5-Methyl-2-trichlormethylbenzimidazol | 3584-62-1

• 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: 5-Methyl-2-trichlormethylbenzimidazol
• 英文别名: 6-methyl-2-(trichloromethyl)-1H-benzimidazole
• CAS: 3584-62-1
• 化学式: C₉H₇Cl₃N₂
• 分子量: 249.527
• InChiKey: RYVVITHBQVGCRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5-Methyl-2-trichlormethylbenzimidazol 在 水 、 sodium hydroxide 作用下， 生成 6-甲基-1H-苯并咪唑-2-羧酸
  参考文献：
  名称：

  Structure-guided design of α-amino acid-derived Pin1 inhibitors

  摘要：

  The peptidyl prolyl cis/trans isomerase Pin1 is a promising molecular target for anti-cancer therapeutics. Here we report the structure-guided evolution of an indole 2-carboxylic acid fragment hit into a series of alpha-benzimidazolyl-substituted amino acids. Examples inhibited Pin1 activity with IC50 < 100 nM, but were inactive on cells. Replacement of the benzimidazole ring with a naphthyl group resulted in a 10-50-fold loss in ligand potency, but these examples downregulated biomarkers of Pin1 activity and blocked proliferation of PC3 cells. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.090
• 作为产物：
  描述：

  N-Boc-2-(2',2',2'-trichloroacetylamino)-4-methylaniline 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以84%的产率得到5-Methyl-2-trichlormethylbenzimidazol
  参考文献：
  名称：

  Rearrangement Strategy for the Synthesis of 2-Aminoanilines

  摘要：

  Treatment of N-aryl hydroxylamines with trichloroacetonitrile in the presence of Imidazole provides a simple and effective method for the preparation of synthetically versatile 2-aminoanilines. Reactions proceed in DMF at 40 degrees C, providing the products in up to 86% isolated yield.

  DOI：

  10.1021/ol100196a

文献信息

• [EN] NITROGEN HETEROCYCLIC COMPOUNDS USEFUL AS PDE10 INHIBITORS<br/>[FR] COMPOSÉS AZOTÉS HÉTÉROCYCLIQUES CONVENANT COMME INHIBITEURS DE LA PDE10
  申请人：AMGEN INC

  公开号：WO2011143365A1

  公开（公告）日：2011-11-17

  Unsaturated nitrogen heterocyclic compounds of formula (I): (I), as defined in the specification, compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, Huntington's Disease, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

  式(I)的不饱和氮杂环化合物：(I)，如规范中定义的，含有它们的组合物，以及制备这种化合物的方法。本文还提供了通过抑制PDE10治疗可治疗的疾病或疾病的方法，如肥胖症、亨廷顿病、非胰岛素依赖型糖尿病、精神分裂症、躁郁症、强迫症等。
• Preparation and Biological Evaluation of Indole, Benzimidazole, and Thienopyrrole Piperazine Carboxamides:  Potent Human Histamine H₄ Antagonists
  作者：Jennifer D. Venable、Hui Cai、Wenying Chai、Curt A. Dvorak、Cheryl A. Grice、Jill A. Jablonowski、Chandra R. Shah、Annette K. Kwok、Kiev S. Ly、Barbara Pio、Jianmei Wei、Pragnya J. Desai、Wen Jiang、Steven Nguyen、Ping Ling、Sandy J. Wilson、Paul J. Dunford、Robin L. Thurmond、Timothy W. Lovenberg、Lars Karlsson、Nicholas I. Carruthers、James P. Edwards

  DOI：10.1021/jm0502081

  日期：2005.12.1

  lipophilic groups in the 4 and 5-positions led to increased activity in a [(3)H]histamine radiolabeled ligand competitive binding assay. In vitro metabolism and initial pharmacokinetic studies were performed on selected compounds leading to the identification of indole 8 and benzimidazole 40 as potent H(4) antagonists with the potential for further development. In addition, both 8 and 40 demonstrated

  从吲哚基-2-基-（4-甲基-哌嗪-1-基）-亚甲基衍生的三个系列的H（4）受体配体已合成，并评估了它们在H（4）上的活性构架关系竞争性结合和功能测定中的受体。在所有情况下，在[（3）H]组胺放射性标记的配体竞争性结合试验中，在4和5位上的亲脂性小基团的取代导致活性增加。对选定的化合物进行了体外代谢和初步药代动力学研究，从而导致将吲哚8和苯并咪唑40鉴定为潜在的H（4）拮抗剂，具有进一步开发的潜力。此外，8和40均在体外肥大细胞和嗜酸性粒细胞趋化性测定中显示出功效。
• Heterocyclic compounds
  申请人：——

  公开号：US20040058934A1

  公开（公告）日：2004-03-25

  Certain thienopyrrolyl and furanopyrrolyl compounds are disclosed as useful to treat or prevent disorders and conditions mediated by the histamine H 4 receptor, including allergic rhinitis.

  某些噻吩吡咯基和呋喃吡咯基化合物被揭示为治疗或预防由组胺H4受体介导的疾病和病症，包括过敏性鼻炎的有用药物。
• UNSATURATED NITROGEN HETEROCYCLIC COMPOUNDS USEFUL AS PDE10 INHIBITORS
  申请人：ALLEN Jennifer R.

  公开号：US20110306587A1

  公开（公告）日：2011-12-15

  Unsaturated nitrogen heterocyclic compounds of formula (I): as defined in the specification, compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, Huntington's Disease, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

  式(I)的不饱和氮杂环化合物，如本说明书中所定义的，含有它们的组合物以及制备这种化合物的方法。本文还提供了治疗可通过抑制PDE10治疗的疾病或疾病的方法，例如肥胖症，亨廷顿病，非胰岛素依赖性糖尿病，精神分裂症，双相情感障碍，强迫症等。
• [EN] HETEROCYCLIC COMPOUNDS<br/>[FR] COMPOSES HETEROCYCLIQUES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2004022060A2

  公开（公告）日：2004-03-18

  (1H-Benzoimidazol-2-YL)-(Piperazinyl)-Methanone derivatives of formula (I) and related compounds as histamine H4-receptor antagonists for the treatment of inflammatory and allergic disorders (I) wherein B and B1 are C or up to one of B and B1 may be N; Y is O, S or NR2, where R2 is H or C1-4alkyl; Z is O or S; R8 is H and R9 is (a), where R10 Is H or C1-4alkyl, or R8 and R9 are taken together with their N of attachment to form (b); n is 1 or 2; m is 1 or 2; n + m is 2 or 3; other substituents as defined in claim 1.

  (1H-苯并咪唑-2-基)-(哌嗪基)-甲酰胺类化合物(I)及其相关化合物，作为组胺H4受体拮抗剂用于治疗炎症性和过敏性疾病。 其中，B和B₁是C，或者B和B₁中至多一个为N；Y是O、S或NR₂，其中R₂是H或C₁₋₄烷基；Z是O或S；R₈是H，且R₉是(a)，其中R₁₀是H或C₁₋₄烷基，或者R₈和R₉与它们的连接N原子一起形成(b)；n是1或2；m是1或2；n + m是2或3；其他取代基如权利要求1所述。