CAS: 1453848-26-4; (S)-1-(1-(4-Chloro-3-Fluorophenyl)-2-Hydroxyethyl)-4-(2-((1-Methyl-1H-Pyrazol-5-yl)Amino)Pyrimidin-4-yl)Pyridin-2(1H)-One
该化合物是针对外细胞信号调控性动脉(ERK)的选择性和强大的小分子抑制器,是MAPK信号路径的关键组成部分,对ERK1和ERK2具有高度的特殊性,表明在临床前型中具有很强的抑制性活动.Ravoxertinib主要被调查其治疗由MAPK路径调控驱动的癌症(如黑素瘤和染色癌)的潜力,其优点包括口服生物利用率,有利的药用动力特性以及克服与上游动脉抑制剂相关的抗药性机制的能力. 该化合物在抑制肿瘤生长和在体外和体外转移方面表现出了希望,从而成为临床进一步发展的候选者.
- 英文名称(S)-1-(1-(4-Chloro-3-Fluorophenyl)-2-Hydroxyethyl)-4-(2-((1-Methyl-1H-Pyrazol-5-yl)Amino)Pyrimidin-4-yl)Pyridin-2(1H)-One
- 中文名称ERK抑制剂
- IUPAC名称(S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one
- CAS编号1453848-26-4
- MFCD编号:MFCD28143918
- FDA UNII编号:R6AXV96CRH
- 分子式:C21H18ClFN6O2分子量:440.87
- 产品CID: 689214
- 同类组份化合物CAS1453848-26-4 (free base)1817728-45-2 (besylate)1817728-47-4 (tosylate)2070009-58-2 (HCl)
- 产品分类生物化工 → 生化试剂 → 激动剂抑制剂
物理性质
- 沸点734.6±70.0 °C(预测)
- 密度1.45±0.1 g/cm3(预测)
- pKa:14.03±0.10(预测)
- PSA:97.86
- LogP:2
- 溶解性≥44.1 mg/mL In DMSO; Insoluble In H2O; ≥19.2 mg/mL In Etoh
- 外观形态白色至黄色固体
- 储存条件储存在 -20°C
- 产品应用该化合物是一种强大的口头可用和选择性的ERK1/2抑制剂(IC50=ERK1-1.1 NM和ERK20.3 NM);它处于第一阶段临床调查中,有效抑制在体外肿瘤细胞中的P90RSK磷酸化;在体内,GDC-094的口服在多种乳腺移植模型中表现出重要的抗抗抗脉搏活动,包括KRAS-MODANT和BRAF-MOMENT-人类肿瘤抗基因转移物,抑制喷口磷化和下游ERK代导信号路径,从而抑制依赖ERK的肿瘤细胞扩散和生存.
上下游产品
(S)-1-(2-((Tert-Butyldimethylsilyl)Oxy)-1-(4-Chloro-3-Fluorophenyl)Ethyl)-4-(2-((1-Methyl-1H-Pyrazol-5-yl)Amino)Pyrimidin-4-yl)Pyridin-2(1H)-One 1453854-96-0(S)-1-(2-(Tert-Butyldimethylsilyloxy)-1-(4-Chloro-3-Fluorophenyl)Ethyl)-4-(2-(Methylthio)Pyrimidin-4-yl)Pyridin-2(1H)-One 1453851-79-0
(S)-1-(2-((Tert-Butyldimethylsilyl)Oxy)-1-(4-Chloro-3-Fluorophenyl)Ethyl)-4-(2-(Methylsulfonyl)Pyrimidin-4-yl)-Pyridin-2(1H)-One 1453851-69-8
合成工艺路线路线简述
📜(S)-1-(2-((Tert-Butyldimethylsilyl)Oxy)-1-(4-Chloro-3-Fluorophenyl)Ethyl)-4-(2-((1-Methyl-1H-Pyrazol-5-yl)Amino)Pyrimidin-4-yl)Pyridin-2(1H)-One置于盐酸体系中,用 甲醇 用作溶剂,化学反应 16.0H,反应生成(S)-1-(1-(4-氯-3-氟苯基)-2-羟乙基)-4-(2-((1-甲基-1H-吡唑-5-基)氨基)嘧啶-4-基)吡啶-2(1H)-酮
参考文献:实用的erk抑制剂gdc-0994的合成
标题:实用的erk抑制剂gdc-0994的合成
摘要:本文报道了以多千克规模生产erk抑制剂gdc-0994的合成路线的工艺开发.通过7个步骤将api制备为相应的苯磺酸盐,总产率为41%.合成路线具有生物催化不对称酮还原,区域选择性吡啶酮s N 2反应和安全且可扩展的钨酸盐催化的硫化物氧化的特征.最终的过程包括望远镜式的s N Ar /去甲硅烷基化/苯磺酸盐的形成过程.最后,Api结晶的发展允许清除与过程相关的杂质,获得> 99.5 A%的HPLC和> 99%ee的目标分子.
Doi:10.1021/acs.Oprd.7B00006
海关参考信息
- 2902600000-乙苯
2903919090-氯苯
2933310010-吡啶
2903991000-对氯甲苯 - 💡 提示：海关信息按照顺序优先匹配，如需确认的海关信息，请参考相关资料。
- 详情请参考：📖 海关编码查询和海关进出口税则
专利信息
专利号:EP-4217339-A1
优先权日:2020-09-26
标题:A process for the synthesis of anthranilic acid/amide compounds and intermediates thereof
专利号:TW-202222162-A
优先权日:2020-09-26
标 题 :A process for the synthesis of anthranilic acid/amide compounds and intermediates thereof
专利号:CA-3191922-A1
优先权日:2020-09-26
标 题:A process for the synthesis of anthranilic acid/amide compounds and intermediates thereof
专利号:IL-301294-A
优先权日:2020-09-26
标题 :A process for the synthesis of anthranilic acid/amide compounds and intermediates thereof
专利号:CN-108379591-B
优先权日:2018-04-03
标 题 :Synthesis of Immune Agonist Targeting Compounds and Their Applications
专利号:CA-2192366-A1
优先权日:1994-06-08
标 题:Genes for the synthesis of antipathogenic substances
供应商参考报价(招募中)
品牌试剂参考报价(招募中)
📌 第三方产品分析报告
主要参考文献
1: Yang MF, Sun SY, Lv HG, Wang WQ, Li HX, Sun JY, Zhang ZY. Ravoxertinib Improves Long-Term Neurologic Deficits after Experimental Subarachnoid Hemorrhage through Early Inhibition of Erk1/2. ACS Omega. 2023 May 23;8(22):19692-19704. doi: 10.1021/acsomega.3c01296. Retraction in: ACS Omega. 2024 Jun 04;9(24):26736. doi: 10.1021/acsomega.4c03199.
2: Yang MF, Sun SY, Lv HG, Wang WQ, Li HX, Sun JY, Zhang ZY. Retraction of "Ravoxertinib Improves Long-Term Neurologic Deficits after Experimental Subarachnoid Hemorrhage through Early Inhibition of Erk1/2". ACS Omega. 2024 Jun 4;9(24):26736. doi: 10.1021/acsomega.4c03199.
3: Janardhan HP, Dresser K, Hutchinson L, Trivedi CM. Pathological MAPK activation-mediated lymphatic basement membrane disruption causes lymphangiectasia that is treatable with ravoxertinib. JCI Insight. 2022 Sep 8;7(17):e153033. doi: 10.1172/jci.insight.153033.
合成参考文献
参考文献:10.1073/pnas.1906824116
摘要:Pegram LM, Liddle JC, Xiao Y, Hoh M, Rudolph J, Iverson DB, Vigers GP, Smith D, Zhang H, Wang W, Moffat JG, Ahn NG. Activation loop dynamics are controlled by conformation-selective inhibitors of ERK2. Proc Natl Acad Sci U S A. 2019 Jul 30;116(31):15463–8.
参考文献:10.1007/s10753-021-01551-7
摘要:Zhou J, Que Y, Pan L, Li X, Zhu C, Jin L, Li S. Supervillin Contributes to LPS-induced Inflammatory Response in THP-1 Cell-derived Macrophages. Inflammation. 2022 Feb;45(1):356–71. doi: 10.1007/s10753-021-01551-7.
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