(R)-1-(4-chlorobenzyl)-N-(1-phenylpropyl)-1H-benzo[d]imidazole-5-carboxamide | 1168138-00-8

• 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: (R)-1-(4-chlorobenzyl)-N-(1-phenylpropyl)-1H-benzo[d]imidazole-5-carboxamide
• 英文别名: 1-[(4-chlorophenyl)methyl]-N-[(1R)-1-phenylpropyl]-1H-benzimidazole-5-carboxamide；1-[(4-chlorophenyl)methyl]-N-[(1R)-1-phenylpropyl]benzimidazole-5-carboxamide
• CAS: 1168138-00-8
• 化学式: C₂₄H₂₂ClN₃O
• 分子量: 403.911
• InChiKey: WMNPOHVYNADEHY-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  46.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (R)-(+)-1-苯丙胺 在 tin(II) chloride dihdyrate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 41.0h， 生成 (R)-1-(4-chlorobenzyl)-N-(1-phenylpropyl)-1H-benzo[d]imidazole-5-carboxamide
  参考文献：
  名称：

  Discovery of GSK1997132B a novel centrally penetrant benzimidazole PPARγ partial agonist

  摘要：

  The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-activated nuclear receptor, thought to play a role in energy metabolism, glucose homeostasis and microglia-mediated neuroinflammation. A novel benzimidazole series of centrally penetrant PPAR gamma partial agonists has been identified. The optimization of PPAR gamma activity and in vivo pharmacokinetics leading to the identification of GSK1997132B a potent, metabolically stable and centrally penetrant PPAR gamma partial agonist, is described. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.088

文献信息

• N-BENZYLBENZIMIDAZOLE MODULATORS OF PPARG
  申请人：Kamenecka Theodore Mark

  公开号：US20140249196A1

  公开（公告）日：2014-09-04

  The invention provides molecular entities that bind with high affinity to PPARG (PPARγ), inhibit cdk5-mediated phosphorylation of PPARG, but do not exert an agonistic effect on PPARG. Compounds of the invention can be used for treatment of conditions in patients wherein PPARG plays a role, such as diabetes or obesity. Methods of preparation of the compounds, bioassay methods for evaluating compounds of the invention as non-agonistic PPARG binding compounds, and pharmaceutical compositions are also provided.

  本发明提供了与PPARG（PPARγ）高亲和力结合、抑制cdk5介导的PPARG磷酸化，但不对PPARG产生激动作用的分子实体。本发明的化合物可用于治疗PPARG在糖尿病或肥胖等病患中发挥作用的情况。本发明还提供了化合物的制备方法、评估本发明的化合物作为非激动性PPARG结合化合物的生物测定方法和制药组合物。
• Discovery of GSK1997132B a novel centrally penetrant benzimidazole PPARγ partial agonist
  作者：Mairi Sime、Amanda C. Allan、Paul Chapman、Charlotte Fieldhouse、Gerard M.P. Giblin、Mark P. Healy、Millard H. Lambert、Lisa M. Leesnitzer、Ann Lewis、Raymond V. Merrihew、Richard A. Rutter、Rosemary Sasse、Barry G. Shearer、Timothy M. Wilson、Robert X. Xu、David J. Virley

  DOI：10.1016/j.bmcl.2011.06.088

  日期：2011.9

  The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-activated nuclear receptor, thought to play a role in energy metabolism, glucose homeostasis and microglia-mediated neuroinflammation. A novel benzimidazole series of centrally penetrant PPAR gamma partial agonists has been identified. The optimization of PPAR gamma activity and in vivo pharmacokinetics leading to the identification of GSK1997132B a potent, metabolically stable and centrally penetrant PPAR gamma partial agonist, is described. (C) 2011 Elsevier Ltd. All rights reserved.