(1-methyl-1H-benzo[d]imidazol-5-yl)methanamine | 747409-26-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: (1-methyl-1H-benzo[d]imidazol-5-yl)methanamine
• 英文别名: (1-Methylbenzimidazol-5-yl)methanamine
• CAS: 747409-26-3
• 化学式: C₉H₁₁N₃
• 分子量: 161.206
• InChiKey: DWRIYGGJCVRRHI-UHFFFAOYSA-N

物化性质

• 沸点：
  335.6±34.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1-methyl-1H-benzo[d]imidazol-5-yl)methanamine 在 N-(benzyloxy)-N-(pivaloyloxy)-4-(trifluoromethyl)benzamide 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 40.0h， 生成 1-methyl-5-(2-(pyridin-3-yl)ethyl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  通过氮删除的 C−C 偶联：在库合成中的应用

  摘要：

  采用（杂）芳香醛和（杂）芳基甲基胺作为结构单元，异头酰胺作为试剂的还原胺化-“氮缺失”反应序列用于化合物库的平行合成。该方法可以访问与早期药物发现计划相关的超过 50 万种化合物的化学空间。

  DOI：

  10.1002/chem.202203470

文献信息

• MASP-2 INHIBITORS AND METHODS OF USE
  申请人：Omeros Corporation

  公开号：US20210171531A1

  公开（公告）日：2021-06-10

  The present disclosure provides, inter alia, compounds with MASP-2 inhibitory activity, compositions of such compounds, and methods of making and using such compounds.

  本公开提供了具有MASP-2抑制活性的化合物，这些化合物的组合物，以及制造和使用这些化合物的方法。
• Chemical compounds
  申请人：——

  公开号：US20030225094A1

  公开（公告）日：2003-12-04

  Compounds of the general structural formula (I) and use of the compounds and salts and solvates thereof, as therapeutic agents. 1

  通用结构式（I）的化合物及其盐和溶剂合物的用途，作为治疗剂。
• [EN] ADENINE DERIVATIVES AS PROTEIN KINASE INHIBITORS<br/>[FR] DÉRIVÉS D'ADÉNINE EN TANT QU'INHIBITEURS DE PROTÉINE KINASES
  申请人：BCI PHARMA

  公开号：WO2017191297A1

  公开（公告）日：2017-11-09

  The present invention relates to a compound suitable for use as a kinase inhibitor according to general formula (I) [compound (C), herein after], or the N- oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof, formula (I) wherein A, R1, R2, R3, R3', R4, R4', X, Y, Z, T are as defined in the claims. The invention further relates to an in vitro method of inhibiting protein kinase activity which comprises contacting a protein kinase with a compound of formula (I), or the N-oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof. The invention further relates to the compounds of formula (I) per se, as well as to their use as a medicament, and for use or in a method of treatment of a disease mediated by a protein kinase selected from cancer, inflammatory disorders, cardiovascular diseases, viral induced diseases, circulatory diseases, fibro-proliferative diseases and pain sensitization disorders.

  本发明涉及一种适用于作为激酶抑制剂的化合物，其符合一般式(I) [化合物(C)，以下简称]，或其N-氧化物、药学上可接受的盐、药学上可接受的溶剂，或其立体异构体，式(I)中A、R1、R2、R3、R3'、R4、R4'、X、Y、Z、T的定义如权利要求所述。本发明还涉及一种体外抑制蛋白激酶活性的方法，包括将蛋白激酶与式(I)的化合物，或其N-氧化物、药学上可接受的盐、药学上可接受的溶剂，或其立体异构体接触。本发明还涉及式(I)的化合物本身，以及其作为药物的用途，以及用于治疗由蛋白激酶介导的疾病的方法，所述疾病包括癌症、炎症性疾病、心血管疾病、病毒感染性疾病、循环系统疾病、纤维增殖性疾病和疼痛敏化性疾病。
• [EN] SUBSTITUTED 4-(1-PYRROLIDINYL)PYRIMIDINE COMPOUNDS AS DIMERIZATION INHIBITORS OF NEURONAL NITRIC OXIDE SYNTHASE<br/>[FR] COMPOSÉS DE 4-(1-PYRROLIDINYL)PYRIMIDINE SUBSTITUÉS EN TANT QU'INHIBITEURS DE LA DIMÉRISATION DE L'OXYDE NITRIQUE SYNTHASE NEURONALE
  申请人：UNIV NORTHWESTERN

  公开号：WO2017214286A1

  公开（公告）日：2017-12-14

  Disclosed are compounds, pharmaceutical compositions comprising the compounds, and methods of using the compounds and pharmaceutical compositions for treating a subject in need thereof. The disclosed compounds may be described as substituted 4-(1-pyrrolidinyl)pyrimidine compounds. The disclosed compounds are shown to inhibit the activity of nitric oxide synthases (NOSs) including neuronal NOS (nNOS) by inhibiting dimerization, and as such, the disclosed compounds and pharmaceutical compositions may be utilized in methods for treating a subject having or at risk for developing a disease or disorder that is associated with nNOS activity.

  揭示了化合物、含有这些化合物的药物组合物以及使用这些化合物和药物组合物治疗需要的受试者的方法。所揭示的化合物可以描述为取代的4-(1-吡咯啉基)嘧啶化合物。所揭示的化合物被证明能通过抑制二聚化来抑制一氧化氮合酶（NOSs）的活性，包括神经元NOS（nNOS），因此，这些化合物和药物组合物可用于治疗患有或有风险发展与nNOS活性相关的疾病或紊乱的受试者的方法。
• [EN] 4-[[(7-AMINOPYRAZOLO[1,5-A]PYRIMIDIN-5-YL)AMINO]METHYL]PIPERIDIN-3-OL COMPOUNDS AND THEIR THERAPEUTIC USE<br/>[FR] COMPOSÉS DE 4-[[(7-AMINOPYRAZOLO[1,5-A]PYRIMIDIN-5-YL)AMINO]MÉTHYL]PIPÉRIDIN-3-OL ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：CARRICK THERAPEUTICS LTD

  公开号：WO2021122745A1

  公开（公告）日：2021-06-24

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain H-APPAMP compounds (referred to herein as "H-APPAMP compounds") that, inter alia, inhibit cyclin-dependent protein kinases (CDKs), especially CDK12 and/or CDK13, and are selective, for example, for CDK12 and/or CDK13 as compared to CDK7. In addition to selectively inhibiting CDK12 and/or CDK13, the compounds also act as selective Cyclin K degraders thereby removing the key signaling mechanism required for CDK12 and/or CDK13 activation; this confers additional cellular potency and selectivity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK, especially CDK12 and/or CDK13; and to treat disorders including: disorders that are associated with CDK, especially CDK12 and/or CDK13; disorders that result from an inappropriate activity of a CDK, especially CDK12 and/or CDK13; disorders that are associated with CDK mutation, especially CDK12 and/or CDK13mutation; disorders that are associated with CDK overexpression, especially CDK12 and/or CDK13 overexpression; disorders that are associated with upstream pathway activation of CDK, especially CDK12 and/or CDK13; disorders that are ameliorated by the inhibition of CDK, especially CDK12 and/or CDK13; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; cardiovascular disorders (including atherosclerosis); autoimmune disorders (including rheumatoid arthritis); and disorders caused by dysfunction of translation in cells (including muscular dystrophy). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti estrogen, an anti-androgen, a Her2 blocker, a cytotoxic chemotherapeutic agent, an agent stimulating the immune system, a checkpoint inhibitor, a DMA repair inhibitor, etc.

  本发明一般涉及治疗化合物领域。更具体地，本发明涉及某些H-APPAMP化合物（以下简称为“H-APPAMP化合物”），其中包括抑制细胞周期依赖性蛋白激酶（CDKs），特别是CDK12和/或CDK13，并且具有选择性，例如与CDK7相比，对CDK12和/或CDK13有选择性。除了选择性地抑制CDK12和/或CDK13外，这些化合物还作为选择性的Cyclin K降解物，从而去除了CDK12和/或CDK13激活所需的关键信号机制；这赋予了额外的细胞效力和选择性。本发明还涉及包含这些化合物的药物组合物，以及使用这些化合物和组合物，无论是在体外还是在体内，来抑制CDK，特别是CDK12和/或CDK13；以及治疗包括以下疾病的疾病：与CDK有关的疾病，特别是与CDK12和/或CDK13有关的疾病；由于CDK不恰当活性导致的疾病，特别是由于CDK12和/或CDK13不恰当活性导致的疾病；与CDK突变有关的疾病，特别是与CDK12和/或CDK13突变有关的疾病；与CDK过度表达有关的疾病，特别是与CDK12和/或CDK13过度表达有关的疾病；与CDK上游途径激活有关的疾病，特别是与CDK12和/或CDK13上游途径激活有关的疾病；通过抑制CDK改善的疾病，特别是通过抑制CDK12和/或CDK13改善的疾病；增生性疾病；癌症；病毒感染（包括HIV）；神经退行性疾病（包括阿尔茨海默病和帕金森病）；缺血；肾脏疾病；心血管疾病（包括动脉粥样硬化）；自身免疫性疾病（包括类风湿性关节炎）；以及由细胞中翻译功能失调引起的疾病（包括肌肉萎缩症）的疾病。可选地，治疗进一步包括与另一活性药剂的治疗（例如同时或顺序治疗），该药剂可以是芳香化酶抑制剂、抗雌激素、抗雄激素、Her2阻断剂、细胞毒化疗药物、刺激免疫系统的药剂、检查点抑制剂、DNA修复抑制剂等。