2-氯-4-甲基-(9ci)-1H-苯并咪唑 | 15965-57-8

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 2-氯-4-甲基-(9ci)-1H-苯并咪唑
• 中文别名: 2-氯-4-甲基-1H-苯并咪唑
• 英文名称: 2-chloro-4-methyl-1H-benzo[d]imidazole
• 英文别名: 2-chloro-4-methyl-1H-benzimidazole；2-Chloro-4-methylbenzimidazole
• CAS: 15965-57-8
• 化学式: C₈H₇ClN₂
• 分子量: 166.61
• InChiKey: SYUSWWBZZRCZGH-UHFFFAOYSA-N

物化性质

• 沸点：
  339.9±35.0 °C(Predicted)
• 密度：
  1.351

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-氯-4-甲基-(9ci)-1H-苯并咪唑 在 一水合肼 作用下， 生成 2-肼基-4-甲基-1H-苯并咪唑
  参考文献：
  名称：

  Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs

  摘要：

  A series of 1-aryl-3,4-substituted-1H-pyrazol-5-ol derivatives was synthesized and evaluated as prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors to obtain a novel anti-prostate cancer drug. After modifying 1-(1H-benzimidazol-2-yl)-3,4-dimethyl-1H-pyrazol-5-ol (1), a hit compound found during random screening using a recombinant PCA-1/ALKBH3, 1-(1H-5-methylbenzimidazol-2-yl)-4-benzyl-3-methyl-1H- pyrazol-5-ol (35, HUHS015), was obtained as a potent PCA-1/ALKBH3 inhibitor both in vitro and in vivo. The bioavailability (BA) of 35 was 7.2% in rats after oral administration. As expected, continuously administering 35 significantly suppressed the growth of DU145 cells, which are human hormone-independent prostate cancer cells, in a mouse xenograft model without untoward effects. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.008
• 作为产物：
  描述：

  4-甲基苯并咪唑酮 在 三氯氧磷 作用下， 反应 16.0h， 以26%的产率得到2-氯-4-甲基-(9ci)-1H-苯并咪唑
  参考文献：
  名称：

  通过虚拟筛选发现选择性Aurora A激酶抑制剂

  摘要：

  在这里，我们报告发现了Aurora A选择性抑制剂的发现，Aurora A是细胞分裂和潜在抗癌靶标的关键调节剂。我们使用原子类别扩展配体重叠评分（xLOS），这是我们小组最近开发的一种基于3D配体的虚拟筛选方法，用于选择437种参考激酶抑制剂的形状和药效基团类似物。生化筛选发现了两个激酶抑制剂系列中空前的支架抑制剂系列。其中一种已通过基于结构的设计成功优化为有效的Aurora A抑制剂（IC 50= 2 nM），对Aurora激酶具有非常高的激酶组选择性。该抑制剂将Aurora A锁定为非活性构象，并破坏与其激活蛋白TPX2的结合，从而削弱Aurora A在有丝分裂纺锤体上的定位并诱导细胞分裂缺陷。该表型可以通过抗抑制剂的Aurora A突变体挽救。此外，该抑制剂在细胞中不诱导Aurora B特异性作用。

  DOI：

  10.1021/acs.jmedchem.6b00709

文献信息

• [EN] QUINUCLIDINE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS<br/>[FR] COMPOSÉS QUINUCLIDINE EN TANT QUE LIGANDS DU RÉCEPTEUR NICOTINIQUE ALPHA-7 DE L'ACÉTYLCHOLINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2016073407A1

  公开（公告）日：2016-05-12

  There are disclosed a series of quinuclidines having the Formula (I). which bind to the nicotinic α7 receptor and may be useful for the treatment of disorders of the central nervous system.

  揭示了一系列具有化学式（I）的喹诺啉类化合物，它们与尼古丁型α7受体结合，可能对中枢神经系统疾病的治疗有用。
• Heterocyclic amines having central nervous system activity
  申请人：The Upjohn Company

  公开号：US05273975A1

  公开（公告）日：1993-12-28

  Tricyclic nitrogen containing compounds, having central nervous system activity of the following structural formula: ##STR1## and pharmaceutically acceptable salts thereof wherein R.sub.1, R.sub.2, and R.sub.3 are independently hydrogen, C.sub.1-6 alkyl, alkenyl, or alkynyl, C.sub.3-10 cycloalkyl, or R.sub.1 and R.sub.2 are joined to form a C.sub.3-7 cyclic amine which can contain additional heteroatoms; X is hydrogen, C.sub.1-6 alkyl halogen, hydroxy, alkoxy, cyano, carboxamide, carboxyl, or carboalkoxyl; A is SO.sub.2, N, CH, CH.sub.2, CHCH.sub.3, C.dbd.O, C.dbd.S, C-SCH.sub.3, C.dbd.NH, C-NH.sub.2, C-NHCH.sub.3, C--NHCOOCH.sub.3, or C--NHCN. B is CH.sub.2, CH, C.dbd.O, N, NH or N--CH.sub.3 ; n is 0 or 1; and D is CH, CH.sub.2, C.dbd.O, O, N, NH or N--CH.sub.3. These new compounds are suitable for treating schizophrenia, Parkinson's disease, anxiety, depression or as compounds for lowering blood pressure in animal or human hosts.

  三环氮含化合物，具有以下结构式的中枢神经系统活性：##STR1##及其药学上可接受的盐，其中R.sub.1、R.sub.2和R.sub.3独立地是氢、C.sub.1-6烷基、烯基或炔基、C.sub.3-10环烷基，或R.sub.1和R.sub.2连接形成可含有额外杂原子的C.sub.3-7环胺；X是氢、C.sub.1-6烷基卤素、羟基、烷氧基、氰基、羧酰胺、羧基或羧烷氧基；A是SO.sub.2、N、CH、CH.sub.2、CHCH.sub.3、C.dbd.O、C.dbd.S、C-SCH.sub.3、C.dbd.NH、C-NH.sub.2、C-NHCH.sub.3、C--NHCOOCH.sub.3或C--NHCN。B是CH.sub.2、CH、C.dbd.O、N、NH或N--CH.sub.3；n为0或1；D是CH、CH.sub.2、C.dbd.O、O、N、NH或N--CH.sub.3。这些新化合物适用于治疗精神分裂症、帕金森病、焦虑、抑郁或作为降低动物或人类宿主血压的化合物。
• [EN] PIPERIDINE-AMINO-BENZIMIDAZOLE DERIVATIVES AS INHIBITORS OF RESPIRATORY SYNCYTIAL VIRUS REPLICATION<br/>[FR] DERIVES PIPERIDINE-AMINO-BENZIMIDAZOLE EN TANT QU'INHIBITEURS DE LA REPLICATION DU VIRUS RESPIRATOIRE SYNCYTIAL
  申请人：TIBOTEC PHARM LTD

  公开号：WO2005058873A1

  公开（公告）日：2005-06-30

  The present invention concerns piperidine-amino-benzimidazoles having inhibitory activity on the replication of the respiratory syncytial virus and having the formula (I) their prodrugs, N-oxides, addition salts, quaternary amines, metal complexes and stereochemically isomeric forms wherein Q is C1-6alkyl optionally substituted with trifluorornethyl, C3-7cycloalkyl, Ar2, hydroxy, C1-4 alkoxy, C1-4alkylthio, Ar2-oxy-, Ar2-thio-, Ar2(CH2)noxy, Ar2(CH2)nthio, hydroxycarbonyl, aminocarbonyl, C1-4alkyl­carbonyl, Ar2carbonyl, C1-4alkoxycarbonyl, Ar2(CH2)ncarbonyl, aminocarbonyloxy, C1-4alkylcarbonyloxy, Ar2carbonyloxy, Ar2(CH2)ncarbonyloxy, C1-4alkoxy­ carbonyl(CH2)noxy, mono- or di(C1-4alkyl)aminocarbonyl, mono- or di(C1-4alkyl)-­aminocarbonyloxy, aminosulfonyl, mono-odi(C1-4alkyl)aminosulfonyl or a heterocycles selected from the group consisting of pyrrolidinyl, pyrrolyl, dihydropyrrolyl, imidazolyl, triazolyl, piperidinyl, homopiperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxothiomorpholinyl, pyridyl and tetrahydropyridyl, wherein each of said heterocycle may optionally be substituted with oxo or C1-6alkyl; G is a direct bond or optionally substituted Cl-10 loalkanediyl; R1 is Ar1 or a monocyclic or bicyclic heterocycle; one of R2a and R3a is C1-6 salkyl and the other one of R2a and R3a is hydrogen; in case R2a is different from hydrogen then R2b is hydrogen or C1-6alkyl, and R3b is hydrogen; in case R3a is different from hydrogen then R3b is hydrogen or C1-6alkyl, and R2b is hydrogen; t is 1, 2 or 3; Ar1 is phenyl or substituted phenyl; and Ar2 is phenyl or substituted phenyl. It further concerns their preparation and compositions comprising them, as well as their use as a medicine.

  本发明涉及具有抑制呼吸道合胞病毒复制活性的哌啶-氨基-苯并咪唑类化合物，其具有通式(I)，及其前药、N-氧化物、加成盐、季铵盐、金属络合物和立体化学异构体，其中Q为C1-6烷基，可选择性地被三氟甲基、C3-7环烷基、Ar2、羟基、C1-4烷氧基、C1-4烷基硫基、Ar2-氧-、Ar2-硫-、Ar2(CH2)n氧、Ar2(CH2)n硫、羟基羰基、氨基羰基、C1-4烷基羰基、Ar2羰基、C1-4烷氧基羰基、Ar2(CH2)n羰基、氨基羰基氧、C1-4烷基羰基氧、Ar2羰基氧、Ar2(CH2)n羰基氧、C1-4烷氧基羰基(CH2)n氧、单或二(C1-4烷基)氨基羰基、单或二(C1-4烷基)氨基羰基氧、氨基磺酰基、单或二(C1-4烷基)氨基磺酰基或选自吡咯烷基、吡咯基、二氢吡咯基、咪唑基、三唑基、哌啶基、高哌啶基、哌嗪基、吗啉基、硫代吗啉基、1-氧代-硫代吗啉基、1,1-二氧代-硫代吗啉基、吡啶基和四氢吡啶基的杂环，其中所述的每个杂环可选择性地被羰基或C1-6烷基取代；G为直接键或可选择性取代的C1-10亚烷基；R1为Ar1或单环或双环杂环；R2a和R3a中的一个是C1-6烷基，另一个是氢；如果R2a不同于氢，则R2b为氢或C1-6烷基，R3b为氢；如果R3a不同于氢，则R3b为氢或C1-6烷基，R2b为氢；t为1、2或3；Ar1为苯基或取代苯基；Ar2为苯基或取代苯基。本发明还涉及它们的制备方法和包含它们的组合物，以及它们作为药物的用途。
• Regioselective Synthesis of 2-Substituted-4-Methylbenzimidazole Nucleosides
  作者：Jiben Meng、Qi Ji、Jinliang Li、Fei Huang、Jie Han

  DOI：10.1055/s-2005-865227

  日期：——

  A series of 2-substituted-4-methylbenzimidazole nucleosides were synthesized with excellent stereo- and regioselectivity, and the unexpected regioselectivity is discussed. These compounds could be accessible on an industrial scale because they were obtained in good yields without chromatography.

  一系列2-取代-4-甲基苯并咪唑核苷被高立体选择性和区域选择性地合成，并讨论了其意外的区域选择性。这些化合物可以工业规模制备，因为它们以良好的产率获得，无需色谱分离。
• Ambident heterocyclic reactivity: Alkylation of 2-substituted-4-methylbenzimidazoles
  作者：M.Rezaul Haque、Malcolm Rasmussen

  DOI：10.1016/s0040-4020(01)80708-0

  日期：1994.5

  inducing changes in alkylation regioselectivity. The combined results are consistent with dominant ‘steric approach control’ for the alkylations, where the magnitude of the steric effect is critically dependent on the length of the developing N - - - C bond in the variable geometry SN2 alkylation transition states involved. Unequal steric effects of 2-substituents on N1 and N3 alkylations and their variation

  确定了对4-甲基-，2,4-二甲基-，2-氨基-4-甲基-，2-氯-4-甲基-，2-乙氧基-4-甲基-苯并咪唑和4-甲基的烷基化的区域选择性。甲基苯并咪唑酮（作为二甲基甲酰胺中的阴离子）与各种伯烷基化剂。在可比较的条件下，这些N 1 / N 3区域选择性与这些热杂环阴离子的苄基化的二级速率常数（苄基氯/二甲基甲酰胺/ 30°）相关。改变所述烷基化剂，[R “CH 2氯，导致沿S的松密轴移动Ñ 2过渡态的结构，并产生在区域选择性显着变化。沿晚期S N的变化由改变2- R -4-甲基苯并咪唑阴离子中的2-取代基引起的2轴在诱导烷基化区域选择性变化方面效果不佳。结合的结果与烷基化的主要“空间方法控制”相一致，其中空间效应的大小主要取决于所涉及的可变几何结构S N 2烷基化过渡态中正在发展的N--C键的长度。2-取代基对N 1和N 3烷基化的不等空间效应及其随烷基化剂的变化是通过调用氮烷基化位点的