(5-t-butyl-oxazol-2-ylmethyl)-phosphonic acid diethyl ester | 352533-38-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (5-t-butyl-oxazol-2-ylmethyl)-phosphonic acid diethyl ester
• 英文别名: 5-tert-butyl-2-(diethoxyphosphorylmethyl)-1,3-oxazole
• CAS: 352533-38-1
• 化学式: C₁₂H₂₂NO₄P
• 分子量: 275.285
• InChiKey: HTELQMVUNZOYJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  61.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (5-t-butyl-oxazol-2-ylmethyl)-phosphonic acid diethyl ester 在 盐酸 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 反应 3.17h， 生成 2-amino-5-[(E)-2-(5-t-butyl-oxazol-2-yl)-vinyl]-thiazole
  参考文献：
  名称：

  [EN] INHIBITORS OF CYCLIN-DEPENDENT KINASES
  [FR] INHIBITEURS DE KINASES CYCLINE-DÉPENDANTES

  摘要：

  公开号：

  WO2017044858A3
• 作为产物：
  描述：

  5-叔丁基-2-(氯甲基)恶唑 以 甲苯 、 亚磷酸三乙酯 为溶剂， 以98%的产率得到(5-t-butyl-oxazol-2-ylmethyl)-phosphonic acid diethyl ester
  参考文献：
  名称：

  Carbon substituted aminothiazole inhibitors of cyclin dependent kinases

  摘要：

  提供了该式化合物及其药用可接受的盐。

  公开号：

  US06407124B1

文献信息

• Discovery of MFH290: A Potent and Highly Selective Covalent Inhibitor for Cyclin-Dependent Kinase 12/13
  作者：Yao Liu、Mingfeng Hao、Alan L. Leggett、Yang Gao、Scott B. Ficarro、Jianwei Che、Zhixiang He、Calla M. Olson、Jarrod A. Marto、Nicholas P. Kwiatkowski、Tinghu Zhang、Nathanael S. Gray

  DOI：10.1021/acs.jmedchem.9b01929

  日期：2020.7.9

  but selective inhibition of endogenous CDK12 is difficult. Here, we report the development of MFH290, a novel cysteine (Cys)-directed covalent inhibitor of CDK12/13. MFH290 forms a covalent bond with Cys-1039 of CDK12, exhibits excellent kinome selectivity, inhibits the phosphorylation of serine-2 in the C-terminal domain (CTD) of RNA-polymerase II (Pol II), and reduces the expression of key DNA damage

  细胞周期蛋白依赖性激酶12（CDK12）的遗传耗竭或类似物敏感性CDK12的选择性抑制可降低DNA损伤修复基因的表达，但内源性CDK12的选择性抑制却很困难。在这里，我们报告MFH290，CDK12 / 13的新型半胱氨酸（Cys）定向共价抑制剂的发展。MFH290与CDK12的Cys-1039形成共价键，表现出优异的激酶组选择性，抑制RNA聚合酶II（Pol II）C端结构域（CTD）中丝氨酸2的磷酸化，并降低关键DNA的表达损伤修复基因。重要的是，这些作用被证明是依赖CDK12的，因为Cys-1039的突变使该激酶对MFH290无效，并恢复了Pol II CTD磷酸化和DNA损伤修复基因的表达。与其对DNA损伤修复基因表达的影响一致，
• 3-Aminopyrazole inhibitors of cyclin dependent kinases
  申请人：——

  公开号：US20010047019A1

  公开（公告）日：2001-11-29

  The present invention describes compounds of formula I 1 and pharmaceutically acceptable salts thereof. The formula I compounds are protein kinase inhibitors and are useful in the treatment of proliferative diseases, for example, cancer, inflammation and arthritis. They may also be useful in the treatment of Alzheimer's disease, and cardiovascular disease.

  本发明描述了I1式化合物及其药学上可接受的盐。I1式化合物是蛋白激酶抑制剂，可用于治疗增生性疾病，例如癌症、炎症和关节炎。它们还可能对治疗阿尔茨海默病和心血管疾病有用。
• 3-aminopyrazole inhibitors of cyclin dependent kinases
  申请人：——

  公开号：US20030018058A1

  公开（公告）日：2003-01-23

  The present invention describes compounds of formula I 1 and pharmaceutically acceptable salts thereof. The formula I compounds are protein kinase inhibitors and are useful in the treatment of proliferative diseases, for example, cancer, inflammation and arthritis. They may also be useful in the treatment of Alzheimer's disease, and cardiovascular disease.

  本发明描述了I1式化合物及其药学上可接受的盐。I1式化合物是蛋白激酶抑制剂，可用于治疗增生性疾病，如癌症、炎症和关节炎。它们也可能对治疗阿尔茨海默病和心血管疾病有用。
• INHIBITORS OF CYCLIN-DEPENDENT KINASES
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：EP4019515A1

  公开（公告）日：2022-06-29

  The present invention provides novel compounds of Formulae (I'), (I), (II'), and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., CDK7, CDK12, or CDK13), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

  本发明提供了式(I')、(I)、(II')和(II)的新型化合物及其药学上可接受的盐、溶液剂、水合物、多晶型、共晶体、同分异构体、立体异构体、同位素标记的衍生物、原药及其组合物。还提供了涉及本发明化合物或组合物的方法和试剂盒，用于治疗和/或预防增殖性疾病（如癌症（如、白血病、急性淋巴细胞白血病、淋巴瘤、伯基特淋巴瘤、黑色素瘤、多发性骨髓瘤、乳腺癌、尤文氏肉瘤、骨肉瘤、脑癌、卵巢癌、神经母细胞瘤、肺癌、结直肠癌）、良性肿瘤、与血管生成相关的疾病、炎症性疾病、自身炎症性疾病和自身免疫性疾病）的方法和试剂盒。使用本发明的化合物或组合物治疗患有增殖性疾病的受试者，可抑制激酶的异常活性，如细胞周期蛋白依赖性激酶（CDK）（如CDK7、CDK12或CDK13），从而诱导细胞凋亡和/或抑制受试者的转录。
• Inhibitors of cyclin-dependent kinases
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US11142507B2

  公开（公告）日：2021-10-12

  The present invention provides novel compounds of Formulae (I′), (I), (II′), and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., CDK7, CDK12, or CDK13), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

  本发明提供了式(I′)、(I)、(II′)和(II)的新型化合物及其药学上可接受的盐、溶液剂、水合物、多晶型、共晶体、同系物、立体异构体、同位素标记的衍生物、原药及其组合物。还提供了涉及本发明化合物或组合物的方法和试剂盒，用于治疗和/或预防增殖性疾病（如癌症（如、白血病、急性淋巴细胞白血病、淋巴瘤、伯基特淋巴瘤、黑色素瘤、多发性骨髓瘤、乳腺癌、尤文氏肉瘤、骨肉瘤、脑癌、卵巢癌、神经母细胞瘤、肺癌、结直肠癌）、良性肿瘤、与血管生成相关的疾病、炎症性疾病、自身炎症性疾病和自身免疫性疾病）的方法和试剂盒。使用本发明的化合物或组合物治疗患有增殖性疾病的受试者，可抑制激酶的异常活性，如细胞周期蛋白依赖性激酶（CDK）（如CDK7、CDK12或CDK13），从而诱导细胞凋亡和/或抑制受试者的转录。