In silico identification of widely used and well-tolerated drugs as potential SARS-CoV-2 3C-like protease and viral RNA-dependent RNA polymerase inhibitors for direct use in clinical trials was written by Gul, Seref;Ozcan, Onur;Asar, Sinan;Okyar, Alper;Baris, Ibrahim;Kavakli, Ibrahim Halil. And the article was included in Journal of Biomolecular Structure and Dynamics in 2021.Name: 3-(2-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one This article mentions the following:
Despite strict measures taken by many countries, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be an issue of global concern. Currently, there are no clin. proven pharmacotherapies for coronavirus disease 2019, despite promising initial results obtained from drugs such as azithromycin and hydroxychloroquine. Therefore, the repurposing of clin. approved drugs for use against SARS-CoV-2 has become a viable strategy. Here, we searched for drugs that target SARS-CoV-2 3C-like protease (3CLpro) and viral RNA-dependent RNA polymerase (RdRp) by in silico screening of the U.S. Food and Drug Administration approved drug library. Well-tolerated and widely used drugs were selected for mol. dynamics (MD) simulations to evaluate drug-protein interactions and their persistence under physiol. conditions. Tetracycline, dihydroergotamine, ergotamine, dutasteride, nelfinavir, and paliperidone formed stable interactions with 3CLpro based on MD simulation results. Similar anal. with RdRp showed that eltrombopag, tipranavir, ergotamine, and conivaptan bound to the enzyme with high binding free energies. Docking results suggest that ergotamine, dihydroergotamine, bromocriptine, dutasteride, conivaptan, paliperidone, and tipranavir can bind to both enzymes with high affinity. As these drugs are well tolerated, cost-effective, and widely used, our study suggests that they could potentially to be used in clin. trials for the treatment of SARS-CoV-2-infected patients. In the experiment, the researchers used many compounds, for example, 3-(2-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (cas: 144598-75-4Name: 3-(2-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one).
3-(2-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (cas: 144598-75-4) belongs to isoxazole derivatives.Synthetically, isoxazoles serve as valuable precursors for the construction of diverse molecules, including many natural products. Isoxazole can be synthesised via a variety of methods. Examples include via the reaction of hydroxylamine with 1,3-diketones or derivatives of propiolic acid.Name: 3-(2-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one
Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem