Pub Date : 2023-12-14DOI: 10.14805/jphchem.2023.art124
Deepak Shilkar, Sabina Yasmin
Thiazolidinediones (TZDs), a well-known target of peroxisome proliferated receptors (PPARγ), have been clinically used as antidiabetic agents. PPARs belong to the nuclear receptor superfamily and are important targets (PPARs) for drugs that treat various metabolic disorders such as diabetes. We present comparative research on the meta-para substitution of benzylidene derivatives of thiazolidine-2,4-diones to identify their potential as modulators of PPARγ. PPARs are key drug targets in treating a range of metabolic disorders. In our previous study, we described 4-hydroxy benzylidene derivatives of thiazolidine-2,4-diones that exhibited a reversed orientation in the active site of PPARγ. The established pharmacophore was also discussed concerning the reversed conformation of the TZD fitting. In current silico studies, a focus is placed on meta-para-substituted benzylidene derivatives to identify H-bonding interactions analogous to those observed in the acidic head of rosiglitazone. All designed compounds exhibited strong hydrogen bonding interactions and displayed superior interaction energies compared to their monohydroxy counterparts. The results of a predicted ADMET report indicated that all molecules exhibited favourable hERG I & II properties, suggesting excellent metabolic stability.
噻唑烷二酮类化合物（TZDs）是众所周知的过氧化物酶体增殖受体（PPARγ）靶点，已被临床用作抗糖尿病药物。PPARs 属于核受体超家族，是治疗糖尿病等各种代谢性疾病药物的重要靶点（PPARs）。我们介绍了对噻唑烷-2,4-二酮的亚苄基衍生物进行元对位取代的比较研究，以确定它们作为 PPARγ 调节剂的潜力。PPAR 是治疗一系列代谢紊乱的关键药物靶点。在我们之前的研究中，我们描述了噻唑烷-2,4-二酮的 4-羟基苯亚甲基衍生物，它们在 PPARγ 的活性位点中表现出反向取向。此外，还讨论了有关 TZD 配合物反向构象的既定药理机制。在目前的硅学研究中，重点放在了元副取代的苯亚甲基衍生物上，以确定类似于在罗格列酮酸性头中观察到的氢键相互作用。与单羟基化合物相比，所有设计化合物都表现出强烈的氢键相互作用，并显示出更高的相互作用能。ADMET 预测报告的结果表明，所有分子都具有良好的 hERG I 和 II 特性，这表明它们具有出色的代谢稳定性。
{"title":"Molecular Docking Studies of Novel Thiazolidinedionederivatives as PPARγ Modulators","authors":"Deepak Shilkar, Sabina Yasmin","doi":"10.14805/jphchem.2023.art124","DOIUrl":"https://doi.org/10.14805/jphchem.2023.art124","url":null,"abstract":"Thiazolidinediones (TZDs), a well-known target of peroxisome proliferated receptors (PPARγ), have been clinically used as antidiabetic agents. PPARs belong to the nuclear receptor superfamily and are important targets (PPARs) for drugs that treat various metabolic disorders such as diabetes. We present comparative research on the meta-para substitution of benzylidene derivatives of thiazolidine-2,4-diones to identify their potential as modulators of PPARγ. PPARs are key drug targets in treating a range of metabolic disorders. In our previous study, we described 4-hydroxy benzylidene derivatives of thiazolidine-2,4-diones that exhibited a reversed orientation in the active site of PPARγ. The established pharmacophore was also discussed concerning the reversed conformation of the TZD fitting. In current silico studies, a focus is placed on meta-para-substituted benzylidene derivatives to identify H-bonding interactions analogous to those observed in the acidic head of rosiglitazone. All designed compounds exhibited strong hydrogen bonding interactions and displayed superior interaction energies compared to their monohydroxy counterparts. The results of a predicted ADMET report indicated that all molecules exhibited favourable hERG I & II properties, suggesting excellent metabolic stability.","PeriodicalId":508712,"journal":{"name":"Journal of Pharmaceutical Chemistry","volume":"82 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139179510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-11DOI: 10.14805/jphchem.2023.art297
S. Murtuja, Venkatesan Jayaprakash, B. N. Sinha
A new oxazole derivative, ethyl 5-bromo-2-(4-methoxyphenyl) oxazole-4-carboxylate, was synthesized and characterized by IR spectroscopy, 13C NMR, Mass spectroscopy, and single-crystal X-ray diffraction analysis. The asymmetric unit of the title compound has two independent molecules (A and B) arranged in an inverted planar orientation, stabilized by intramolecular C-H…O and C-H…N hydrogen bonds and intermolecular C-H…O hydrogen bonds. The crystallographic parameter for the structure C13H12BrNO4 is M =326.15 g/mol, monoclinic, sp. gr. P21/n (no. 14), a = 14.828(2) Å, b = 7.1335(9) Å, c = 25.119(2) Å, β = 100.066(11) °, V = 2616.1(6) Å3, Z = 8. Hirschfeld surface analysis and two-dimensional fingerprint plots provided insight into the short intermolecular interactions, and it was found that H···H (34.4%) interactions contributed the most to the intermolecular interactions. In contrast, the contribution of C · · · C (2.5 %) remained the least among all the interactions.
{"title":"Synthesis, crystal structure, and Hirschfeld surface analysis of novel ethyl 5-bromo-2-(4-methoxyphenyl) oxazole-4-carboxylate","authors":"S. Murtuja, Venkatesan Jayaprakash, B. N. Sinha","doi":"10.14805/jphchem.2023.art297","DOIUrl":"https://doi.org/10.14805/jphchem.2023.art297","url":null,"abstract":"A new oxazole derivative, ethyl 5-bromo-2-(4-methoxyphenyl) oxazole-4-carboxylate, was synthesized and characterized by IR spectroscopy, 13C NMR, Mass spectroscopy, and single-crystal X-ray diffraction analysis. The asymmetric unit of the title compound has two independent molecules (A and B) arranged in an inverted planar orientation, stabilized by intramolecular C-H…O and C-H…N hydrogen bonds and intermolecular C-H…O hydrogen bonds. The crystallographic parameter for the structure C13H12BrNO4 is M =326.15 g/mol, monoclinic, sp. gr. P21/n (no. 14), a = 14.828(2) Å, b = 7.1335(9) Å, c = 25.119(2) Å, β = 100.066(11) °, V = 2616.1(6) Å3, Z = 8. Hirschfeld surface analysis and two-dimensional fingerprint plots provided insight into the short intermolecular interactions, and it was found that H···H (34.4%) interactions contributed the most to the intermolecular interactions. In contrast, the contribution of C · · · C (2.5 %) remained the least among all the interactions.","PeriodicalId":508712,"journal":{"name":"Journal of Pharmaceutical Chemistry","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139360438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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