4-(N'-benzhydrylidene-hydrazino)-5-cyanothiophene-2-carboxylic acid methyl ester | 648412-61-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(N'-benzhydrylidene-hydrazino)-5-cyanothiophene-2-carboxylic acid methyl ester
• 英文别名: methyl 5-cyano-4-[2-(diphenylmethylene)hydrazino]-thiophene-2-carboxylate；methyl 5-cyano-4-[2-(diphenylmethylene)hydrazino]thiophene-2-carboxylate；Methyl 5-cyano-4-[2-(diphenylmethylene)hydrazinyl]-2-thiophenecarboxylate；methyl 4-(2-benzhydrylidenehydrazinyl)-5-cyanothiophene-2-carboxylate
• CAS: 648412-61-7
• 化学式: C₂₀H₁₅N₃O₂S
• 分子量: 361.424
• InChiKey: CDCCPWZFPXXFPU-UHFFFAOYSA-N

物化性质

• 沸点：
  544.9±60.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  甲醇 、 4-(N'-benzhydrylidene-hydrazino)-5-cyanothiophene-2-carboxylic acid methyl ester 在 盐酸 、 水 、 硫酸 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 10.0h， 以63%的产率得到3-氨基-1H-噻吩[3,2-C]吡唑-5-羧酸甲酯
  参考文献：
  名称：

  Thieno[3,2-c]pyrazoles: A novel class of Aurora inhibitors with favorable antitumor activity

  摘要：

  A novel series of 3-amino-1H-thieno[3,2-c]pyrazole derivatives demonstrating high potency in inhibiting Aurora kinases was developed. Here we describe the synthesis and a preliminary structure-activity relationship, which led to the discovery of a representative compound (38), which showed low nanomolar inhibitory activity in the anti-proliferation assay and was able to block the cell cycle in HCT-116 cell line. This compound demonstrated favorable pharmacokinetic properties and good efficacy in the HL-60 xenograft tumor model.

  DOI：

  10.1016/j.bmc.2010.07.048
• 作为产物：
  描述：

  4-溴-5-氰基噻吩-2-羧酸甲酯 、 二苯甲酮腙 在 1,1'-双(二苯基膦)二茂铁 、 palladium diacetate caesium carbonate 作用下， 以 甲苯 为溶剂， 反应 16.0h， 以83.4%的产率得到4-(N'-benzhydrylidene-hydrazino)-5-cyanothiophene-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Heterobicyclic pyrazole derivatives as kinase inhibitors

  摘要：

  公开了如规范中定义的化学式（I）的双环吡唑及其药用盐，其制备方法以及包含它们的药物组合物；本发明的化合物在治疗中可能有用，用于治疗与异常蛋白激酶活性相关的疾病，如癌症。

  公开号：

  US20060160874A1

文献信息

• Heterobicyclic pyrazole derivatives as kinase inhibitors
  申请人：Tonani Roberto

  公开号：US20060160874A1

  公开（公告）日：2006-07-20

  Bicyclo-pyrazoles of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.

  公开了如规范中定义的化学式（I）的双环吡唑及其药用盐，其制备方法以及包含它们的药物组合物；本发明的化合物在治疗中可能有用，用于治疗与异常蛋白激酶活性相关的疾病，如癌症。
• [EN] HETEROBICYCLIC PYRAZOLE DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DERIVES DE PYRAZOLE HETEROBICYCLIQUES UTILISES COMME INHIBITEURS DE KINASE
  申请人：PHARMACIA ITALIA SPA

  公开号：WO2004007504A1

  公开（公告）日：2004-01-22

  Bicyclo-pyrazoles of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.

  公开了规范中定义的化学式(I)的双环吡唑及其药用盐，其制备方法和包含它们的药物组合物；发明中的化合物可能在治疗中对治疗与蛋白激酶活性失调相关的疾病，如癌症，具有用处。
• Pyrazole derivatives as TNIK, IKKϵ and TBK1 inhibitor and pharmaceutical composition comprising same
  申请人：GREEN CROSS CORPORATION

  公开号：US10294207B2

  公开（公告）日：2019-05-21

  Provided is pyrazole derivatives as a TNIK (Traf2- and NCK-interacting kinase), IKKε (I-kappa-B kinase epsilon) and TBK1 (TANK-binding kinase 1) inhibitor; the pyrazole derivative according to the present invention effectively inhibits TNIK, IKKε and TBK1, and thus is useful not only as an anticancer agent for the treatment of various cancers including colorectal cancer, breast cancer, CNS cancer, colon cancer, non-small cell lung cancer, kidney cancer, prostate cancer, ovarian cancer, uterus cancer, stomach cancer, liver cancer, skin cancer, lung cancer, brain cancer, bladder cancer, esophageal cancer, pancreatic cancer, thyroid cancer, head and neck cancer, squamous cell carcinoma, osteosarcoma, B-cell or T-cell lymphoma, acute or chronic leukemia and multiple myeloma, but as a therapeutic agent for chronic inflammation.

  本发明提供了吡唑衍生物作为 TNIK（Traf2-和 NCK-相互作用激酶）、IKKε（I-kappa-B 激酶 epsilon）和 TBK1（TANK 结合激酶 1）抑制剂；根据本发明的吡唑衍生物可有效抑制 TNIK、IKKε 和 TBK1，因此不仅可作为抗癌剂用于治疗各种癌症，包括结直肠癌、乳腺癌、中枢神经系统癌、结肠癌、非小细胞肺癌、肾癌、前列腺癌、卵巢癌、子宫癌、胃癌、乳腺癌、结肠癌、非小细胞肺癌、肾癌、前列腺癌、卵巢癌、子宫癌、胃癌、结肠癌、非小细胞肺癌、子宫癌、胃癌、肝癌、皮肤癌、肺癌、脑癌、膀胱癌、食道癌、胰腺癌、甲状腺癌、头颈部癌、鳞状细胞癌、骨肉瘤、B 细胞或 T 细胞淋巴瘤、急性或慢性白血病和多发性骨髓瘤，还可作为慢性炎症的治疗剂。
• HETEROBICYCLIC PYRAZOLE DERIVATIVES AS KINASE INHIBITORS
  申请人：Pharmacia Italia S.p.A.

  公开号：EP1534716A1

  公开（公告）日：2005-06-01
• PYRAZOLE DERIVATIVES AS TNIK, IKKe AND TBK1 INHIBITOR AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
  申请人：GREEN CROSS CORPORATION

  公开号：US20160289196A1

  公开（公告）日：2016-10-06

  Provided is pyrazole derivatives as a TNIK (Traf2- and NCK-interacting kinase), IKKε (I-kappa-B kinase epsilon) and TBK1 (TANK-binding kinase 1) inhibitor; the pyrazole derivative according to the present invention effectively inhibits TNIK, IKKε and TBK1, and thus is useful not only as an anticancer agent for the treatment of various cancers including colorectal cancer, breast cancer, CNS cancer, colon cancer, non-small cell lung cancer, kidney cancer, prostate cancer, ovarian cancer, uterus cancer, stomach cancer, liver cancer, skin cancer, lung cancer, brain cancer, bladder cancer, esophageal cancer, pancreatic cancer, thyroid cancer, head and neck cancer, squamous cell carcinoma, osteosarcoma, B-cell or T-cell lymphoma, acute or chronic leukemia and multiple myeloma, but as a therapeutic agent for chronic inflammation.