Synthesis, SAR and docking studies of substituted aryl phenylthiazolyl phenylcarboxamide as potential protein tyrosine phosphatase 1B ( PTP 1B) inhibitors
| Autor: | Kanika Varshney, Arvind K. Srivastava, Sudha Jain, Akansha Mishra, Amit K Gupta, Mridula Saxena, Rohit Srivastava, Anil Kumar Saxena, Arun Rawat |
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| Rok vydání: | 2019 |
| Předmět: |
Blood Glucose
Male Stereochemistry Mice Obese 01 natural sciences Biochemistry Diabetes Mellitus Experimental Mice Structure-Activity Relationship chemistry.chemical_compound In vivo Catalytic Domain Drug Discovery Animals Humans Hypoglycemic Agents Enzyme Inhibitors Hypolipidemic Agents Protein Tyrosine Phosphatase Non-Receptor Type 1 Pharmacology Sulfonyl chemistry.chemical_classification Binding Sites 010405 organic chemistry Drug discovery Aryl Organic Chemistry Glucose Tolerance Test Amides Protein Tyrosine Phosphatase 1B 0104 chemical sciences Mice Inbred C57BL Molecular Docking Simulation 010404 medicinal & biomolecular chemistry chemistry Docking (molecular) Drug Design Molecular Medicine Selectivity Lead compound hormones hormone substitutes and hormone antagonists |
| Zdroj: | Chemical Biology & Drug Design. 94:1378-1389 |
| ISSN: | 1747-0285 1747-0277 |
| DOI: | 10.1111/cbdd.13515 |
| Popis: | In our continued effort to discover novel PTP1B inhibitor with improved in vivo activity, we attempted to optimize our previously discovered lead compound by replacing the sulfonyl group with benzoyl group to yield compound II. Additional structural modifications were performed on compound II to yield a series of 24 aryl phenylthiazolyl phenylcarboxamides as potential PTP1B inhibitors. Of the 24 tested, 6 compounds showed good PTP1B inhibitory activity while compound 38 as the most promising one. The plausible PTP1B-binding site interaction of compound 38 showed favourable binding similar to known PTP1B binders and suggests its selectivity towards PTP1B. Compound 38 also showed promising antihyperglycaemic, antidyslipidaemic and insulin resistant reversal activities in vivo in STZ model and db/db mice model. Altogether, the compound 38 presents an excellent candidate for future PTP1B targeted drug discovery. |
| Databáze: | OpenAIRE |
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