Mohamed A. M. Abdel Reheim, Gameel A. M. Elhagali, Khadija E. Saadon, Nadia M. H. Taha, N. A. Mahmoud, Mohamed. S. A. El-Gaby
{"title":"作为类蛋白酶抑制剂的未知氯化噻唑烷、噻吩和 2-亚氨基苯并吡喃衍生物的设计、合成、表征和对接研究","authors":"Mohamed A. M. Abdel Reheim, Gameel A. M. Elhagali, Khadija E. Saadon, Nadia M. H. Taha, N. A. Mahmoud, Mohamed. S. A. El-Gaby","doi":"10.1007/s13738-024-03056-0","DOIUrl":null,"url":null,"abstract":"<div><p>The present work details the synthesis of several intriguing nitrogenous heterocycles utilizing a cyano-<i>N</i>-aryl-acetamide-reagent, notably chlorinated thiazolidine, thiophene and 2-iminochromene derivatives. Thus, the precursor 2-cyano-<i>N</i>-(2,4-dichlorophenyl) acetamide <b>1</b> underwent the reaction with phenyl isothiocyanate in DMF/KOH to afford the intermediate salt <b>3,</b> which reacted in situ with several α-halogenated reagents <b>4a-c</b> like ethylchloroacetate,α-bromoethylpropionate and α-bromo ethyl butaneoate and afforded the corresponding 4-thiazolidinnone derivatives <b>(6a–c,</b> yield%; 67–85), thiophene derivatives (<b>11</b>;yield 80%<b>)</b> and (<b>15,</b> yield 77%) obtained from the reaction of <b>3</b> with α- chloroacetyl acetone <b>9</b> and ethyl 2-chloro-3-oxobutanoate <b>12</b>.Novel series of different 4-thiazolidinones<b>(16a–e; </b>yield%; 65–84<b>)</b> were obtained via condensation of <b>6a</b> with different aldehydes. Finally, the reaction of compound <b>1 </b>with different bifunctional reagents, such as salicylaldehyde derivatives and 2-hydroxynaphthaldehyde, in ethanol furnished the iminochromenes <b>(17a,b;</b> yield %77,80) and (<b>18;</b> yield 85%). In addition, molecular docking studies of the prepared molecules were carried out against papain-like protease (PLpro) to identify novel promising inhibitors of Coronavirus Disease COVID-19. The binding affinity of the best docked compounds <b>16c</b> and <b>16a</b> toward the target enzyme was − 9.6 and − 8.9 kcal/mole, respectively. In silico-docking-Studies indicate, that compounds <b>16c</b> and <b>16a</b> have the potential as antiviral against COVID-19.</p><h3>Graphical abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":676,"journal":{"name":"Journal of the Iranian Chemical Society","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design, synthesis, characterization, and docking studies of hiherto unkown chlorinated thiazolidine, thiophene, and 2-iminochromene derivatives as protein-like protease inhibitors\",\"authors\":\"Mohamed A. M. Abdel Reheim, Gameel A. M. Elhagali, Khadija E. Saadon, Nadia M. H. Taha, N. A. Mahmoud, Mohamed. S. A. El-Gaby\",\"doi\":\"10.1007/s13738-024-03056-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The present work details the synthesis of several intriguing nitrogenous heterocycles utilizing a cyano-<i>N</i>-aryl-acetamide-reagent, notably chlorinated thiazolidine, thiophene and 2-iminochromene derivatives. Thus, the precursor 2-cyano-<i>N</i>-(2,4-dichlorophenyl) acetamide <b>1</b> underwent the reaction with phenyl isothiocyanate in DMF/KOH to afford the intermediate salt <b>3,</b> which reacted in situ with several α-halogenated reagents <b>4a-c</b> like ethylchloroacetate,α-bromoethylpropionate and α-bromo ethyl butaneoate and afforded the corresponding 4-thiazolidinnone derivatives <b>(6a–c,</b> yield%; 67–85), thiophene derivatives (<b>11</b>;yield 80%<b>)</b> and (<b>15,</b> yield 77%) obtained from the reaction of <b>3</b> with α- chloroacetyl acetone <b>9</b> and ethyl 2-chloro-3-oxobutanoate <b>12</b>.Novel series of different 4-thiazolidinones<b>(16a–e; </b>yield%; 65–84<b>)</b> were obtained via condensation of <b>6a</b> with different aldehydes. Finally, the reaction of compound <b>1 </b>with different bifunctional reagents, such as salicylaldehyde derivatives and 2-hydroxynaphthaldehyde, in ethanol furnished the iminochromenes <b>(17a,b;</b> yield %77,80) and (<b>18;</b> yield 85%). In addition, molecular docking studies of the prepared molecules were carried out against papain-like protease (PLpro) to identify novel promising inhibitors of Coronavirus Disease COVID-19. The binding affinity of the best docked compounds <b>16c</b> and <b>16a</b> toward the target enzyme was − 9.6 and − 8.9 kcal/mole, respectively. 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Design, synthesis, characterization, and docking studies of hiherto unkown chlorinated thiazolidine, thiophene, and 2-iminochromene derivatives as protein-like protease inhibitors
The present work details the synthesis of several intriguing nitrogenous heterocycles utilizing a cyano-N-aryl-acetamide-reagent, notably chlorinated thiazolidine, thiophene and 2-iminochromene derivatives. Thus, the precursor 2-cyano-N-(2,4-dichlorophenyl) acetamide 1 underwent the reaction with phenyl isothiocyanate in DMF/KOH to afford the intermediate salt 3, which reacted in situ with several α-halogenated reagents 4a-c like ethylchloroacetate,α-bromoethylpropionate and α-bromo ethyl butaneoate and afforded the corresponding 4-thiazolidinnone derivatives (6a–c, yield%; 67–85), thiophene derivatives (11;yield 80%) and (15, yield 77%) obtained from the reaction of 3 with α- chloroacetyl acetone 9 and ethyl 2-chloro-3-oxobutanoate 12.Novel series of different 4-thiazolidinones(16a–e; yield%; 65–84) were obtained via condensation of 6a with different aldehydes. Finally, the reaction of compound 1 with different bifunctional reagents, such as salicylaldehyde derivatives and 2-hydroxynaphthaldehyde, in ethanol furnished the iminochromenes (17a,b; yield %77,80) and (18; yield 85%). In addition, molecular docking studies of the prepared molecules were carried out against papain-like protease (PLpro) to identify novel promising inhibitors of Coronavirus Disease COVID-19. The binding affinity of the best docked compounds 16c and 16a toward the target enzyme was − 9.6 and − 8.9 kcal/mole, respectively. In silico-docking-Studies indicate, that compounds 16c and 16a have the potential as antiviral against COVID-19.
期刊介绍:
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