[4-[(3-Chloro-4-fluorophenyl)carbamoyl-(2-pyrrolidin-1-ylethyl)amino]cyclohexen-1-yl] trifluoromethanesulfonate | 877121-65-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [4-[(3-Chloro-4-fluorophenyl)carbamoyl-(2-pyrrolidin-1-ylethyl)amino]cyclohexen-1-yl] trifluoromethanesulfonate
• CAS: 877121-65-8
• 化学式: C₂₀H₂₄ClF₄N₃O₄S
• 分子量: 513.941
• InChiKey: HVJVZSHAXYFYJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  87.3
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [4-[(3-Chloro-4-fluorophenyl)carbamoyl-(2-pyrrolidin-1-ylethyl)amino]cyclohexen-1-yl] trifluoromethanesulfonate 、 5-甲基噻酚-2-硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride sodium carbonate 、 lithium chloride 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 1.17h， 生成 3-(3-Chloro-4-fluorophenyl)-1-(4-(5-methylthiophen-2-yl)cyclohex-3-enyl)-1-(2-(pyrrolidin-1-yl)ethyl)urea
  参考文献：
  名称：

  SAR study of bicyclo[4.1.0]heptanes as melanin-concentrating hormone receptor R1 antagonists: Taming hERG

  摘要：

  To improve the ex vivo potency of MCH inhibitor la and to address its hERG liability, a structure-activity study was carried out, focusing on three regions of the lead structure. Introduction of new side chains with basic nitrogen improved in vitro and ex vivo bindings. Many potent compounds with K-i < 10 nM were discovered (compounds 6a-j) and several Compounds (14-17) had excellent ex vivo binding at 6 h and 24 h. Attenuating the basicity of nitrogen on the side chain, and in particular, introduction of a polar group such as aminomethyl on the distal phenyl ring significantly lowered the hERG activity. Further replacement of the distal phenyl group with heteroaryl groups in the cyclohexene series provided compounds such as 281 with excellent ex vivo activity with much reduced hERG liability. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.05.068
• 作为产物：
  描述：

  [4-(2-Pyrrolidin-1-ylethylamino)cyclohexen-1-yl] trifluoromethanesulfonate 、 异氰酸- 3-氯-4-氟苯酯 以 二氯甲烷 为溶剂， 反应 3.0h， 以96%的产率得到[4-[(3-Chloro-4-fluorophenyl)carbamoyl-(2-pyrrolidin-1-ylethyl)amino]cyclohexen-1-yl] trifluoromethanesulfonate
  参考文献：
  名称：

  SAR study of bicyclo[4.1.0]heptanes as melanin-concentrating hormone receptor R1 antagonists: Taming hERG

  摘要：

  To improve the ex vivo potency of MCH inhibitor la and to address its hERG liability, a structure-activity study was carried out, focusing on three regions of the lead structure. Introduction of new side chains with basic nitrogen improved in vitro and ex vivo bindings. Many potent compounds with K-i < 10 nM were discovered (compounds 6a-j) and several Compounds (14-17) had excellent ex vivo binding at 6 h and 24 h. Attenuating the basicity of nitrogen on the side chain, and in particular, introduction of a polar group such as aminomethyl on the distal phenyl ring significantly lowered the hERG activity. Further replacement of the distal phenyl group with heteroaryl groups in the cyclohexene series provided compounds such as 281 with excellent ex vivo activity with much reduced hERG liability. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.05.068

文献信息

• [EN] HETEROCYCLYLS AS SELECTIVE MELANIN CONCENTRATING HORMONE RECEPTOR ANTAGONISTS FOR THE TREATMENT OF OBESITY AND RELATED DISORDERS<br/>[FR] NOUVEAUX HETEROCYCLYLES UTILISES EN TANT QU'ANTAGONISTES DU RECEPTEUR DE L'HORMONE CONCENTRANT LA MELANINE POUR LE TRAITEMENT DE L'OBESITE ET DE TROUBLES ASSOCIES
  申请人：SCHERING CORP

  公开号：WO2006019957A3

  公开（公告）日：2006-04-27
• US7361769B2
  申请人：——

  公开号：US7361769B2

  公开（公告）日：2008-04-22
• SAR study of bicyclo[4.1.0]heptanes as melanin-concentrating hormone receptor R1 antagonists: Taming hERG
  作者：Jing Su、Brian A. McKittrick、Haiqun Tang、Duane A. Burnett、John W. Clader、William J. Greenlee、Brian E. Hawes、Kim O’Neill、Brian Spar、Blair Weig、Timothy Kowalski、Steve Sorota、Cheng Li、Tongtong Liu

  DOI：10.1016/j.bmc.2007.05.068

  日期：2007.8

  To improve the ex vivo potency of MCH inhibitor la and to address its hERG liability, a structure-activity study was carried out, focusing on three regions of the lead structure. Introduction of new side chains with basic nitrogen improved in vitro and ex vivo bindings. Many potent compounds with K-i < 10 nM were discovered (compounds 6a-j) and several Compounds (14-17) had excellent ex vivo binding at 6 h and 24 h. Attenuating the basicity of nitrogen on the side chain, and in particular, introduction of a polar group such as aminomethyl on the distal phenyl ring significantly lowered the hERG activity. Further replacement of the distal phenyl group with heteroaryl groups in the cyclohexene series provided compounds such as 281 with excellent ex vivo activity with much reduced hERG liability. (c) 2007 Elsevier Ltd. All rights reserved.