6-tert-butyl-2-[4-(3-chloropyridin-2-yl)piperazin-1-yl]-1H-benzoimidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 6-tert-butyl-2-[4-(3-chloropyridin-2-yl)piperazin-1-yl]-1H-benzoimidazole
• 英文别名: 6-tert-Butyl-2-[4-(3-chloro-pyridin-2-yl)-piperazin-1-yl]-1H-benzoimidazole；6-tert-butyl-2-[4-(3-chloropyridin-2-yl)piperazin-1-yl]-1H-benzimidazole
• 化学式: C₂₀H₂₄ClN₅
• 分子量: 369.897
• InChiKey: HLFPSEKSWJSPOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  48
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,3-二氯吡啶 在 N,N-二异丙基乙胺 作用下， 以 对二甲苯 、 乙腈 为溶剂， 生成 6-tert-butyl-2-[4-(3-chloropyridin-2-yl)piperazin-1-yl]-1H-benzoimidazole
  参考文献：
  名称：

  4-(2-Pyridyl)piperazine-1-benzimidazoles as potent TRPV1 antagonists

  摘要：

  A series of 4-(2-pyridyl)piperazine-1-benzimidazole analogues based on compound I was synthesized and evaluated for TRPV1 antagonist activity in capsaicin-induced (CAP) and pH5.5-induced (pH) FLIPR assays in a human TRPV1 -expressing HEK293 cell line. Potent TRPV1 antagonists were identified through SAR studies. From these studies, several antagonists were found, with IC50 values ranging from 32nM to similar to5000nM. Among these, 11 [IC50 = 90nM (CAP) and 104nM (pH)] was further evaluated and found to be orally available in rats (F% = 19.7). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.11.021

文献信息

• VANILLOID RECEPTOR LIGANDS AND THEIR USE IN TREATMENTS
  申请人：Balan Chenera

  公开号：US20090143575A1

  公开（公告）日：2009-06-04

  Therapeutic benzimidazoles and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotizing agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

  治疗苯并咪唑及其含量物，用于急性、炎症性和神经痛、牙痛、一般头痛、偏头痛、集群性头痛、混合血管和非血管综合症、紧张型头痛、一般炎症、关节炎、风湿性疾病、骨关节炎、炎症性肠病、炎症性眼病、炎症性或不稳定的膀胱疾病、牛皮癣、有炎症成分的皮肤病、慢性炎症状况、炎症性疼痛和相关的高敏感性和触痛、神经痛和相关的高敏感性和触痛、糖尿病神经病疼痛、烧伤后疼痛、交感神经维持的疼痛、去感觉综合症、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸、泌尿、胃肠或血管区域内脏运动障碍、伤口、烧伤、过敏性皮肤反应、瘙痒、白癜风、一般胃肠疾病、胃溃疡、十二指肠溃疡、腹泻、坏死性剂引起的胃损伤、头发生长、血管运动或过敏性鼻炎、支气管疾病或膀胱疾病。
• 4-(2-Pyridyl)piperazine-1-benzimidazoles as potent TRPV1 antagonists
  作者：Bin Shao、Jincheng Huang、Qun Sun、Kenneth J. Valenzano、Lori Schmid、Scott Nolan

  DOI：10.1016/j.bmcl.2004.11.021

  日期：2005.2

  A series of 4-(2-pyridyl)piperazine-1-benzimidazole analogues based on compound I was synthesized and evaluated for TRPV1 antagonist activity in capsaicin-induced (CAP) and pH5.5-induced (pH) FLIPR assays in a human TRPV1 -expressing HEK293 cell line. Potent TRPV1 antagonists were identified through SAR studies. From these studies, several antagonists were found, with IC50 values ranging from 32nM to similar to5000nM. Among these, 11 [IC50 = 90nM (CAP) and 104nM (pH)] was further evaluated and found to be orally available in rats (F% = 19.7). (C) 2004 Elsevier Ltd. All rights reserved.
• US7582761B2
  申请人：——

  公开号：US7582761B2

  公开（公告）日：2009-09-01
• US8026241B2
  申请人：——

  公开号：US8026241B2

  公开（公告）日：2011-09-27
• Design of Potent, Orally Available Antagonists of the Transient Receptor Potential Vanilloid 1. Structure−Activity Relationships of 2-Piperazin-1-yl-1<i>H</i>-benzimidazoles
  作者：Vassil I. Ognyanov、Chenera Balan、Anthony W. Bannon、Yunxin Bo、Celia Dominguez、Christopher Fotsch、Vijay K. Gore、Lana Klionsky、Vu V. Ma、Yi-Xin Qian、Rami Tamir、Xianghong Wang、Ning Xi、Shimin Xu、Dawn Zhu、Narender R. Gavva、James J. S. Treanor、Mark H. Norman

  DOI：10.1021/jm060065y

  日期：2006.6.1

  The vanilloid receptor-1 ( VR1 or TRPV1) is a membrane-bound, nonselective cation channel that is predominantly expressed by peripheral neurons sensing painful stimuli. TRPV1 antagonists produce antihyperalgesic effects in animal models of inflammatory and neuropathic pain. Herein, we describe the synthesis and the structure-activity relationships of a series of 2-(4-pyridin-2-ylpiperazin-1-yl)-1H-benzo-[ d] imidazoles as novel TRPV1 antagonists. Compound 46ad was among the most potent analogues in this series. This compound was orally bioavailable in rats and was efficacious in blocking capsaicin-induced flinch in rats in a dose-dependent manner. Compound 46ad also reversed thermal hyperalgesia in a model of inflammatory pain, which was induced by complete Freund's adjuvant ( CFA).