6-[5-(5-tert-Butyl-oxazol-2-ylmethylsulfanyl)-thiazol-2-ylamino]-pyridine-3-carbaldehyde | 350510-44-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-[5-(5-tert-Butyl-oxazol-2-ylmethylsulfanyl)-thiazol-2-ylamino]-pyridine-3-carbaldehyde
• 英文别名: 6-[[5-[(5-Tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]amino]pyridine-3-carbaldehyde
• CAS: 350510-44-0
• 化学式: C₁₇H₁₈N₄O₂S₂
• 分子量: 374.488
• InChiKey: JULXXHVMQWWNRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  134
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-氨基-2,2-二甲基-1-丙醇 、 6-[5-(5-tert-Butyl-oxazol-2-ylmethylsulfanyl)-thiazol-2-ylamino]-pyridine-3-carbaldehyde 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 以70%的产率得到BMS-357075
  参考文献：
  名称：

  Synthesis and biological activity of N-aryl-2-aminothiazoles: potent pan inhibitors of cyclin-dependent kinases

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2004.02.105
• 作为产物：
  描述：

  5-叔丁基-2-(氯甲基)恶唑 在 sodium hydroxide 、 叔丁基氯化镁 、 叔丁基锂 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.5h， 生成 6-[5-(5-tert-Butyl-oxazol-2-ylmethylsulfanyl)-thiazol-2-ylamino]-pyridine-3-carbaldehyde
  参考文献：
  名称：

  Synthesis and biological activity of N-aryl-2-aminothiazoles: potent pan inhibitors of cyclin-dependent kinases

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2004.02.105

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。
• 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
• US6262096B1
  申请人：——

  公开号：US6262096B1

  公开（公告）日：2001-07-17
• US6521759B2
  申请人：——

  公开号：US6521759B2

  公开（公告）日：2003-02-18
• [EN] AMINOTHIAZOLE INHIBITORS OF CYCLIN DEPENDENT KINASES<br/>[FR] INHIBITEURS AMINOTHIAZOLES DE KINASES DEPENDANTES DE LA CYCLINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2001044217A1

  公开（公告）日：2001-06-21

  Compounds of formula (I) and pharmaceutically acceptable salts thereof. As used in formula (I), and throughout the specification, the symbols have the following meanings: R1 and R2 are independently hydrogen, fluorine or alkyl; R3 is aryl or heteroaryl, R4 has various meanings; R5 is hydrogen or alkyl; m is an integer of 0 to 2; and n is an integer of 1 to 3. The compounds of formula (I) are protein kinase inhibitors and are useful in the treatment and prevention of proliferative diseases, for example, cancer, inflammation and arthritis. They may also be useful in the treatment of neurodegenerative diseases such as Alzheimer's diseases cardiovascular diseases, viral diseases and fungal diseases.