2-((2-溴噻唑-5-基硫代)-甲基)-5-叔丁基噁唑 | 350511-08-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: 2-((2-溴噻唑-5-基硫代)-甲基)-5-叔丁基噁唑
• 英文名称: 2-(((2-bromothiazol-5-yl)thio)methyl)-5-(tert-butyl)oxazole
• 英文别名: 2-{[(2-Bromo-1,3-thiazol-5-yl)sulfanyl]methyl}-5-tert-butyl-1,3-oxazole；2-[(2-bromo-1,3-thiazol-5-yl)sulfanylmethyl]-5-tert-butyl-1,3-oxazole
• CAS: 350511-08-9
• 化学式: C₁₁H₁₃BrN₂OS₂
• 分子量: 333.273
• InChiKey: PWNRQULKRBVIPO-UHFFFAOYSA-N

物化性质

• 沸点：
  391.4±27.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  92.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-((2-溴噻唑-5-基硫代)-甲基)-5-叔丁基噁唑 在 吡啶 、 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 3.0h， 生成 (S)-(3-(5-((5-tert-butyloxazol-2-yl)methylthio)thiazol-2-ylamino)piperidine-1-yl)(4-nitrophenyl)methanone
  参考文献：
  名称：

  MFH290的发现：细胞周期蛋白依赖性激酶12/13的强效高选择性共价抑制剂。

  摘要：

  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，

  DOI：

  10.1021/acs.jmedchem.9b01929
• 作为产物：
  描述：

  2-氨基噻唑-5-基硫氰酸酯 在 亚硝酸特丁酯 、 copper(ll) bromide 作用下， 反应 2.0h， 以33%的产率得到2-((2-溴噻唑-5-基硫代)-甲基)-5-叔丁基噁唑
  参考文献：
  名称：

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

  摘要：

  公开号：

  WO2017044858A3

文献信息

• Aminothiazole inhibitors of cyclin dependent kinases
  申请人：——

  公开号：US20020137778A1

  公开（公告）日：2002-09-26

  The present invention describes compounds of formula I: 1 and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , m and n are as defined in the specification. The compounds of formula I 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, chemotherapy-induced alopecia, and cardiovascular disease.

  本发明描述了I式化合物及其药学上可接受的盐，其中R1、R2、R3、R4、R5、m和n如规范中所定义。I式化合物是蛋白激酶抑制剂，可用于治疗增殖性疾病，例如癌症、炎症和关节炎。它们还可以用于治疗阿尔茨海默病、化疗引起的脱发和心血管疾病。
• 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。
• A diaminocyclohexyl analog of SNS-032 with improved permeability and bioavailability properties
  作者：Ingrid C. Choong、Iana Serafimova、Junfa Fan、David Stockett、Erica Chan、Sravanthi Cheeti、Yafan Lu、Bruce Fahr、Phuongly Pham、Michelle R. Arkin、Duncan H. Walker、Ute Hoch

  DOI：10.1016/j.bmcl.2008.09.073

  日期：2008.11

  The identification of a selective CDK2, 7, 9 inhibitor 4 with improved permeability is described. Compound 4 exhibits comparable CDK selectivity profile to SNS-032, but shows improved permeability and higher bioavailability in mice. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis and biological activity of N-aryl-2-aminothiazoles: potent pan inhibitors of cyclin-dependent kinases
  作者：Raj N. Misra、Hai-yun Xiao、David K. Williams、Kyoung S. Kim、Songfeng Lu、Kristen A. Keller、Janet G. Mulheron、Roberta Batorsky、John S. Tokarski、John S. Sack、S.David Kimball、Francis Y. Lee、Kevin R. Webster

  DOI：10.1016/j.bmcl.2004.02.105

  日期：2004.6

  N-Aryl aminothiazoles 6-9 were prepared from 2-bromothiazole 5 and found to be CDK inhibitors. In cells they act as potent cytotoxic agents. Selectivity for CDK1, CDK2, and CDK4 was dependent of the nature of the N-aryl group and distinct from the CDK2 selective N-acyl analogues. The N-2-pyridyl analogues 7 and 19 showed pan CDK inhibitory activity. Elaborated analogues 19 and 23 exhibited anticancer activity in mice against P388 murine leukemia. The solid-state structure of 7 bound to CDK2 shows a similar binding mode to the N-acyl analogues. (C) 2004 Elsevier Ltd. All rights reserved.
• AMINOTHIAZOLE INHIBITORS OF CYCLIN DEPENDENT KINASES
  申请人：Bristol-Myers Squibb Co.

  公开号：EP1240153A1

  公开（公告）日：2002-09-18