{"id":11622,"date":"2022-12-01T06:36:54","date_gmt":"2022-11-30T22:36:54","guid":{"rendered":"https:\/\/www.pyrazoles-derivatives.com\/?p=11622"},"modified":"2022-12-01T06:36:54","modified_gmt":"2022-11-30T22:36:54","slug":"katoh-taisukes-team-published-research-in-bioorganic-medicinal-chemistry-in-24-cas-1009071-34-4","status":"publish","type":"post","link":"https:\/\/www.pyrazoles-derivatives.com\/?p=11622","title":{"rendered":"Katoh, Taisuke’s team published research in Bioorganic & Medicinal Chemistry in 24 | CAS: 1009071-34-4"},"content":{"rendered":"

Katoh, Taisuke published the artcileDiscovery and optimization of 1,7-disubstituted-2,2-dimethyl-2,3-dihydroquinazolin-4(1H)-ones as potent and selective PKC\u03b8 inhibitors<\/i><\/b>, Category: pyrazoles-derivatives<\/a>, the publication is Bioorganic & Medicinal Chemistry (2016), 24(11), 2466-2475, database is CAplus and MEDLINE.<\/p>\n

A high-throughput screening campaign helped us to identify an initial lead compound (1) as a protein kinase C-\u03b8 (PKC\u03b8) inhibitor. Using the docking model of compound 1 bound to PKC\u03b8 as a model, structure-based drug design was employed and two regions were identified that could be explored for further optimization, i.e., (a) a hydrophilic region around Thr442, unique to PKC family, in the inner part of the hinge region, and (b) a lipophilic region at the forefront of the Et moiety. Optimization of the hinge binder led us to find 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one as a potent and selective hinge binder, which resulted in the discovery of compound 5. Filling the lipophilic region with a suitable lipophilic substituent boosted PKC\u03b8 inhibitory activity and led to the identification of compound 10. The co-crystal structure of compound 10 bound to PKC\u03b8 confirmed that both the hydrophilic and lipophilic regions were fully utilized. Further optimization of compound 10 led us to compound 14, which demonstrated an improved pharmacokinetic profile and inhibition of IL-2 production in a mouse.<\/p>\n

Bioorganic & Medicinal Chemistry published new progress about 1009071-34-4. 1009071-34-4 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester, name is tert-Butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate, and the molecular formula is C15H25BN2O4, Category: pyrazoles-derivatives<\/a>.<\/p>\n

Referemce:
https:\/\/en.wikipedia.org\/wiki\/Pyrazole<\/a>,
Pyrazoles – an overview | ScienceDirect Topics<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Bioorganic & Medicinal Chemistry published new progress about 1009071-34-4. 1009071-34-4 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester, name is tert-Butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate, and the molecular formula is C15H25BN2O4, Category: pyrazoles-derivatives<\/a>.<\/p>\n","protected":false},"author":8,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[810,131],"tags":[811],"class_list":["post-11622","post","type-post","status-publish","format-standard","hentry","category-1009071-34-4","category-pyrazoles-derivatives","tag-m-w300-350"],"yoast_head":"\nKatoh, Taisuke's team published research in Bioorganic & Medicinal Chemistry in 24 | CAS: 1009071-34-4 | pyrazoles-derivatives<\/title>\n<meta name=\"description\" content=\"Katoh, Taisuke published the artcileDiscovery and optimization of 1,7-disubstituted-2,2-dimethyl-2,3-dihydroquinazolin-4(1H)-ones as potent and selective PKC\u03b8 inhibitors, Category: pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry (2016), 24(11), 2466-2475, database is CAplus and MEDLINE.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.pyrazoles-derivatives.com\/?p=11622\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Katoh, Taisuke's team published research in Bioorganic & Medicinal Chemistry in 24 | CAS: 1009071-34-4 | pyrazoles-derivatives\" \/>\n<meta property=\"og:description\" content=\"Katoh, Taisuke published the artcileDiscovery and optimization of 1,7-disubstituted-2,2-dimethyl-2,3-dihydroquinazolin-4(1H)-ones as potent and selective PKC\u03b8 inhibitors, Category: pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry (2016), 24(11), 2466-2475, database is CAplus and MEDLINE.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.pyrazoles-derivatives.com\/?p=11622\" \/>\n<meta property=\"og:site_name\" content=\"pyrazoles-derivatives\" \/>\n<meta property=\"article:published_time\" content=\"2022-11-30T22:36:54+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=\"1 minute\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/www.pyrazoles-derivatives.com\/?p=11622\",\"url\":\"https:\/\/www.pyrazoles-derivatives.com\/?p=11622\",\"name\":\"Katoh, Taisuke's team published research in Bioorganic & Medicinal Chemistry in 24 | CAS: 1009071-34-4 | pyrazoles-derivatives\",\"isPartOf\":{\"@id\":\"https:\/\/www.pyrazoles-derivatives.com\/#website\"},\"datePublished\":\"2022-11-30T22:36:54+00:00\",\"author\":{\"@id\":\"https:\/\/www.pyrazoles-derivatives.com\/#\/schema\/person\/d9a9f27bed675392c6f363a01ffd49f1\"},\"description\":\"Katoh, Taisuke published the artcileDiscovery and optimization of 1,7-disubstituted-2,2-dimethyl-2,3-dihydroquinazolin-4(1H)-ones as potent and selective PKC\u03b8 inhibitors, Category: pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry (2016), 24(11), 2466-2475, database is CAplus and MEDLINE.\",\"breadcrumb\":{\"@id\":\"https:\/\/www.pyrazoles-derivatives.com\/?p=11622#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/www.pyrazoles-derivatives.com\/?p=11622\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/www.pyrazoles-derivatives.com\/?p=11622#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"\u9996\u9875\",\"item\":\"https:\/\/www.pyrazoles-derivatives.com\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Katoh, Taisuke’s team published research in Bioorganic & Medicinal Chemistry in 24 | CAS: 1009071-34-4\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/www.pyrazoles-derivatives.com\/#website\",\"url\":\"https:\/\/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. 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