ethyl 4-[1,3-dihydro-2-oxo-5-(trifluoromethyl)-2H-benzimidazol-1-yl]-1-piperidinecarboxylate | 58859-49-7

• 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 4-[1,3-dihydro-2-oxo-5-(trifluoromethyl)-2H-benzimidazol-1-yl]-1-piperidinecarboxylate
• 英文别名: ethyl 4-[2-oxo-5-(trifluoromethyl)-3H-benzimidazol-1-yl]piperidine-1-carboxylate
• CAS: 58859-49-7
• 化学式: C₁₆H₁₈F₃N₃O₃
• 分子量: 357.332
• InChiKey: OXCKJKTVPZPIBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 4-[1,3-dihydro-2-oxo-5-(trifluoromethyl)-2H-benzimidazol-1-yl]-1-piperidinecarboxylate 在 sodium hydroxide 作用下， 生成 1-(piperidin-4-yl)-5-(trifluoromethyl)-1H-benzo[d]imidazole-2(3H)-one
  参考文献：
  名称：

  Benzodiazepine calcitonin gene-related peptide (CGRP) receptor antagonists: Optimization of the 4-substituted piperidine

  摘要：

  In our continuing effort to identify CGRP receptor antagonists for the acute treatment of migraine, we have undertaken a study to evaluate alternative 4-substituted piperidines to the lead dihydroquinazolinone 1. In this regard, we have identified the piperidinyl-azabenzimidazolone and phenylimidazolinone structures which, when incorporated into the benzodiazepine core, afford potent CGRP receptor antagonists (e.g., 18 and 29). These studies produced a potent analog (18) which overcomes the instability issues associated with the lead structure 1. A general pharmacophore for the 4-substituted piperidine component of these CGRP receptor antagonists is also presented. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.044
• 作为产物：
  描述：

  ethyl 4-[2-amino-4-(trifluoromethyl)phenylamino]-1-piperidinecarboxylate 在 尿素 作用下， 生成 ethyl 4-[1,3-dihydro-2-oxo-5-(trifluoromethyl)-2H-benzimidazol-1-yl]-1-piperidinecarboxylate
  参考文献：
  名称：

  Benzimidazolinone derivatives

  摘要：

  新型苯并咪唑啉酮衍生物及其治疗上可接受的酸盐，这些化合物可用作长效抗精神病药物。

  公开号：

  US03989707A1

文献信息

• Synthesis and neuroleptic activity of a series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimidazolone derivatives
  作者：Rainer Henning、Rudolf Lattrell、Hermann J. Gerhards、Margret Leven

  DOI：10.1021/jm00388a012

  日期：1987.5

  A series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimid azolones with various substituents in both aromatic rings have been synthesized and tested for neuroleptic activity (antiapomorphine effects and [3H]spiroperidol binding) as well as extrapyramidal effects (cataleptogenic effect). A strong dependence of activity on the 5-substituent in the benzimidazolone moiety could be demonstrated. Some compounds show a large split between the desired antiapomorphine and the undesired extrapyramidal effect. From these, 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]-5-chlor obenzimidazol-2-one hydrochloride (HR 723), 12, has been selected for further preclinical and toxicological profiling.
• HENNING R.; LATTRELL R.; GARHARDS H. J.; LEVEN M., J. MED. CHEM., 30,(1987) N 5, 814-819
  作者：HENNING R.、 LATTRELL R.、 GARHARDS H. J.、 LEVEN M.

  DOI：——

  日期：——
• US3989707A
  申请人：——

  公开号：US3989707A

  公开（公告）日：1976-11-02
• Benzimidazolinone derivatives
  申请人：Janssen Pharmaceutica N.V.

  公开号：US03989707A1

  公开（公告）日：1976-11-02

  Novel benzimidazolinone derivatives and therapeutically acceptable acid addition salts thereof, said compounds being useful as long acting neuroleptic agents.

  新型苯并咪唑啉酮衍生物及其治疗上可接受的酸盐，这些化合物可用作长效抗精神病药物。
• Benzodiazepine calcitonin gene-related peptide (CGRP) receptor antagonists: Optimization of the 4-substituted piperidine
  作者：Christopher S. Burgey、Craig A. Stump、Diem N. Nguyen、James Z. Deng、Amy G. Quigley、Beth R. Norton、Ian M. Bell、Scott D. Mosser、Christopher A. Salvatore、Ruth Z. Rutledge、Stefanie A. Kane、Kenneth S. Koblan、Joseph P. Vacca、Samuel L. Graham、Theresa M. Williams

  DOI：10.1016/j.bmcl.2006.07.044

  日期：2006.10

  In our continuing effort to identify CGRP receptor antagonists for the acute treatment of migraine, we have undertaken a study to evaluate alternative 4-substituted piperidines to the lead dihydroquinazolinone 1. In this regard, we have identified the piperidinyl-azabenzimidazolone and phenylimidazolinone structures which, when incorporated into the benzodiazepine core, afford potent CGRP receptor antagonists (e.g., 18 and 29). These studies produced a potent analog (18) which overcomes the instability issues associated with the lead structure 1. A general pharmacophore for the 4-substituted piperidine component of these CGRP receptor antagonists is also presented. (c) 2006 Elsevier Ltd. All rights reserved.