Dmitri V. Kravchenko , Volodymyr M. Kysil , Sergey E. Tkachenko , Sergey Maliarchouk , Ilya M. Okun , Alexandre V. Ivachtchenko
{"title":"8-磺酰基-1,3-二氧基-2,3-二氢- 1h -吡咯啉[3,4-c]喹啉的合成及caspase-3抑制活性","authors":"Dmitri V. Kravchenko , Volodymyr M. Kysil , Sergey E. Tkachenko , Sergey Maliarchouk , Ilya M. Okun , Alexandre V. Ivachtchenko","doi":"10.1016/j.farmac.2005.08.001","DOIUrl":null,"url":null,"abstract":"<div><p><span>A convenient synthesis of novel 8-sulfonyl-1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines is described. As key steps to assemble the target molecular scaffold, our method features (a) Pfitzinger reaction of isatin-5-sulfonate </span><strong>1</strong> with methyl 3-oxo-3-phenylpropanoate, (b) formation of 1-(1H-pyrazol-4-yl)-1H-pyrrole-2,5-dione intermediate <strong>5</strong><span>, and (c) reaction of sulfinic acid </span><strong>9</strong><span> with acrylate<span><span> or methylacrylate leading to the corresponding </span>sulfonyl<span> propionates. Two compounds, ester </span></span></span><strong>11</strong> and morpholide <strong>13</strong>, have been identified as potent inhibitors of caspase-3 with IC<sub>50</sub> <!-->=<!--> <!-->6 nM. Our primary data suggest noncompetitive and reversible character of caspase-3 inhibition.</p></div>","PeriodicalId":77128,"journal":{"name":"Farmaco (Societa chimica italiana : 1989)","volume":"60 10","pages":"Pages 804-809"},"PeriodicalIF":0.0000,"publicationDate":"2005-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.farmac.2005.08.001","citationCount":"24","resultStr":"{\"title\":\"Synthesis and caspase-3 inhibitory activity of 8-sulfonyl-1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines\",\"authors\":\"Dmitri V. Kravchenko , Volodymyr M. Kysil , Sergey E. Tkachenko , Sergey Maliarchouk , Ilya M. Okun , Alexandre V. Ivachtchenko\",\"doi\":\"10.1016/j.farmac.2005.08.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>A convenient synthesis of novel 8-sulfonyl-1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines is described. As key steps to assemble the target molecular scaffold, our method features (a) Pfitzinger reaction of isatin-5-sulfonate </span><strong>1</strong> with methyl 3-oxo-3-phenylpropanoate, (b) formation of 1-(1H-pyrazol-4-yl)-1H-pyrrole-2,5-dione intermediate <strong>5</strong><span>, and (c) reaction of sulfinic acid </span><strong>9</strong><span> with acrylate<span><span> or methylacrylate leading to the corresponding </span>sulfonyl<span> propionates. Two compounds, ester </span></span></span><strong>11</strong> and morpholide <strong>13</strong>, have been identified as potent inhibitors of caspase-3 with IC<sub>50</sub> <!-->=<!--> <!-->6 nM. Our primary data suggest noncompetitive and reversible character of caspase-3 inhibition.</p></div>\",\"PeriodicalId\":77128,\"journal\":{\"name\":\"Farmaco (Societa chimica italiana : 1989)\",\"volume\":\"60 10\",\"pages\":\"Pages 804-809\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2005-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/j.farmac.2005.08.001\",\"citationCount\":\"24\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Farmaco (Societa chimica italiana : 1989)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0014827X05001722\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Farmaco (Societa chimica italiana : 1989)","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014827X05001722","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Synthesis and caspase-3 inhibitory activity of 8-sulfonyl-1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines
A convenient synthesis of novel 8-sulfonyl-1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines is described. As key steps to assemble the target molecular scaffold, our method features (a) Pfitzinger reaction of isatin-5-sulfonate 1 with methyl 3-oxo-3-phenylpropanoate, (b) formation of 1-(1H-pyrazol-4-yl)-1H-pyrrole-2,5-dione intermediate 5, and (c) reaction of sulfinic acid 9 with acrylate or methylacrylate leading to the corresponding sulfonyl propionates. Two compounds, ester 11 and morpholide 13, have been identified as potent inhibitors of caspase-3 with IC50 = 6 nM. Our primary data suggest noncompetitive and reversible character of caspase-3 inhibition.
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