounds (6a-6f) separately.
Purified and characterized pyrazoles have been analyzed for analgesic and anti-inflammatory activities by using standard methods. Compounds 5e, 5f, and 6d were proved to be potent analgesics and series (5a-5f) was found to have anti-inflammatory action, which was further validated using docking and ADME studies.
The ADME profile of synthesized compounds was found to be satisfactory.
The synthesized compounds can serve as lead for further drug designing.
吡唑是药学领域中广为人知的核心结构，除了具有抗炎和镇痛作用外，还具有抗惊厥、抗病毒和抗癌等多种活性。有一些知名的市售药物，如塞来昔布和洛那唑，都含有吡唑部分作为 COX-II 抑制剂。
我们旨在合成比现有药物更具抗炎活性的药物。噻吩也因其镇痛和抗炎作用而闻名。因此，两者的融合可以产生更好的抗炎药物。在本研究中，通过将取代的查尔酮（3a-3f）衍生物与苯肼反应，从 2-乙酰噻吩制备而来，合成了两个系列的吡唑衍生物。与取代的芳醛反应，分别与苯肼（5a-5f）和 2,4-二硝基苯肼（6a-6f）形成化合物。
通过使用标准方法，对纯化和表征的吡唑进行了镇痛和抗炎活性分析。化合物 5e、5f 和 6d 被证明具有较强的镇痛作用，而 5a-5f 系列则表现出抗炎作用，进一步通过对接和 ADME 研究进行了验证。
合成化合物的 ADME 特征被发现是令人满意的。
合成的化合物可以作为进一步药物设计的先导化合物。
