HPLC of Formula: C9H10O3. Authors Wadhwa, P; Jain, P; Jadhav, HR in BENTHAM SCIENCE PUBL LTD published article about in [Wadhwa, Pankaj; Jain, Priti; Jadhav, Hemant R.] Birla Inst Technol & Sci, Dept Pharm, Pilani 333031, Rajasthan, India; [Wadhwa, Pankaj] Lovely Profess Univ, Lovely Sch Pharmaceut Sci, Phagwara 144401, Punjab, India; [Jain, Priti] RC Patel Inst Pharmaceut Educ & Res, Shirpur, Dhule, India in 2021.0, Cited 18.0. The Name is 2,5-Dimethoxybenzaldehyde. Through research, I have a further understanding and discovery of 93-02-7
Aim: To design, synthesis and in vitro evaluation of 4-oxo-6-substituted phenyl-2-thioxo 1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives as HIV integrase strand transfer inhibitors. Background: Human immunodeficiency virus-1 (HIV-1), a member of retroviridae family, is the primary causative agent of acquired immunodeficiency syndrome (AIDS). Three enzymes viz: integrase (IN), reverse transcriptase (RT) and protease play important role in its replication cycle. HIV-1 integrase is responsible for the incorporation of viral DNA into human chromosomal DNA by catalyzing two independent reactions, 3′-processing (3′-P) and strand transfer (ST), which are observed as the point of no-return in HIV infection. Objective: To develop inhibitors against HIV integrase strand transfer step. Methods: Our previous results indicated that tetrahydro pyrimidine-5-carboxamide derivatives are potent HIV-1 IN inhibitors (unpublished results from our laboratory). Taking clue from above studies and our own experience, we hypothesized 4-oxo-6-substituted phenyl-2-thioxo 1,2,3,4-tetrahydropyrimidine-5-carbonitrile analogues (14a to 14n) as inhibitors of HIV-1 Integrase strand transfer. Prototype compound 14 can be viewed as hybrid structure having characteristics of dihydropyrimidine derivatives 10-12 and tyrphostin 13. Results: A total of fourteen derivatives of 4-oxo-6-substituted phenyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile (14a-14n) were synthesized and evaluated using HIV-1 Integrase Assay Kit (Xpressbio Life Science Products, USA). The percentage inhibition of all compounds was investigated at 10 mu M concentration and IC50 value of few highly active compounds was studied. The obtained results were validated by in silico molecular docking study using Glide (maestro version 9.3, Schrodinger suite) in extra precision (XP) mode. Conclusion: Fourteen 4-oxo-6-substituted phenyl-2-thioxo 1,2,3,4-tetrahydropyrimidine-5-carbonitrile analogues were synthesized and evaluated for HIV-1 IN inhibitory activity. Three compounds 14a, 14e, and 14h exhibited significant percentage inhibition of HIV-1 IN. There was good in vitro – in silico correlation. However, none of the derivative was active against HIV-1 and HIV-2 below their cytotoxic concentration. It needs to be seen whether these compounds can be explored further for their anti-HIV or cytotoxic potential.
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