(3-Methyl-1H-pyrazol-1-YL)acetonitrile | 113336-25-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (3-Methyl-1H-pyrazol-1-YL)acetonitrile
• 英文别名: 2-(3-methylpyrazol-1-yl)acetonitrile
• CAS: 113336-25-7
• 化学式: C₆H₇N₃
• 分子量: 121.142
• InChiKey: KJTZQQSHCZIVAL-UHFFFAOYSA-N

物化性质

• 沸点：
  110-123 °C(Press: 13 Torr)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  41.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3-Methyl-1H-pyrazol-1-YL)acetonitrile 在 盐酸羟胺 作用下， 以 乙醇 为溶剂， 反应 13.0h， 生成 4-(3-Methylpyrazol-1-yl)-1,2-oxazol-5-amine
  参考文献：
  名称：

  Aminoisoxazoles as Potent Inhibitors of Tryptophan 2,3-Dioxygenase 2 (TDO2)

  摘要：

  Tryptophan 2,3-dioxygenase 2 (TDO2) catalyzes the conversion of tryptophan to the immunosuppressive metabolite kynurenine. TDO2 overexpression has been observed in a number of cancers; therefore, TDO inhibition may be a useful therapeutic intervention for cancers. We identified an aminoisoxazole series as potent TDO2 inhibitors from a high-throughput screen (HTS). An extensive medicinal chemistry effort revealed that both the amino group and the isoxazole moiety are important for TDO2 inhibitory activity. Computational modeling yielded a binding hypothesis and provided insight into the observed structure-activity relationships. The optimized compound 21 is a potent TDO2 inhibitor with modest selectivity over indolamine 2,3-dioxygenase 1 (IDOL) and with improved human whole blood stability.

  DOI：

  10.1021/acsmedchemlett.7b00427
• 作为产物：
  描述：

  3-甲基吡唑 、 氯乙腈 在 caesium carbonate 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 (3-Methyl-1H-pyrazol-1-YL)acetonitrile
  参考文献：
  名称：

  Aminoisoxazoles as Potent Inhibitors of Tryptophan 2,3-Dioxygenase 2 (TDO2)

  摘要：

  Tryptophan 2,3-dioxygenase 2 (TDO2) catalyzes the conversion of tryptophan to the immunosuppressive metabolite kynurenine. TDO2 overexpression has been observed in a number of cancers; therefore, TDO inhibition may be a useful therapeutic intervention for cancers. We identified an aminoisoxazole series as potent TDO2 inhibitors from a high-throughput screen (HTS). An extensive medicinal chemistry effort revealed that both the amino group and the isoxazole moiety are important for TDO2 inhibitory activity. Computational modeling yielded a binding hypothesis and provided insight into the observed structure-activity relationships. The optimized compound 21 is a potent TDO2 inhibitor with modest selectivity over indolamine 2,3-dioxygenase 1 (IDOL) and with improved human whole blood stability.

  DOI：

  10.1021/acsmedchemlett.7b00427

文献信息

• Discovery of a Novel Series of Potent SHP2 Allosteric Inhibitors
  作者：Alessia Petrocchi、Alessandro Grillo、Luca Ferrante、Pietro Randazzo、Adolfo Prandi、Marilenia De Matteo、Costanza Iaccarino、Monica Bisbocci、Antonella Cellucci、Cristina Alli、Martina Nibbio、Vincenzo Pucci、Jérôme Amaudrut、Christian Montalbetti、Carlo Toniatti、Romano Di Fabio

  DOI：10.1021/acsmedchemlett.3c00059

  日期：2023.5.11

  drug discovery program aimed at obtaining novel allosteric SHP2 inhibitors, a series of pyrazopyrazine derivatives bearing an original bicyclo[3.1.0]hexane basic moiety on the left-hand side region of the molecule were identified. We report herein the discovery process, the in vitro pharmacological profile, and the early developability features of compound 25, one of the most potent members of the

  含Src同源2的蛋白酪氨酸磷酸酶2（SHP2）是第一个报道的非受体致癌酪氨酸磷酸酶，连接多个信号转导级联并通过PD-1检查点受体发挥免疫抑制功能。作为旨在获得新型变构 SHP2 抑制剂的药物发现计划的一部分，鉴定了一系列在分子左侧区域带有原始双环[3.1.0]己烷碱性部分的吡唑吡嗪衍生物。我们在此报告了化合物25 （该系列中最有效的成员之一）的发现过程、体外药理学概况和早期可开发特征。
• [EN] PYRAZOLO[1,5-A]PYRAZIN-4-YL DERIVATIVES AS JAK-INHIBITORS<br/>[FR] DÉRIVÉS PYRAZOLO[1,5-A]PYRAZIN-4-YLE COMME INHIBITEURS JAC
  申请人：PFIZER

  公开号：WO2017144995A1

  公开（公告）日：2017-08-31

  A compound compound having the structure (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein A, A' and A" are independently O, C=O, C-R' or N-R", where R' and R" may independently be H, amino, -NR7COR6, COR6, -CONR7R8, C1-C6 alkyl, or hydroxy(C1-C6 alkyl), and R" may be present or absent, and is present where the rules of valency permit, and where not more than one of A, A' and A" is O or C=0; R0 and R are independently H, Br, CI, F, or C1-C6 alkyl; R1 is H, C1-C6 alkyl, or hydroxy(C1-C6 alkyl); R2 is selected from the group consisting of H, C1-C6 alkyl, C1-C6 alkoxy, hydroxy(C1-C6 alkyl), phenyl(C1-C6 alkyl), formyl, heteroaryl, heterocyclic, -COR6, -OCOR6, -COOR6, -NR7COR6, -CONR7R8, and -(CH2)n-W, where W is cyano, hydroxy, C3-C8 cycloalkyl, -SO2NR7R8, and -SO2-R9, where R9 is C1-C6 alkyl, C3-C8 cycloalkyl, heteroaryl, or heterocyclic; wherein each of said alkyl, cycloalkyl, heterocyclic, or heteroaryl may be unsubstituted or substituted by halo, cyano, hydroxy, or C1-C6 alkyl; X is C-R3 or N, where R3 may be H or C1-C6 alkyl; R4 and R5 are independently H, amino, C1-C6 alkyl, or hydroxy(C1-C6 alkyl); R6, R7 and R8 are each independently H, C1-C6 alkyl, C1-C4 alkoxy(C1-C6 alkyl), or C3-C8 cycloalkyl, said C1- C6 alkyl is optionally substituted by halo, CN or hydroxy; or, R7 and R8 together with the atom bonded thereto form a 5- or 6-membered ring, said ring being optionally substituted by halo, hydroxy, CN, or C1-C6 alkyl; and, n is 0, 1, 2 or 3. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations thereof with other therapeutic agents.
• Aminoisoxazoles as Potent Inhibitors of Tryptophan 2,3-Dioxygenase 2 (TDO2)
  作者：Zhonghua Pei、Rohan Mendonca、Lewis Gazzard、Richard Pastor、Leanne Goon、Amy Gustafson、Erica VanderPorten、Georgia Hatzivassiliou、Kevin Dement、Robert Cass、Po-wai Yuen、Yamin Zhang、Guosheng Wu、Xingyu Lin、Yichin Liu、Benjamin D. Sellers

  DOI：10.1021/acsmedchemlett.7b00427

  日期：2018.5.10

  Tryptophan 2,3-dioxygenase 2 (TDO2) catalyzes the conversion of tryptophan to the immunosuppressive metabolite kynurenine. TDO2 overexpression has been observed in a number of cancers; therefore, TDO inhibition may be a useful therapeutic intervention for cancers. We identified an aminoisoxazole series as potent TDO2 inhibitors from a high-throughput screen (HTS). An extensive medicinal chemistry effort revealed that both the amino group and the isoxazole moiety are important for TDO2 inhibitory activity. Computational modeling yielded a binding hypothesis and provided insight into the observed structure-activity relationships. The optimized compound 21 is a potent TDO2 inhibitor with modest selectivity over indolamine 2,3-dioxygenase 1 (IDOL) and with improved human whole blood stability.