Discovery of cyclic sulfonamide derivatives as potent inhibitors of SARS-CoV-2
[Display omitted] Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) continues to spread worldwide, with 25 million confirmed cases and 800 thousand deaths. Effective treatments to target SARS-CoV-2 are urgently needed. In the present study, we have identified a class of cyclic sulfonamide...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2021-01, Vol.31, p.127667-127667, Article 127667 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 31 |
| creator | Shin, Young Sup Lee, Jun Young Noh, Soojin Kwak, Yoonna Jeon, Sangeun Kwon, Sunoh Jin, Young-hee Jang, Min Seong Kim, Seungtaek Song, Jong Hwan Kim, Hyoung Rae Park, Chul Min |
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Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) continues to spread worldwide, with 25 million confirmed cases and 800 thousand deaths. Effective treatments to target SARS-CoV-2 are urgently needed. In the present study, we have identified a class of cyclic sulfonamide derivatives as novel SARS-CoV-2 inhibitors. Compound 13c of the synthesized compounds exhibited robust inhibitory activity (IC50 = 0.88 μM) against SARS-CoV-2 without cytotoxicity (CC50 > 25 μM), with a selectivity index (SI) of 30.7. In addition, compound 13c exhibited high oral bioavailability (77%) and metabolic stability with good safety profiles in hERG and cytotoxicity studies. The present study identified that cyclic sulfonamide derivatives are a promising new template for the development of anti-SARS-CoV-2 agents. |
| doi_str_mv | 10.1016/j.bmcl.2020.127667 |
| format | Article |
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Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) continues to spread worldwide, with 25 million confirmed cases and 800 thousand deaths. Effective treatments to target SARS-CoV-2 are urgently needed. In the present study, we have identified a class of cyclic sulfonamide derivatives as novel SARS-CoV-2 inhibitors. Compound 13c of the synthesized compounds exhibited robust inhibitory activity (IC50 = 0.88 μM) against SARS-CoV-2 without cytotoxicity (CC50 > 25 μM), with a selectivity index (SI) of 30.7. In addition, compound 13c exhibited high oral bioavailability (77%) and metabolic stability with good safety profiles in hERG and cytotoxicity studies. The present study identified that cyclic sulfonamide derivatives are a promising new template for the development of anti-SARS-CoV-2 agents.</description><identifier>ISSN: 0960-894X</identifier><identifier>ISSN: 1464-3405</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2020.127667</identifier><identifier>PMID: 33160024</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Antiviral Agents - chemical synthesis ; Antiviral Agents - chemistry ; Antiviral Agents - pharmacology ; Cell Line ; Chlorocebus aethiops ; Coronavirus ; COVID-19 Drug Treatment ; Cricetulus ; Cyclic sulfonamide ; Dogs ; Dose-Response Relationship, Drug ; Drug Discovery ; Humans ; Inhibitor ; Mice ; Microbial Sensitivity Tests ; Molecular Structure ; Rats ; SARS-CoV-2 ; SARS-CoV-2 - drug effects ; Structure activity relationship ; Sulfonamides - chemical synthesis ; Sulfonamides - chemistry ; Sulfonamides - pharmacology</subject><ispartof>Bioorganic & medicinal chemistry letters, 2021-01, Vol.31, p.127667-127667, Article 127667</ispartof><rights>2020 Elsevier Ltd</rights><rights>Copyright © 2020 Elsevier Ltd. All rights reserved.</rights><rights>2020 Elsevier Ltd. All rights reserved. 2020 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-ed6325b73f7539b4f4093e5f33af1c4ce19a930e999956c738c390bcc2798afc3</citedby><cites>FETCH-LOGICAL-c455t-ed6325b73f7539b4f4093e5f33af1c4ce19a930e999956c738c390bcc2798afc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X20307782$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33160024$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shin, Young Sup</creatorcontrib><creatorcontrib>Lee, Jun Young</creatorcontrib><creatorcontrib>Noh, Soojin</creatorcontrib><creatorcontrib>Kwak, Yoonna</creatorcontrib><creatorcontrib>Jeon, Sangeun</creatorcontrib><creatorcontrib>Kwon, Sunoh</creatorcontrib><creatorcontrib>Jin, Young-hee</creatorcontrib><creatorcontrib>Jang, Min Seong</creatorcontrib><creatorcontrib>Kim, Seungtaek</creatorcontrib><creatorcontrib>Song, Jong Hwan</creatorcontrib><creatorcontrib>Kim, Hyoung Rae</creatorcontrib><creatorcontrib>Park, Chul Min</creatorcontrib><title>Discovery of cyclic sulfonamide derivatives as potent inhibitors of SARS-CoV-2</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) continues to spread worldwide, with 25 million confirmed cases and 800 thousand deaths. Effective treatments to target SARS-CoV-2 are urgently needed. In the present study, we have identified a class of cyclic sulfonamide derivatives as novel SARS-CoV-2 inhibitors. Compound 13c of the synthesized compounds exhibited robust inhibitory activity (IC50 = 0.88 μM) against SARS-CoV-2 without cytotoxicity (CC50 > 25 μM), with a selectivity index (SI) of 30.7. In addition, compound 13c exhibited high oral bioavailability (77%) and metabolic stability with good safety profiles in hERG and cytotoxicity studies. The present study identified that cyclic sulfonamide derivatives are a promising new template for the development of anti-SARS-CoV-2 agents.</description><subject>Animals</subject><subject>Antiviral Agents - chemical synthesis</subject><subject>Antiviral Agents - chemistry</subject><subject>Antiviral Agents - pharmacology</subject><subject>Cell Line</subject><subject>Chlorocebus aethiops</subject><subject>Coronavirus</subject><subject>COVID-19 Drug Treatment</subject><subject>Cricetulus</subject><subject>Cyclic sulfonamide</subject><subject>Dogs</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Discovery</subject><subject>Humans</subject><subject>Inhibitor</subject><subject>Mice</subject><subject>Microbial Sensitivity Tests</subject><subject>Molecular Structure</subject><subject>Rats</subject><subject>SARS-CoV-2</subject><subject>SARS-CoV-2 - drug effects</subject><subject>Structure activity relationship</subject><subject>Sulfonamides - chemical synthesis</subject><subject>Sulfonamides - chemistry</subject><subject>Sulfonamides - pharmacology</subject><issn>0960-894X</issn><issn>1464-3405</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UV1rFDEUDWKx2-of8EHm0ZdZ8z0bEKGsWoXSglXxLWTu3NgsM5NtMjuw_94sW4t98b4Ebs7H5RxCXjO6ZJTpd5tlO0C_5JSXBW-0bp6RBZNa1kJS9ZwsqNG0Xhn565Sc5byhlEkq5QtyKgTTlHK5INcfQ4Y4Y9pX0Vewhz5AlXe9j6MbQodVhynMbgoz5srlahsnHKcqjHehDVNM-UC7vfh2W6_jz5q_JCfe9RlfPbzn5MfnT9_XX-qrm8uv64urGqRSU42dFly1jfCNEqaVXlIjUHkhnGcgAZlxRlA0ZZSGRqxAGNoC8MasnAdxTj4cdbe7dsAOyk3J9XabwuDS3kYX7NOfMdzZ33G2jS5WXBaBtw8CKd7vME92KEFg37sR4y5bLtWqEarYFSg_QiHFnBP6RxtG7aEIu7GHIuyhCHssopDe_HvgI-Vv8gXw_gjAEtMcMNkMAUfALiSEyXYx_E__D0tsml8</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Shin, Young Sup</creator><creator>Lee, Jun Young</creator><creator>Noh, Soojin</creator><creator>Kwak, Yoonna</creator><creator>Jeon, Sangeun</creator><creator>Kwon, Sunoh</creator><creator>Jin, Young-hee</creator><creator>Jang, Min Seong</creator><creator>Kim, Seungtaek</creator><creator>Song, Jong Hwan</creator><creator>Kim, Hyoung Rae</creator><creator>Park, Chul Min</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210101</creationdate><title>Discovery of cyclic sulfonamide derivatives as potent inhibitors of SARS-CoV-2</title><author>Shin, Young Sup ; Lee, Jun Young ; Noh, Soojin ; Kwak, Yoonna ; Jeon, Sangeun ; Kwon, Sunoh ; Jin, Young-hee ; Jang, Min Seong ; Kim, Seungtaek ; Song, Jong Hwan ; Kim, Hyoung Rae ; Park, Chul Min</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-ed6325b73f7539b4f4093e5f33af1c4ce19a930e999956c738c390bcc2798afc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Antiviral Agents - chemical synthesis</topic><topic>Antiviral Agents - chemistry</topic><topic>Antiviral Agents - pharmacology</topic><topic>Cell Line</topic><topic>Chlorocebus aethiops</topic><topic>Coronavirus</topic><topic>COVID-19 Drug Treatment</topic><topic>Cricetulus</topic><topic>Cyclic sulfonamide</topic><topic>Dogs</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Discovery</topic><topic>Humans</topic><topic>Inhibitor</topic><topic>Mice</topic><topic>Microbial Sensitivity Tests</topic><topic>Molecular Structure</topic><topic>Rats</topic><topic>SARS-CoV-2</topic><topic>SARS-CoV-2 - drug effects</topic><topic>Structure activity relationship</topic><topic>Sulfonamides - chemical synthesis</topic><topic>Sulfonamides - chemistry</topic><topic>Sulfonamides - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shin, Young Sup</creatorcontrib><creatorcontrib>Lee, Jun Young</creatorcontrib><creatorcontrib>Noh, Soojin</creatorcontrib><creatorcontrib>Kwak, Yoonna</creatorcontrib><creatorcontrib>Jeon, Sangeun</creatorcontrib><creatorcontrib>Kwon, Sunoh</creatorcontrib><creatorcontrib>Jin, Young-hee</creatorcontrib><creatorcontrib>Jang, Min Seong</creatorcontrib><creatorcontrib>Kim, Seungtaek</creatorcontrib><creatorcontrib>Song, Jong Hwan</creatorcontrib><creatorcontrib>Kim, Hyoung Rae</creatorcontrib><creatorcontrib>Park, Chul Min</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shin, Young Sup</au><au>Lee, Jun Young</au><au>Noh, Soojin</au><au>Kwak, Yoonna</au><au>Jeon, Sangeun</au><au>Kwon, Sunoh</au><au>Jin, Young-hee</au><au>Jang, Min Seong</au><au>Kim, Seungtaek</au><au>Song, Jong Hwan</au><au>Kim, Hyoung Rae</au><au>Park, Chul Min</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of cyclic sulfonamide derivatives as potent inhibitors of SARS-CoV-2</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>31</volume><spage>127667</spage><epage>127667</epage><pages>127667-127667</pages><artnum>127667</artnum><issn>0960-894X</issn><issn>1464-3405</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) continues to spread worldwide, with 25 million confirmed cases and 800 thousand deaths. Effective treatments to target SARS-CoV-2 are urgently needed. In the present study, we have identified a class of cyclic sulfonamide derivatives as novel SARS-CoV-2 inhibitors. Compound 13c of the synthesized compounds exhibited robust inhibitory activity (IC50 = 0.88 μM) against SARS-CoV-2 without cytotoxicity (CC50 > 25 μM), with a selectivity index (SI) of 30.7. In addition, compound 13c exhibited high oral bioavailability (77%) and metabolic stability with good safety profiles in hERG and cytotoxicity studies. The present study identified that cyclic sulfonamide derivatives are a promising new template for the development of anti-SARS-CoV-2 agents.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33160024</pmid><doi>10.1016/j.bmcl.2020.127667</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology Cell Line Chlorocebus aethiops Coronavirus COVID-19 Drug Treatment Cricetulus Cyclic sulfonamide Dogs Dose-Response Relationship, Drug Drug Discovery Humans Inhibitor Mice Microbial Sensitivity Tests Molecular Structure Rats SARS-CoV-2 SARS-CoV-2 - drug effects Structure activity relationship Sulfonamides - chemical synthesis Sulfonamides - chemistry Sulfonamides - pharmacology |
| title | Discovery of cyclic sulfonamide derivatives as potent inhibitors of SARS-CoV-2 |
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