{"id":11368,"date":"2022-11-24T03:05:04","date_gmt":"2022-11-23T19:05:04","guid":{"rendered":"https:\/\/www.pyrazoles-derivatives.com\/?p=11368"},"modified":"2022-11-24T03:05:04","modified_gmt":"2022-11-23T19:05:04","slug":"kurasawa-osamus-team-published-research-in-bioorganic-medicinal-chemistry-in-25-cas-1009071-34-4","status":"publish","type":"post","link":"https:\/\/www.pyrazoles-derivatives.com\/?p=11368","title":{"rendered":"Kurasawa, Osamu’s team published research in Bioorganic & Medicinal Chemistry in 25 | CAS: 1009071-34-4"},"content":{"rendered":"

Kurasawa, Osamu published the artcile2-Aminomethylthieno[3,2-d]pyrimidin-4(3H)-ones bearing 3-methylpyrazole hinge binding moiety: Highly potent, selective, and time-dependent inhibitors of Cdc7 kinase<\/i><\/b>, Quality Control of 1009071-34-4<\/a>, the publication is Bioorganic & Medicinal Chemistry (2017), 25(14), 3658-3670, database is CAplus and MEDLINE.<\/p>\n

To increase the success rate for developing new Cdc7 inhibitors for cancer therapy, the authors explored a new chemotype which can comply with the previously-constructed pharmacophore model. Substitution of a pyridine ring of a serendipitously-identified Cdc7 inhibitor 2b (2-methyl-6-(pyridin-4-yl)thieno[3,2-d]pyrimidin-4(3H)-one) with a 3-methylpyrazole resulted in a 4-fold increase in potency and acceptable kinase selectivity, leading to the identification of thieno[3,2-d]pyrimidin-4(3H)-one as an alternative scaffold. Structure-activity relationship (SAR) study revealed that incorporation of a substituted aminomethyl group into the 2-position improved kinase selectivity. Indeed, a pyrrolidinylmethyl derivative 10c (6-(3-methyl-1H-pyrazol-4-yl)-2-(pyrrolidin-1-ylmethyl) thieno[3,2-d]pyrimidin-4(3H)-one) was a potent Cdc7 inhibitor (IC50<\/sub> = 0.70 nM) with high selectivity (Cdk2\/Cdc7\u922e?4,000, ROCK1\/Cdc7=200). It should be noted that 10c exhibited significant time-dependent Cdc7 inhibition with slow dissociation kinetics, cellular pharmacodynamic (PD) effects, and COLO205 growth inhibition. Addnl., mol. basis of high kinase selectivity of 10c is discussed by using the protein structures of Cdc7 and Cdk2.<\/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, Quality Control of 1009071-34-4<\/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, Quality Control of 1009071-34-4<\/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-11368","post","type-post","status-publish","format-standard","hentry","category-1009071-34-4","category-pyrazoles-derivatives","tag-m-w300-350"],"yoast_head":"\nKurasawa, Osamu's team published research in Bioorganic & Medicinal Chemistry in 25 | CAS: 1009071-34-4 | pyrazoles-derivatives<\/title>\n<meta name=\"description\" content=\"Kurasawa, Osamu published the artcile2-Aminomethylthieno[3,2-d]pyrimidin-4(3H)-ones bearing 3-methylpyrazole hinge binding moiety: Highly potent, selective, and time-dependent inhibitors of Cdc7 kinase, Quality Control of 1009071-34-4, the publication is Bioorganic & Medicinal Chemistry (2017), 25(14), 3658-3670, 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=11368\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Kurasawa, Osamu's team published research in Bioorganic & Medicinal Chemistry in 25 | CAS: 1009071-34-4 | pyrazoles-derivatives\" \/>\n<meta property=\"og:description\" content=\"Kurasawa, Osamu published the artcile2-Aminomethylthieno[3,2-d]pyrimidin-4(3H)-ones bearing 3-methylpyrazole hinge binding moiety: Highly potent, selective, and time-dependent inhibitors of Cdc7 kinase, Quality Control of 1009071-34-4, the publication is Bioorganic & Medicinal Chemistry (2017), 25(14), 3658-3670, database is CAplus and MEDLINE.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.pyrazoles-derivatives.com\/?p=11368\" \/>\n<meta property=\"og:site_name\" content=\"pyrazoles-derivatives\" \/>\n<meta property=\"article:published_time\" content=\"2022-11-23T19:05:04+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=11368\",\"url\":\"https:\/\/www.pyrazoles-derivatives.com\/?p=11368\",\"name\":\"Kurasawa, Osamu's team published research in Bioorganic & Medicinal Chemistry in 25 | CAS: 1009071-34-4 | pyrazoles-derivatives\",\"isPartOf\":{\"@id\":\"https:\/\/www.pyrazoles-derivatives.com\/#website\"},\"datePublished\":\"2022-11-23T19:05:04+00:00\",\"author\":{\"@id\":\"https:\/\/www.pyrazoles-derivatives.com\/#\/schema\/person\/d9a9f27bed675392c6f363a01ffd49f1\"},\"description\":\"Kurasawa, Osamu published the artcile2-Aminomethylthieno[3,2-d]pyrimidin-4(3H)-ones bearing 3-methylpyrazole hinge binding moiety: Highly potent, selective, and time-dependent inhibitors of Cdc7 kinase, Quality Control of 1009071-34-4, the publication is Bioorganic & Medicinal Chemistry (2017), 25(14), 3658-3670, database is CAplus and MEDLINE.\",\"breadcrumb\":{\"@id\":\"https:\/\/www.pyrazoles-derivatives.com\/?p=11368#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/www.pyrazoles-derivatives.com\/?p=11368\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/www.pyrazoles-derivatives.com\/?p=11368#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"\u9996\u9875\",\"item\":\"https:\/\/www.pyrazoles-derivatives.com\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Kurasawa, Osamu’s team published research in Bioorganic & Medicinal Chemistry in 25 | 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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