Department of Applied Chemistry, Z.H. College of Engineering & Technology, Aligarh Muslim University, Aligarh 202002, India.
Division of Organic Synthesis, Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
Steroids. 2022 Dec;188:109120. doi: 10.1016/j.steroids.2022.109120. Epub 2022 Oct 5.
The present work reports simple and effective protocol for preparing 6α-nitro-5α-cholestano[7α,5-cd] pyrazolines (4-7) by the reaction of 7α-bromo-6-nitrocholest-5-enes (1-3) with hydrazine hydrate under reflux [the substrate (2) gave products (5) and (6) and the later on acetylation with ACO/Py gave (7)]. In the case of reaction of 3β-hydroxy analogue (3) with hydrazine, however, 6α-nitro-5α-cholestano [3α,5-cd] pyrazoline (8) and 6α-nitro-3β, 5-oxido-5β-cholestane (9) were obtained. The probable mechanism of the formation of pyrazolines has also been outlined. In the current pandemic coronavirus disease 2019 scenario, the in-silico study was performed with reactants (1-3), their products (4-9) against SARS-CoV-2 omicron protease (PDB ID:7T9L) for knowing significant interactions between them. Docking results give information that both reactants and products have binding energies ranges from -5.7 to 7.7 kcal/mol and strong interactions with various hydrophilic and hydrophobic amino acids such as ASP, PRO, PHE, SER and LEU which are significant residues playing important role in SARS-CoV-2 Omicron main protease (Mpro).
本工作报道了一种简单有效的方法，通过 7α-溴代-6-硝基胆甾-5-烯（1-3）与水合肼在回流下反应，制备 6α-硝基-5α-胆甾烷[7α,5-cd]吡唑啉（4-7）[底物（2）得到产物（5）和（6），后者用 ACO/Py 乙酰化得到（7）]。然而，在 3β-羟基类似物（3）与水合肼的反应中，得到了 6α-硝基-5α-胆甾烷[3α,5-cd]吡唑啉（8）和 6α-硝基-3β,5-氧化-5β-胆甾烷（9）。还概述了吡唑啉形成的可能机制。在当前的 2019 年冠状病毒病大流行背景下，对反应物（1-3）及其产物（4-9）进行了针对 SARS-CoV-2 奥密克戎蛋白酶（PDB ID：7T9L）的计算机研究，以了解它们之间的重要相互作用。对接结果表明，反应物和产物都具有-5.7 至 7.7 kcal/mol 的结合能范围，并与各种亲水和疏水氨基酸（如 ASP、PRO、PHE、SER 和 LEU）具有强烈的相互作用，这些氨基酸是在 SARS-CoV-2 奥密克戎主蛋白酶（Mpro）中发挥重要作用的重要残基。
