带有 2-pentyl-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-one 环的 1,3,4-Thiadiazole 和 1,2,4-triazole-5-thione 衍生物：合成、分子对接、脲酶抑制和晶体结构,Archiv der Pharmazie

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带有 2-pentyl-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-one 环的 1,3,4-Thiadiazole 和 1,2,4-triazole-5-thione 衍生物：合成、分子对接、脲酶抑制和晶体结构
Archiv der Pharmazie ( IF 4.3 ) Pub Date : 2022-10-31 , DOI: 10.1002/ardp.202200355
Ergün Gültekin ₁ , Olcay Bekircan ₂ , Yakup Kara ₂ , Halil İbrahim Güler ₃ , Mustafa Serkan Soylu ₄ , Sevgi Kolaylı ₂

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两个系列的 1,3,4-thiadiazole ( 40a–o ) 和 1,2,4-triazole-5-thione ( 41a–l ) 衍生物带有 2-pentyl-5-phenyl-1,2,4-triazole合成了-3-一环，然后以硫脲为标准药物研究了它们的脲酶抑制活性。在两组中，第一组 ( 40a–o ) 没有表现出良好的活性，而第二组 ( 41a–l ) 表现出极好的活性。第二系列化合物中的化合物41j (1091.24 ± 14.02 µM) 的活性低于硫脲，而其余 11 种化合物 ( 41a–i、k和l ) 的活性优于硫脲 (183.92 ± 13.14 µM)。在 11 种化合物中，41b(15.96 ± 2.28 µM) 在苯环上具有 3-F 基团显示出最高的抑制活性。41b是最活跃的化合物，尿素酶动力学研究确定它具有非竞争性抑制潜力。此外，还对来自刀豆的脲酶与 27 种新的杂环化合物和参考分子进行了计算机分析，以了解导致脲酶活性的必要相互作用。所有化合物的对接计算支持与受体的结合比参考分子更强，具有高抑制常数。此外，通过单晶X射线衍射分析对化合物40m进行了表征。X 射线分析表明化合物的结构为40m在单斜晶系 P21/c 空间群中结晶，晶胞参数为：a = 10.2155(9) Å, b = 22.1709(18) Å, c = 21.4858(17) Å, β = 99.677(8)°, V = 4797.0( 7) Å ³。还进行了 X 射线衍射分析，以深入了解化合物40m中弱分子间相互作用和 CH…X（卤素）相互作用对晶体堆积的影响。

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1,3,4-Thiadiazole and 1,2,4-triazole-5-thione derivatives bearing 2-pentyl-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-one ring: Synthesis, molecular docking, urease inhibition, and crystal structure

Two series of 1,3,4-thiadiazole (40a–o) and 1,2,4-triazole-5-thione (41a–l) derivatives bearing a 2-pentyl-5-phenyl-1,2,4-triazole-3-one ring were synthesized and then studied for their urease inhibitory activities using thiourea as a standard drug. Among the two groups, the first group (40a–o) did not show good activity while the second group (41a–l) showed excellent activity. Compound 41j (1091.24 ± 14.02 µM) of the second series of compounds showed lower activity than thiourea, while the remaining 11 compounds (41a–i, k, and l) showed better activity than thiourea (183.92 ± 13.14 µM). Among the 11 compounds, 41b (15.96 ± 2.28 µM) having the 3-F group on the phenyl ring showed the highest inhibitory activity. Urease kinetic studies of 41b, which is the most active compound, determined it to have an un-competitive inhibition potential. Moreover, in silico analysis against urease from jack bean with 27 new heterocyclic compounds and the reference molecule was carried out to see the necessary interactions responsible for urease activity. The docking calculations of all compounds supported stronger binding to the receptor than the reference molecule, with high inhibition constants. In addition, compound 40m was characterized by single-crystal X-ray diffraction analysis. X-ray analysis reveals that the structures of the compound 40m crystallize in the monoclinic P21/c space group with the cell parameters: a = 10.2155(9) Å, b = 22.1709(18) Å, c = 21.4858(17) Å, β = 99.677(8)°, V = 4797.0(7) Å³. X-ray diffraction analyses were also performed to gain insights into the role of weak intermolecular interactions and C-H…X (halogen) interactions in compound 40m that influence the crystal packing.

更新日期：2022-10-31

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