(Z)-2-(benzo[d]thiazol-2(3H)-ylidene)-2-(2-((2-(pyridin-3-yl)ethyl)amino)pyrimidin-4-yl)acetonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: (Z)-2-(benzo[d]thiazol-2(3H)-ylidene)-2-(2-((2-(pyridin-3-yl)ethyl)amino)pyrimidin-4-yl)acetonitrile
• 英文别名: JNK Inhibitor V；(Z)-2-(benzo[d]thiazol-2[3H]-ylidene)-2-(2-[{2-(pyridin-3-yl)ethyl}amino]pyrimidin-4-yl)acetonitrile；AS601245；2-[(2Z)-2,3-dihydro-1,3-benzothiazol-2-ylidene]-2-(2-{[2-(pyridin-3-yl)ethyl]amino}pyrimidin-4-yl)acetonitrile；(2Z)-2-(3H-1,3-benzothiazol-2-ylidene)-2-[2-(2-pyridin-3-ylethylamino)pyrimidin-4-yl]acetonitrile
• 化学式: C₂₀H₁₆N₆S
• 分子量: 372.453
• InChiKey: AVLYNJZZQYEFEA-XDJHFCHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  7

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	[3H-Benzothiazol-(2Z)-ylidene]-(2-chloro-pyrimidin-4-yl)-acetonitrile	861411-30-5	C13H7ClN4S	286.744

反应信息

• 作为产物：
  描述：

  苯并噻唑-2-乙腈 在 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 1.5h， 生成 (Z)-2-(benzo[d]thiazol-2(3H)-ylidene)-2-(2-((2-(pyridin-3-yl)ethyl)amino)pyrimidin-4-yl)acetonitrile
  参考文献：
  名称：

  Design and Synthesis of the First Generation of Novel Potent, Selective, and in Vivo Active (Benzothiazol-2-yl)acetonitrile Inhibitors of the c-Jun N-Terminal Kinase

  摘要：

  Several lines of evidence support the hypothesis that c-Jun N-terminal kinase (JNKs) plays a critical role in a wide range of diseases including cell death (apoptosis)-related disorders (neurodegenerative diseases, brain, heart, and renal ischemia, epilepsy) and inflammatory disorders (multiple sclerosis, rheumatoid arthritis, inflammatory bowel diseases). Screening of our internal compound collection for inhibitors of JNK3 led to the identification of (benzothiazol-2-yl)acetonitrile derivatives as potent and selective JNK1, -2, -3 inhibitors. Starting from initial hit 1 (AS007149), the chemistry and initial structure-activity relationship (SAR) of this novel and unique kinase inhibitor template were explored. Investigation of the SAR rapidly revealed that the benzothiazol-2-ylacetonitrile pyrimidine core was crucial to retain a good level of potency on rat JNK3. Therefore, compound 6 was further optimized by exploring a number of distal combinations in place of the chlorine atom. This led to the observation that the presence of an aromatic group, two carbons away from the aminopyrimidine moiety and bearing substituents conferring hydrogen bond acceptor (HBA) properties, could improve the potency. Further improvements to the biological and biopharmaceutical profile of the most promising compounds were performed, resulting in the discovery of compound 59 (AS601245). The in vitro and in vivo anti-inflammatory potential of this new JNK inhibitor was investigated and found to demonstrate efficacy per oral route in an experimental model of rheumatoid arthritis (RA).

  DOI：

  10.1021/jm0310986

文献信息

• Modulation of Axon Degeneration
  申请人：Watts Ryan

  公开号：US20110256150A1

  公开（公告）日：2011-10-20

  The invention relates generally to treatment of neurological disorders and nervous system injuries. The invention specifically provides methods of using modulators of particular target proteins to modulate degeneration of neurons or portions thereof, such as axons.
• MODULATION OF AXON DEGENERATION
  申请人：Genentech, Inc.

  公开号：US20140328940A1

  公开（公告）日：2014-11-06

  The invention relates generally to treatment of neurological disorders and nervous system injuries. The invention specifically provides methods of using modulators of particular target proteins to modulate degeneration of neurons or portions thereof, such as axons.
• SYNERGISTIC DRUG COMBINATIONS PREDICTED FROM GENOMIC FEATURES AND SINGLE-AGENT RESPONSE PROFILES
  申请人：THE BROAD INSTITUTE, INC.

  公开号：US20210069230A1

  公开（公告）日：2021-03-11

  The present disclosure relates to discovery of specific synergistic drug combinations and mechanisms of drug resistance. Compositions involving newly-identified drug combinations as well as diagnostic and therapeutic methods related to such discoveries are provided.
• US9101645B2
  申请人：——

  公开号：US9101645B2

  公开（公告）日：2015-08-11
• US9937224B2
  申请人：——

  公开号：US9937224B2

  公开（公告）日：2018-04-10