[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[5-chloro-6-methyl-1-[2-(2H-triazol-4-yl)propan-2-yl]spiro[1,2-dihydroindene-3,4'-piperidine]-1'-yl]methanone | 1258596-93-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: [(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[5-chloro-6-methyl-1-[2-(2H-triazol-4-yl)propan-2-yl]spiro[1,2-dihydroindene-3,4'-piperidine]-1'-yl]methanone
• CAS: 1258596-93-8
• 化学式: C₃₄H₄₂ClF₂N₅O
• 分子量: 610.19
• InChiKey: VHZRLOCLGKGRGG-QDSWCARHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  43
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  65.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 sodium azide 作用下， 以 二甲基亚砜 为溶剂， 生成 [(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[5-chloro-6-methyl-1-[2-(2H-triazol-4-yl)propan-2-yl]spiro[1,2-dihydroindene-3,4'-piperidine]-1'-yl]methanone
  参考文献：
  名称：

  Discovery of highly potent and efficacious MC4R agonists with spiroindane N-Me-1,2,4-triazole privileged structures for the treatment of obesity

  摘要：

  We report an SAR study of MC4R analogs containing spiroindane heterocyclic privileged structures. Compound 26 with N-Me-1,2,4-triazole moiety possesses exceptional potency at MC4R and potent anti-obesity efficacy in a mouse model. However, the efficacy is not completely mediated through MC4R. Additional SAR studies led to the discovery of compound 32, which is more potent at MC4R. Compound 32 demonstrates MC4R mediated anti-obesity efficacy in rodent models. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.049

文献信息

• Discovery of highly potent and efficacious MC4R agonists with spiroindane N-Me-1,2,4-triazole privileged structures for the treatment of obesity
  作者：Shuwen He、Zhixiong Ye、Peter H. Dobbelaar、Raman K. Bakshi、Qingmei Hong、James P. Dellureficio、Iyassu K. Sebhat、Liangqin Guo、Jian Liu、Tianying Jian、Yingjie Lai、Christopher L. Franklin、Mikhail Reibarkh、Mark A. Holmes、David H. Weinberg、Tanya MacNeil、Rui Tang、Constantin Tamvakopoulos、Qianping Peng、Randy R. Miller、Ralph A. Stearns、Howard Y. Chen、Airu S. Chen、Alison M. Strack、Tung M. Fong、Matthew J. Wyvratt、Ravi P. Nargund

  DOI：10.1016/j.bmcl.2010.09.049

  日期：2010.11

  We report an SAR study of MC4R analogs containing spiroindane heterocyclic privileged structures. Compound 26 with N-Me-1,2,4-triazole moiety possesses exceptional potency at MC4R and potent anti-obesity efficacy in a mouse model. However, the efficacy is not completely mediated through MC4R. Additional SAR studies led to the discovery of compound 32, which is more potent at MC4R. Compound 32 demonstrates MC4R mediated anti-obesity efficacy in rodent models. (C) 2010 Elsevier Ltd. All rights reserved.