ethyl 2-(1-benzyl-1H-benzo[d]imidazol-2-ylthio)acetate | 400742-86-1

• 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: ethyl 2-(1-benzyl-1H-benzo[d]imidazol-2-ylthio)acetate
• 英文别名: ethyl [(1-benzyl-1H-benzimidazol-2-yl)sulfanyl]acetate；ethyl 2-(1-benzylbenzimidazol-2-yl)sulfanylacetate
• CAS: 400742-86-1
• 化学式: C₁₈H₁₈N₂O₂S
• mdl: MFCD01136170
• 分子量: 326.419
• InChiKey: HGEWJVGTMUCUCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  69.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-(1-benzyl-1H-benzo[d]imidazol-2-ylthio)acetate 在 溶剂黄146 一水合肼 作用下， 以 乙醇 为溶剂， 反应 32.0h， 生成 (E)-2-(1-benzyl-1H-benzo[d]imidazol-2-ylthio)-N'-(4-ethoxy-3-methoxybenzylidene)acetohydrazide
  参考文献：
  名称：

  [EN] PDE10 INHIBITORS AND RELATED COMPOSITIONS AND METHODS
  [FR] INHIBITEURS DE LA PDE10 ET COMPOSITIONS ET PROCÉDÉS ASSOCIÉS

  摘要：

  公开号：

  WO2009143178A3
• 作为产物：
  描述：

  benzimidazole-2-thione 在 sodium hydride 、 potassium carbonate 作用下， 以 乙醚 、 乙醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 16.33h， 生成 ethyl 2-(1-benzyl-1H-benzo[d]imidazol-2-ylthio)acetate
  参考文献：
  名称：

  [EN] PDE10 INHIBITORS AND RELATED COMPOSITIONS AND METHODS
  [FR] INHIBITEURS DE LA PDE10 ET COMPOSITIONS ET PROCÉDÉS ASSOCIÉS

  摘要：

  公开号：

  WO2009143178A3

文献信息

• PDE10 INHIBITORS AND RELATED COMPOSITIONS AND METHODS
  申请人：Bergmann John E.

  公开号：US20080300240A1

  公开（公告）日：2008-12-04

  Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. The compounds have the general structure: wherein m, n, p, x, R, R 1 , R 2 , R 3 , R 4 , R 5 , A and B, are defined herein, including pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE 10 in a warm-blooded animal in need of the same.

  抑制PDE10的化合物已被披露，对治疗包括（但不限于）精神病、焦虑、运动障碍和/或神经系统疾病（如帕金森病、亨廷顿病、阿尔茨海默病、脑炎、恐惧症、癫痫、失语症、贝尔氏面瘫、脑瘫、睡眠障碍、疼痛、抽动症、精神分裂症、妄想症、药物诱发的精神病和恐慌以及强迫症）多种疾病具有用途。这些化合物具有一般结构： 其中m、n、p、x、R、R1、R2、R3、R4、R5、A和B在此定义，包括药学上可接受的盐、立体异构体、溶剂合物或其前药。还披露了含有本发明化合物的组合物，与药学上可接受的载体结合，以及与使用这些化合物抑制需要同样的PDE10的温血动物相关的方法。
• PDE10 inhibitors and related compositions and methods
  申请人：Omeros Corporation

  公开号：US08278327B2

  公开（公告）日：2012-10-02

  Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. The compounds have the general structure: wherein m, n, p, x, R, R1, R2, R3, R4, R5, A and B, are defined herein, including pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.

  本发明公开了抑制PDE10的化合物，其在治疗各种疾病方面具有用途，包括（但不限于）精神病、焦虑、运动障碍和/或神经系统疾病，如帕金森病、亨廷顿病、阿尔茨海默病、脑炎、恐惧症、癫痫、失语症、贝尔麻痹症、脑瘫、睡眠障碍、疼痛、抽动症、精神分裂症、妄想性障碍、药物诱导的精神病和惊恐和强迫症。该化合物具有以下一般结构：其中m、n、p、x、R、R1、R2、R3、R4、R5、A和B在此定义，包括其药学上可接受的盐、立体异构体、溶剂化物或前药。本发明还公开了含有本发明化合物及其药学上可接受的载体的组合物，以及与之相关的方法，用于在需要的恒温动物中抑制PDE10。
• Novel histone deacetylase 6 inhibitors using benzimidazole as caps for cancer treatment
  作者：Phuong Hong Nguyen、Bui Thi Buu Hue、Minh Quan Pham、Tran Phuong Hoa、Quang De Tran、Hosun Jung、Le Trong Hieu、Nguyen Cuong Quoc、Hong Vinh Quang、Nguyen Phu Quy、Hye Jin Yoo、Su-Geun Yang

  DOI：10.1039/d2nj05731j

  日期：——

  exhibited antiproliferative effects against a panel of cancer cell lines. Compound 7 was the most potent selective inhibitor of HDAC6 and had an IC50 value 8- to >111.1-fold those of HDAC3, HDAC4, HDAC8, and HDAC11, and was a superior HDAC6 inhibitor to belinostat. Its interaction with and inhibitory activity on HDAC enzymes were then explored in a molecular docking study. The obtained data revealed the highest

  组蛋白脱乙酰酶 (HDAC) 已被证明是开发抗癌药物的有前途的目标。在这项工作中，我们报告了一系列与苯并咪唑和苯并恶唑核心结构缀合的 19 种新型异羟肟酸基组蛋白脱乙酰酶抑制剂的设计和合成。五种化合物显示出抗增殖活性，IC 50值为 2.9–70.9 μM。化合物7显示出对 MCF-7 细胞的最高功效，并显示出对一组癌细胞系的抗增殖作用。化合物7是最有效的 HDAC6 选择性抑制剂，具有 IC 50值是 HDAC3、HDAC4、HDAC8 和 HDAC11 的 8 到 >111.1 倍，并且是优于 belinostat 的 HDAC6 抑制剂。然后在分子对接研究中探索了它与 HDAC 酶的相互作用和抑制活性。获得的数据揭示了化合物7对 HDAC6的最高结合亲和力 (-8.46 kcal mol -1 ) ，因为它与活性位点内的关键残基 Cys584 和 Asp612 形成相互作用。此外，化合物7的
• Structure-based design generated novel hydroxamic acid based preferential HDAC6 lead inhibitor with on-target cytotoxic activity against primary choroid plexus carcinoma
  作者：Shaymaa E. Kassab、Samar Mowafy、Aya M. Alserw、Joustin A. Seliem、Shahenda M. El-Naggar、Nesreen N. Omar、Mohamed M. Awad

  DOI：10.1080/14756366.2019.1613987

  日期：2019.1.1

  Histone deacetylase 6 (HDAC6) is an attractive target for cancer therapeutic intervention. Selective HDAC6 inhibitors is important to minimise the side effects of pan inhibition. Thus, new class of hydroxamic acid-based derivatives were designed on structural basis to perform preferential activity against HDAC6 targeting solid tumours. Interestingly, 1-benzylbenzimidazole-2-thio-N-hydroxybutanamide 10a showed impressive preference with submicromolar potency against HDAC6 (IC50 = 510 nM). 10a showed cytotoxic activity with interesting profile against CCHE-45 at (IC50 = 112.76 mu M) when compared to standard inhibitor Tubacin (IC50 = 20 mu M). Western blot analysis of acetylated-alpha-tubulin verified the HDAC6 inhibiting activity of 10a. Moreover, the insignificant difference in acetylated-alpha-tubulin induced by 10a and Tubacin implied the on-target cytotoxic activity of 10a. Docking of 10a in the binding site of HDAC6 attributed the activity of 10a to pi-pi stacking with the amino acids of the hydrophobic channel of HDAC6 and capture of zinc metal in bidentate fashion. The therapeutic usefulness besides the on-target activity may define 10a as an interesting safe-lead inhibitor for future development.[GRAPHICS].
• US7786139B2
  申请人：——

  公开号：US7786139B2

  公开（公告）日：2010-08-31