CAS: 1801765-04-7; (3S,4S)-8-(6-Amino-5-((2-Amino-3-Chloropyridin-4-yl)Thio)Pyrazin-2-yl)-3-Methyl-2-Oxa-8-Azaspiro[4.5]Decan-4-Amine

N-Boc-4-哌啶甲酸乙酯置于盐酸,Titanium(Iv) Tetraethanolate,锂硼氢,正丁基锂,四丁基氟化铵,Sodium Hydride,戴斯-马丁氧化剂,二异丙胺,N,N-二异丙基乙胺,对甲苯磺酰氯体系中,用 四氢呋喃,1,4-二氧六环,正己烷,二氯甲烷,二甲基亚砜 用作溶剂,化学反应 62.5H,反应生成(3S,4S)-8-(6-氨基-5-((2-氨基-3-氯吡啶基-4-基)硫代)吡嗪-2-基)-3-甲基-2-氧杂-8-氮杂螺[4.5]癸-4-胺
参考文献:鉴定tno155,一种变构shp2抑制剂,用于治疗癌症.
标题:鉴定tno155,一种变构shp2抑制剂,用于治疗癌症.
摘要:Shp2是由ptpn11编码的非受体蛋白酪氨酸磷酸酶基因并通过mapk信号通路参与细胞生长和分化.Shp2在程序性细胞死亡途径(pd-1 / Pd-L1)中也起着重要作用.作为癌蛋白以及潜在的免疫调节剂,控制shp2活性具有很高的治疗意义.作为针对shp2的全面计划的一部分,我们鉴定了多种抑制变构结合的方式,并并行优化了许多化学支架.在此药物注释报告中,我们详细介绍了变构shp2抑制剂吡嗪类的鉴定和优化.基于结构和特性的药物设计使蛋白质-配体相互作用,有效的细胞抑制,理化,药物和选择性特性的控制以及体内的有效作用得以鉴定抗肿瘤活性.这些研究最终发现了tno155,(3 S,4 S)-8-(6-氨基-5-((2-氨基-3-氯吡啶-4-基)硫代吡嗪-2-基)-3-Methyl-2-Oxa-8-Azaspiro [4.5] Decan-4-Amine(1),一种有效的,选择性的,口服有效的,一
Doi:10.1021/acs.Jmedchem.0C01170

专利信息

专利号:US-2025101006-A1
优先权日:2022-01-31
标题:Process for the synthesis of pyrazolyl derivatives useful as anti-cancer agents
发明人：BAENZIGER MARKUS; GALLOU FABRICE; GUO FENGFENG; HÄNGGI RUDOLF; HAN ENJIAN; JORDINE GUIDO; LI JIALIANG; LIU WEIPENG; MIAO BUKEYAN; RONG SHAOFENG; SANTANDREA ERNESTO; SCHIRNER PAUL BERND; SHEN XIAODONG; WANG CAN; ZHANG HAO
权利人:NOVARTIS AG
摘要:The invention provides a novel process, novel process steps and novel intermediates useful in the synthesis of pharmaceutically active compounds, especially KRAS G12C inhibitors. The present invention provides a direct enantioselective chemical manufacturing method of making Compound A, or a pharmaceutically acceptable hydrate or solvent thereof: (I). The invention provides a process for preparing Intermediate B6* comprising reacting Intermediate B4* with Intermediate B5* in an atroposelective coupling reaction, using a chiral catalyst.

专利号:WO-2023143605-A1
优先权日:2022-01-31
标 题:Process for the synthesis of pyrazolyl derivatives useful as anti-cancer agents

专利号:EP-4472969-A1
优先权日:2022-01-31
标 题 :Process for the synthesis of pyrazolyl derivatives useful as anti-cancer agents

专利号:CN-118871436-A
优先权日:2022-01-31
标 题 :Synthesis of pyrazolyl derivatives useful as anticancer agents

专利号:WO-2023071314-A1
优先权日:2021-10-29
标 题:Synthesis, preparation method and use of shp2 and cdk4/6 dual-target inhibitory compound

专利号:US-12331058-B2
优先权日:2021-10-29
标 题:SHP2 and CDK4/6 dual-target inhibitory compound and pharmaceutical composition containing the same
发明人：WU XIAOXING; CHEN XIAOYU; LI WENQIANG; Shu Chengxia; LUO GUANGMEI; YANG KEXIN
权利人:UNIV CHINA PHARMA
摘要:The present invention belongs to the field of medicinal chemistry, and particularly relates to synthesis, a preparation method and the use of an inhibitor containing dual targets SHP2 and CDK4/6, wherein the inhibitor comprises three compounds of general formulas I-III and pharmaceutically acceptable salts, enantiomers, diastereomers, tautomers, solvates, polymorphs or prodrugs thereof. According to the present invention, a class of brand-new SHP2 and CDK4/6 dual-target inhibitors are prepared by means of a pharmacophore fusion and reasonable drug design method, so that the problems of drug resistance, poor drug effect, etc., of the existing SHP2 inhibitor and CDK4/6 inhibitor are solved; the great significance of the present invention is providing the first SHP2 and CDK4/6 dual-target inhibitor, which provides a basis for solving the problem of drug resistance of kinase and phosphatase in the later period.