{"id":10544,"date":"2022-10-26T02:51:49","date_gmt":"2022-10-25T18:51:49","guid":{"rendered":"https:\/\/www.pyrazoles-derivatives.com\/?p=10544"},"modified":"2022-10-26T02:51:49","modified_gmt":"2022-10-25T18:51:49","slug":"tang-guozhi-et-al-published-their-patent-in-2020-cas-153597-59-2","status":"publish","type":"post","link":"https:\/\/www.pyrazoles-derivatives.com\/?p=10544","title":{"rendered":"Tang, Guozhi et al. published their patent in 2020 |CAS: 153597-59-2"},"content":{"rendered":"<p>On July 30, 2020, Tang, Guozhi; Li, Dongbo; Li, Liugen; Zha, Xianchan; Chen, Wenming; Wang, Shaomeng; Yang, Chao-Yie published a patent.<a href=\"https:\/\/www.ambeed.com\/products\/153597-59-2.html\">Formula: C9H12N2O3<\/a> The title of the patent was Preparation of macrocyclic fused pyrazoles as Mcl-1 inhibitors. And the patent contained the following:<\/p>\n<p>The title compounds represented by formula I [R = H or C1-6 alkyl; X = O, S, S(O), S(O)2, or (un)substituted NH; ring A = each (un)substituted 1,3-phenylene or 1,3-naphthalenylene; ring B = arylenyl and heteroarylenyl; ring C = each (un)substituted 1H-pyrazol-3,4-diyl or 1H-pyrazol-4,5-diyl; L1 = [C(R14a)(R14b)]s; L2 = [C(R14c)(R14d)]t; L3 = [C(R14c)(R14f)]v; R14a, R14b, R14d, R14f = each independently H or C1-4 alkyl; s = 2,3,4,5, or 6; t, v = each independently 1,2,3, or 4] or pharmaceutically acceptable salts or solvates thereof are prepared The compounds I are useful for treating a condition or disorder responsive to Mcl-1 inhibition such as cancer, a chronic autoimmune disorder, an inflammatory condition, a proliferative disorder, sepsis, or a viral infection. Thus, Et 7-[2-(bromomethyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-6-chloro-3-[3-[[3-[(4-methoxybenzyl)thio]naphthalen-1-yl]oxy]propyl]-1-methyl-1H-indole-2-carboxylate underwent thioetherification with S-[[5-[[(tert-butyldimethylsilyl)oxy]methyl]-1-methyl-1H-pyrazol-3-yl]methyl] ethanethioate in the presence of K2CO3 in methanol\/THF at room for 1 h to give 27% Et 7-[2-[[[[5-[[(tert-butyldimethylsilyl)oxy]methyl]-1-methyl-1H-pyrazol-3-yl]methyl]thio]methyl]-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-6-chloro-3-[3-[[3-[(4-methoxybenzyl)thio]naphthalen-1-yl]oxy]propyl]-1-methyl-1H-indole-2-carboxylate (II; Ra = 4-methoxybenzyl, Rb = tert-butyldimethylsilyloxy) which was treated with Bu4NF\u00b73H2O in dry THF at room temperature for 2 h to give II (Ra = 4-methoxybenzyl, Rb = HO). Bromination of II (Ra = 4-methoxybenzyl, Rb = HO) with CBr4 and PPh3 in CH2Cl2 at room temperature for 3 h gave II (Ra = 4-methoxybenzyl, Rb = Br) as a brown oil which underwent debenzylation by treatment with triethylsilane and CF3CO2H in CH2Cl2 at room temperature overnight to give II (Ra = H, Rb = Br). Cyclization of II (Ra = H, Rb = Br) by treatment with K2CO3 in acetonitrile at room temperature for 3 h gave macrocyclic 7-(pyrrolo[1,2-b]pyrazol-3-yl)indole-2-carboxylic acid Et ester (III; Rc = Et) which was saponified with a mixture of 2 N aqueous NaOH solution, THF, and MeOH at room temperature for 5 h followed by acidification with 1 N aqueous HCl solution to give III (Rc = H) in 3% over 6 steps. III (Rc = H) showed IC50 of 15 nM against the competitive binding of a fluorescein labeled 21-residue Bid BH3 peptide (residues 79-99) [Swiss-Prot: P55957] to Mcl-1 protein. It showed IC50 of 437 and 123 nM against OPM2 and H929 cell, resp., in a cell viability assay. The experimental process involved the reaction of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate(cas: 153597-59-2).<a href=\"https:\/\/www.ambeed.com\/products\/153597-59-2.html\">Formula: C9H12N2O3<\/a><\/p>\n<p>The Article related to indolyl fused pyrazole macrocyclic compound preparation mcl 1 inhibitor, macrocyclic fused pyrazole preparation mcl 1 inhibitor, cancer chronic autoimmune disorder treatment macrocyclic fused pyrazole preparation, inflammatory condition proliferative disorder macrocyclic fused pyrazole preparation, sepsis viral infection macrocyclic fused pyrazole preparation and other aspects.<a href=\"https:\/\/www.ambeed.com\/products\/153597-59-2.html\">Formula: C9H12N2O3<\/a><\/p>\n<p>Referemce:<br \/><a href=\"https:\/\/en.wikipedia.org\/wiki\/Pyrazole\">Pyrazole &#8211; Wikipedia<\/a>,<br \/><a href=\"https:\/\/www.sciencedirect.com\/topics\/chemistry\/pyrazoles\">Pyrazoles &#8211; an overview | ScienceDirect Topics<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>The Article related to indolyl fused pyrazole macrocyclic compound preparation mcl 1 inhibitor, macrocyclic fused pyrazole preparation mcl 1 inhibitor, cancer chronic autoimmune disorder treatment macrocyclic fused pyrazole preparation, inflammatory condition proliferative disorder macrocyclic fused pyrazole preparation, sepsis viral infection macrocyclic fused pyrazole preparation and other aspects.<a href=\"https:\/\/www.ambeed.com\/products\/153597-59-2.html\">Formula: C9H12N2O3<\/a><\/p>\n","protected":false},"author":8,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[760,131],"tags":[128],"class_list":["post-10544","post","type-post","status-publish","format-standard","hentry","category-153597-59-2","category-pyrazoles-derivatives","tag-100-200"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v24.9 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Tang, Guozhi et al. published their patent in 2020 |CAS: 153597-59-2 | pyrazoles-derivatives<\/title>\n<meta name=\"description\" content=\"On July 30, 2020, Tang, Guozhi; Li, Dongbo; Li, Liugen; Zha, Xianchan; Chen, Wenming; Wang, Shaomeng; Yang, Chao-Yie published a patent.Formula: C9H12N2O3 The title of the patent was Preparation of macrocyclic fused pyrazoles as Mcl-1 inhibitors. And the patent contained the following:\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"http:\/\/www.pyrazoles-derivatives.com\/?p=10544\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Tang, Guozhi et al. published their patent in 2020 |CAS: 153597-59-2 | pyrazoles-derivatives\" \/>\n<meta property=\"og:description\" content=\"On July 30, 2020, Tang, Guozhi; Li, Dongbo; Li, Liugen; Zha, Xianchan; Chen, Wenming; Wang, Shaomeng; Yang, Chao-Yie published a patent.Formula: C9H12N2O3 The title of the patent was Preparation of macrocyclic fused pyrazoles as Mcl-1 inhibitors. And the patent contained the following:\" \/>\n<meta property=\"og:url\" content=\"http:\/\/www.pyrazoles-derivatives.com\/?p=10544\" \/>\n<meta property=\"og:site_name\" content=\"pyrazoles-derivatives\" \/>\n<meta property=\"article:published_time\" content=\"2022-10-25T18:51:49+00:00\" \/>\n<meta name=\"author\" content=\"Jessica.F\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Jessica.F\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"http:\/\/www.pyrazoles-derivatives.com\/?p=10544\",\"url\":\"http:\/\/www.pyrazoles-derivatives.com\/?p=10544\",\"name\":\"Tang, Guozhi et al. published their patent in 2020 |CAS: 153597-59-2 | pyrazoles-derivatives\",\"isPartOf\":{\"@id\":\"http:\/\/www.pyrazoles-derivatives.com\/#website\"},\"datePublished\":\"2022-10-25T18:51:49+00:00\",\"author\":{\"@id\":\"http:\/\/www.pyrazoles-derivatives.com\/#\/schema\/person\/d9a9f27bed675392c6f363a01ffd49f1\"},\"description\":\"On July 30, 2020, Tang, Guozhi; Li, Dongbo; Li, Liugen; Zha, Xianchan; Chen, Wenming; Wang, Shaomeng; Yang, Chao-Yie published a patent.Formula: C9H12N2O3 The title of the patent was Preparation of macrocyclic fused pyrazoles as Mcl-1 inhibitors. And the patent contained the following:\",\"breadcrumb\":{\"@id\":\"http:\/\/www.pyrazoles-derivatives.com\/?p=10544#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"http:\/\/www.pyrazoles-derivatives.com\/?p=10544\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"http:\/\/www.pyrazoles-derivatives.com\/?p=10544#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"\u9996\u9875\",\"item\":\"http:\/\/www.pyrazoles-derivatives.com\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Tang, Guozhi et al. published their patent in 2020 |CAS: 153597-59-2\"}]},{\"@type\":\"WebSite\",\"@id\":\"http:\/\/www.pyrazoles-derivatives.com\/#website\",\"url\":\"http:\/\/www.pyrazoles-derivatives.com\/\",\"name\":\"pyrazoles-derivatives\",\"description\":\"Several pyrazole derivatives possess important pharmacological activities and they have been proved useful materials in drug research. Pyrazole derivatives play an important role in antitumor agents.\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"http:\/\/www.pyrazoles-derivatives.com\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"},{\"@type\":\"Person\",\"@id\":\"http:\/\/www.pyrazoles-derivatives.com\/#\/schema\/person\/d9a9f27bed675392c6f363a01ffd49f1\",\"name\":\"Jessica.F\",\"image\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"http:\/\/www.pyrazoles-derivatives.com\/#\/schema\/person\/image\/\",\"url\":\"https:\/\/cn.cravatar.com\/avatar\/2d1cec2a99eeaad5a5b217c9cdbfb610?s=96&d=mm&r=g\",\"contentUrl\":\"https:\/\/cn.cravatar.com\/avatar\/2d1cec2a99eeaad5a5b217c9cdbfb610?s=96&d=mm&r=g\",\"caption\":\"Jessica.F\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Tang, Guozhi et al. published their patent in 2020 |CAS: 153597-59-2 | pyrazoles-derivatives","description":"On July 30, 2020, Tang, Guozhi; Li, Dongbo; Li, Liugen; Zha, Xianchan; Chen, Wenming; Wang, Shaomeng; Yang, Chao-Yie published a patent.Formula: C9H12N2O3 The title of the patent was Preparation of macrocyclic fused pyrazoles as Mcl-1 inhibitors. And the patent contained the following:","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"http:\/\/www.pyrazoles-derivatives.com\/?p=10544","og_locale":"en_US","og_type":"article","og_title":"Tang, Guozhi et al. published their patent in 2020 |CAS: 153597-59-2 | pyrazoles-derivatives","og_description":"On July 30, 2020, Tang, Guozhi; Li, Dongbo; Li, Liugen; Zha, Xianchan; Chen, Wenming; Wang, Shaomeng; Yang, Chao-Yie published a patent.Formula: C9H12N2O3 The title of the patent was Preparation of macrocyclic fused pyrazoles as Mcl-1 inhibitors. And the patent contained the following:","og_url":"http:\/\/www.pyrazoles-derivatives.com\/?p=10544","og_site_name":"pyrazoles-derivatives","article_published_time":"2022-10-25T18:51:49+00:00","author":"Jessica.F","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Jessica.F","Est. reading time":"3 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"http:\/\/www.pyrazoles-derivatives.com\/?p=10544","url":"http:\/\/www.pyrazoles-derivatives.com\/?p=10544","name":"Tang, Guozhi et al. published their patent in 2020 |CAS: 153597-59-2 | pyrazoles-derivatives","isPartOf":{"@id":"http:\/\/www.pyrazoles-derivatives.com\/#website"},"datePublished":"2022-10-25T18:51:49+00:00","author":{"@id":"http:\/\/www.pyrazoles-derivatives.com\/#\/schema\/person\/d9a9f27bed675392c6f363a01ffd49f1"},"description":"On July 30, 2020, Tang, Guozhi; Li, Dongbo; Li, Liugen; Zha, Xianchan; Chen, Wenming; Wang, Shaomeng; Yang, Chao-Yie published a patent.Formula: C9H12N2O3 The title of the patent was Preparation of macrocyclic fused pyrazoles as Mcl-1 inhibitors. And the patent contained the following:","breadcrumb":{"@id":"http:\/\/www.pyrazoles-derivatives.com\/?p=10544#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["http:\/\/www.pyrazoles-derivatives.com\/?p=10544"]}]},{"@type":"BreadcrumbList","@id":"http:\/\/www.pyrazoles-derivatives.com\/?p=10544#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"\u9996\u9875","item":"http:\/\/www.pyrazoles-derivatives.com\/"},{"@type":"ListItem","position":2,"name":"Tang, Guozhi et al. published their patent in 2020 |CAS: 153597-59-2"}]},{"@type":"WebSite","@id":"http:\/\/www.pyrazoles-derivatives.com\/#website","url":"http:\/\/www.pyrazoles-derivatives.com\/","name":"pyrazoles-derivatives","description":"Several pyrazole derivatives possess important pharmacological activities and they have been proved useful materials in drug research. Pyrazole derivatives play an important role in antitumor agents.","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"http:\/\/www.pyrazoles-derivatives.com\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"},{"@type":"Person","@id":"http:\/\/www.pyrazoles-derivatives.com\/#\/schema\/person\/d9a9f27bed675392c6f363a01ffd49f1","name":"Jessica.F","image":{"@type":"ImageObject","inLanguage":"en-US","@id":"http:\/\/www.pyrazoles-derivatives.com\/#\/schema\/person\/image\/","url":"https:\/\/cn.cravatar.com\/avatar\/2d1cec2a99eeaad5a5b217c9cdbfb610?s=96&d=mm&r=g","contentUrl":"https:\/\/cn.cravatar.com\/avatar\/2d1cec2a99eeaad5a5b217c9cdbfb610?s=96&d=mm&r=g","caption":"Jessica.F"}}]}},"_links":{"self":[{"href":"https:\/\/www.pyrazoles-derivatives.com\/index.php?rest_route=\/wp\/v2\/posts\/10544","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.pyrazoles-derivatives.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.pyrazoles-derivatives.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.pyrazoles-derivatives.com\/index.php?rest_route=\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/www.pyrazoles-derivatives.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=10544"}],"version-history":[{"count":0,"href":"https:\/\/www.pyrazoles-derivatives.com\/index.php?rest_route=\/wp\/v2\/posts\/10544\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.pyrazoles-derivatives.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=10544"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.pyrazoles-derivatives.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=10544"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.pyrazoles-derivatives.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=10544"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}