2-甲基-6-氨基-2H-吲唑 | 50593-30-1

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 中文名称: 2-甲基-6-氨基-2H-吲唑
• 中文别名: 6-氨基-2-甲基吲唑；6-氨基-2-甲基-2H-吲唑
• 英文名称: 2-methyl-2H-indazol-6-amine
• 英文别名: 2-methyl-6-aminoindazole；6-amino-2-methylindazole；2-methylindazol-6-amine；6-Amino-2-methyl-indazol
• CAS: 50593-30-1
• 化学式: C₈H₉N₃
• mdl: MFCD00464866
• 分子量: 147.18
• InChiKey: MHCWLERQNFATHZ-UHFFFAOYSA-N

物化性质

• 熔点：
  148-150
• 沸点：
  354.8±15.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)
• 溶解度：
  <0.1 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2933990090
• 危险性防范说明：
  P280,P305+P351+P338,P310
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  2-甲基-6-氨基-2H-吲唑 在 盐酸 、 碳酸氢钠 、 caesium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 N²-(3-chlorophenyl)-N⁴-methyl-N⁴-(2-methyl-2H-indazol-6-yl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Synthesis and biological evaluation of novel pazopanib derivatives as antitumor agents

  摘要：

  A series of novel pazopanib derivatives, 7a-m, were designed and synthesized by modification of terminal benzene and indazole rings in pazopanib. The structures of all the synthesized compounds were confirmed by H-1 NMR and MS. Their inhibitory activity against VEGFR-2, PDGFR-alpha and c-kit tyrosine kinases were evaluated. All the compounds exhibited definite kinase inhibition, in which compound 7l was most potent with IC50 values of 12 nM against VEGFR-2. Furthermore, compounds 7c, 7d and 7m demonstrated comparable inhibitory activity against three tyrosine kinases to pazopanib, and compound 7f showed superior inhibitory effects than that of pazopanib. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.003
• 作为产物：
  描述：

  2-氨基-4-硝基甲苯 在 盐酸 、 sodium hydride 、 溶剂黄146 、 tin(ll) chloride 、 亚硝酸异戊酯 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 9.5h， 生成 2-甲基-6-氨基-2H-吲唑
  参考文献：
  名称：

  Discovery and synthesis of N2,N4-substitued-cycloalkyl[d]pyrimidine-2,4-diamine analogs: The first examples of small-molecular FGFR-1 activator

  摘要：

  DOI：

  10.1016/j.cclet.2014.06.010

文献信息

• [EN] PYRIMIDINE DERIVATIVES CAPABLE OF INHIBITING ONE OR MORE KINASES<br/>[FR] DÉRIVÉS DE PYRIMIDINE CAPABLES D'INHIBER UNE OU PLUSIEURS KINASES
  申请人：MEDICAL RES COUNCIL

  公开号：WO2009122180A1

  公开（公告）日：2009-10-08

  A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, formula (I): wherein: R1 is C3-8-cycloalkyl; X is O, NR7 or C3-6-heterocycloalkyl; R2 is aryl, heteroaryl, fused or unfused aryl-C3-6-heterocycloalkyl or fused or unfused heteroaryl-C3-6-heterocycIoalkyl, each of which is optionally substituted by one or more substitutents selected from aryl, heteroaryl, C1-6-alkyl, C3-7-cycloalkyl and a group A, wherein said C1-6-alkyl group is optionally substituted by one or more substituents selected from aryl, heteroaryl, R10 and a group A, said heteroaryl group is optionally substituted by one or more R10 groups; and wherein said C3-6-heterocycloalkyl group optionally contains one or more groups selected from oxygen, sulfur, nitrogen and CO; R3 is C1-6-alkyl optionally substituted by one or more substituents selected from aryl, heteroaryl, -NR4R5, -OR6, -NR7(CO)R6, -NR7(CO)NR4R5, -NR7SO2R6, -NR7COOR7, -CONR4R5, C3-6-heterocycloalkyl and formula (a, b, c): wherein R4-7 and A are as defined in the claims. Further aspects relate to the use of said compounds in the treatment of various therapeutic disorders, and more particularly as inhibitors of one or more kinases.

  本发明的第一个方面涉及式(I)的化合物，或其药学上可接受的盐或酯，式(I)如下：其中：R1为C3-8环烷基；X为O、NR7或C3-6杂环烷基；R2为芳基、杂芳基、融合或未融合的芳基-C3-6杂环烷基或融合或未融合的杂芳基-C3-6杂环烷基，每个基可选择地由来自芳基、杂芳基、C1-6烷基、C3-7环烷基和A基的一个或多个取代基取代，其中所述C1-6烷基基可选择地由来自芳基、杂芳基、R10和A基的一个或多个取代基取代，所述杂芳基可选择地由一个或多个R10基取代；以及所述C3-6杂环烷基基可选择地包含一个或多个来自氧、硫、氮和CO的基；R3为C1-6烷基，可选择地由一个或多个来自芳基、杂芳基、-NR4R5、-OR6、-NR7(CO)R6、-NR7(CO)NR4R5、-NR7SO2R6、-NR7COOR7、-CONR4R5、C3-6杂环烷基和式(a, b, c)的取代基取代；其中R4-7和A如权利要求中所定义。进一步方面涉及所述化合物在治疗各种治疗性疾病中的使用，特别是作为一个或多个激酶的抑制剂。
• DIHYDROPYRIDONE UREAS AS P2X7 MODULATORS
  申请人：Brotherton-Pleiss Christine E.

  公开号：US20100160388A1

  公开（公告）日：2010-06-24

  Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n, R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with the P2X7 purinergic receptor.

  公式I的化合物：或其药用可接受的盐，其中m、n、R1、R2、R3、R4和R5按本文件定义。还公开了制造这些化合物的方法以及使用这些化合物治疗与P2X7嘌呤能受体相关疾病的方法。
• [EN] PIPERIDINYL- AND PIPERAZINYL-SUBSTITUTED HETEROAROMATIC CARBOXAMIDES AS MODULATORS OF GPR6<br/>[FR] CARBOXAMIDES HÉTÉROAROMATIQUES SUBSTITUÉS PAR PIPÉRIDINYLE ET PIPÉRAZINYLE EN TANT QUE MODULATEURS DE GPR6
  申请人：TAKEDA PHARMACEUTICALS CO

  公开号：WO2018183145A1

  公开（公告）日：2018-10-04

  Disclosed are compounds of Formula 1 and pharmaceutically acceptable salts thereof, wherein L, R4, R5, R8, R10, R11, X1, X2, X3, X9, X12, and Z are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating diseases, disorders, and conditions associated with GPR6.

  本公开涉及公式1的化合物及其药用可接受的盐，其中L、R4、R5、R8、R10、R11、X1、X2、X3、X9、X12和Z在规范中定义。本公开还涉及制备公式1化合物的材料和方法，包含它们的药物组合物，以及它们用于治疗与GPR6相关的疾病、紊乱和症状的用途。
• Design, synthesis and biological evaluation of novel 2-(4-(1H-indazol-6-yl)-1H-pyrazol-1-yl)acetamide derivatives as potent VEGFR-2 inhibitors
  作者：Xing-Rong Wang、Shuai Wang、Wen-Bo Li、Kai-Yan Xu、Xue-Peng Qiao、Xue-Li Jing、Zi-Xiao Wang、Chang-jiang Yang、Shi-Wu Chen

  DOI：10.1016/j.ejmech.2021.113192

  日期：2021.3

  Vascular endothelial growth factor-2 (VEGFR-2) plays a pivotal role in tumor angiogenesis. Herein, a library of novel 2-(4-(1H-indazol-6-yl)-1H-pyrazol -1-yl)acetamide derivatives were designed and synthesized as VEGFR-2 inhibitors based on scaffold hopping strategy. These compounds exhibited the excellent inhibitory in both VEGFR-2 and tumor cells proliferation. Especially, compound W13 possessed

  血管内皮生长因子2（VEGFR-2）在肿瘤血管生成中起关键作用。在此，基于支架跳跃策略，设计并合成了新颖的2-（4-（1 H-吲唑-6-基）-1 H-吡唑-1-基）乙酰胺衍生物作为VEGFR-2抑制剂。这些化合物对VEGFR-2和肿瘤细胞的增殖均表现出优异的抑制作用。尤其是，化合物W13具有有效的VEGFR-2抑制作用（IC 50  = 1.6 nM）和针对HGC-27肿瘤细胞的抗增殖作用（IC 50  = 0.36±0.11μM），以及对正常GES-1细胞的毒性较小（IC 50  = 50）。 187.46±10.13微米 此外，W13通过调节MMP-9和E-cadherin的表达明显抑制了HGC-27细胞的集落形成，迁移和侵袭，并通过增加ROS的产生和调节细胞凋亡蛋白的表达来诱导HGC-27细胞凋亡。此外，W13阻断了HGC-27细胞中的PI3K-Akt-mTOR信号传导途径。另外，通
• Synthesis and molecular structure of heterocyclic Tröger's bases derived from C-amino heterocycles
  作者：José Cudero、Carmen Pardo、Mar Ramos、Enrique Gutierrez-Puebla、Angeles Monge、José Elguero

  DOI：10.1016/s0040-4020(96)01125-8

  日期：1997.2

  different experimental conditions of formation of Tröger's bases. Amino-azoles and -benzazoles yielded the corresponding Tröger's bases while amino-azines and -benzazines failed to react. The exception was 6-aminoquinoline which yielded the corresponding Tröger's base. When there are two positions of cyclisation the reaction is always regioselective. Tröger's base analogues with pentagonal aromatic frameworks

  允许十四个氨基杂环在Tröger碱基形成的不同实验条件下反应。氨基唑和-苯唑生成相应的Tröger碱，而氨基-嗪和-苯并嗪不能反应。例外的是6-氨基喹啉，产生了相应的Tröger碱。当有两个环化位置时，反应始终是区域选择性的。首次合成了具有五角形芳族骨架的Tröger碱基类似物6b和7b，并确定了7b的X射线分子结构。