7-(n-propyloxy)-1-(3,4-dichlorobenzyl)-1H-benzo[d]imidazole-2-amine | 1276029-11-8

• 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: 7-(n-propyloxy)-1-(3,4-dichlorobenzyl)-1H-benzo[d]imidazole-2-amine
• 英文别名: 2-Aminobenzimidazole deriv., 11；1-[(3,4-dichlorophenyl)methyl]-7-propoxybenzimidazol-2-amine
• CAS: 1276029-11-8
• 化学式: C₁₇H₁₇Cl₂N₃O
• 分子量: 350.247
• InChiKey: ODCTYJXVCFVIBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  53.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  7-(n-propyloxy)-1H-benzo[d]imidazole-2-amine 、 3,4-二氯氯苄 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 48.0h， 以20%的产率得到7-(n-propyloxy)-1-(3,4-dichlorobenzyl)-1H-benzo[d]imidazole-2-amine
  参考文献：
  名称：

  One Scaffold, Three Binding Modes: Novel and Selective Pteridine Reductase 1 Inhibitors Derived from Fragment Hits Discovered by Virtual Screening

  摘要：

  The enzyme pteridine reductase 1 (PTR1) is a potential target for new compounds to treat human African trypanosomiasis. A virtual screening campaign for fragments inhibiting PTR1 was carried out. Two novel chemical series were identified containing aminobenzothiazole and aminobenzimidazole scaffolds, respectively. One of the hits (2-amino-6-chloro-benzimidazole) was subjected to crystal structure analysis and a high resolution crystal structure in complex with PTR1 was obtained, confirming the predicted binding mode. However, the crystal structures of two analogues (2-amino-benzimidazole and 1-(3,4-dichloro-benzyl)-2-amino-benzimidazole) in complex with PTR1 revealed two alternative binding modes. In these complexes, previously unobserved protein movements and water-mediated protein-ligand contacts occurred, which prohibited a correct prediction of the binding modes. On the basis of the alternative binding mode of 1-(3,4-dichloro-benzyl)-2-amino-benzimidazole, derivatives were designed and selective PTR1 inhibitors with low nanomolar potency and favorable physicochemical properties were obtained.

  DOI：

  10.1021/jm900414x

文献信息

• One Scaffold, Three Binding Modes: Novel and Selective Pteridine Reductase 1 Inhibitors Derived from Fragment Hits Discovered by Virtual Screening
  作者：Chidochangu P. Mpamhanga、Daniel Spinks、Lindsay B. Tulloch、Emma J. Shanks、David A. Robinson、Iain T. Collie、Alan H. Fairlamb、Paul G. Wyatt、Julie A. Frearson、William N. Hunter、Ian H. Gilbert、Ruth Brenk

  DOI：10.1021/jm900414x

  日期：2009.7.23

  The enzyme pteridine reductase 1 (PTR1) is a potential target for new compounds to treat human African trypanosomiasis. A virtual screening campaign for fragments inhibiting PTR1 was carried out. Two novel chemical series were identified containing aminobenzothiazole and aminobenzimidazole scaffolds, respectively. One of the hits (2-amino-6-chloro-benzimidazole) was subjected to crystal structure analysis and a high resolution crystal structure in complex with PTR1 was obtained, confirming the predicted binding mode. However, the crystal structures of two analogues (2-amino-benzimidazole and 1-(3,4-dichloro-benzyl)-2-amino-benzimidazole) in complex with PTR1 revealed two alternative binding modes. In these complexes, previously unobserved protein movements and water-mediated protein-ligand contacts occurred, which prohibited a correct prediction of the binding modes. On the basis of the alternative binding mode of 1-(3,4-dichloro-benzyl)-2-amino-benzimidazole, derivatives were designed and selective PTR1 inhibitors with low nanomolar potency and favorable physicochemical properties were obtained.