tert-butyl 4'-((2-methyl-5-((1-phenylpropyl)carbamoyl)-1H-indol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylate | 1415257-25-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: tert-butyl 4'-((2-methyl-5-((1-phenylpropyl)carbamoyl)-1H-indol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylate
• 英文别名: tert-Butyl 4'-((2-methyl-5-((1-phenylpropyl)carbamoyl)-1H-indol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylate；tert-butyl 2-[4-[[2-methyl-5-(1-phenylpropylcarbamoyl)indol-1-yl]methyl]phenyl]benzoate
• CAS: 1415257-25-8
• 化学式: C₃₇H₃₈N₂O₃
• 分子量: 558.72
• InChiKey: LODHKWFLUXKQET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  60.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4'-((2-methyl-5-((1-phenylpropyl)carbamoyl)-1H-indol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 4'-((2-methyl-5-((1-phenylpropyl)carbamoyl)-1H-indol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylic acid
  参考文献：
  名称：

  Synthesis and biological activities of novel indole derivatives as potent and selective PPARγ modulators

  摘要：

  Starting from the structure of Telmisartan, a new series of potent and selective PPAR gamma modulators was identified. The synthesis, in vitro and in vivo evaluation of the most potent compounds are reported and the X-ray structure of compound 7b bound to the PPAR gamma ligand binding domain is described. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.107
• 作为产物：
  描述：

  1-((2'-(tert-butoxycarbonyl)-[1,1'-biphenyl]-4-yl)methyl)-2-methyl-1H-indole-5-carboxylic acid 、 1-苯基丙-1-胺 生成 tert-butyl 4'-((2-methyl-5-((1-phenylpropyl)carbamoyl)-1H-indol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylate
  参考文献：
  名称：

  N-BIPHENYLMETHYLINDOLE MODULATORS OF PPARG

  摘要：

  本发明提供了与PPARG（PPARγ）高亲和力结合、抑制激酶介导的，例如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在患者中发挥作用的疾病，例如糖尿病、胰岛素抵抗、糖耐量受损、糖尿病前期、高血糖、高胰岛素血症、肥胖或炎症。在使用本发明的化合物进行这些疾病的治疗方法中，该化合物可避免在接受化合物的患者中产生显著体重增加、水肿、骨生长或形成障碍或心脏肥大等副作用，或任何组合。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以及制药组合物。

  公开号：

  US20120309757A1

文献信息

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

  公开号：US20120309757A1

  公开（公告）日：2012-12-06

  The invention provides molecular entities that bind with high affinity to PPARG (PPARγ), inhibit kinase-mediated, e.g., 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, insulin resistance, impaired glucose tolerance, pre-diabetes, hyperglycemia, hyperinsulinemia, obesity, or inflammation. In methods of treatment of these conditions using a compound of the invention, the compound can avoid producing side effects of significant weight gain, edema, impairment of bone growth or formation, or cardiac hypertrophy, or any combination thereof, in the patient receiving the compound. 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、抑制激酶介导的，例如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在患者中发挥作用的疾病，例如糖尿病、胰岛素抵抗、糖耐量受损、糖尿病前期、高血糖、高胰岛素血症、肥胖或炎症。在使用本发明的化合物进行这些疾病的治疗方法中，该化合物可避免在接受化合物的患者中产生显著体重增加、水肿、骨生长或形成障碍或心脏肥大等副作用，或任何组合。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以及制药组合物。
• N-biphenylmethylindole modulators of PPARG
  申请人：Kamenecka Theodore Mark

  公开号：US08957093B2

  公开（公告）日：2015-02-17

  The invention provides molecular entities that bind with high affinity to PPARG (PPARγ), inhibit kinase-mediated, e.g., 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, insulin resistance, impaired glucose tolerance, pre-diabetes, hyperglycemia, hyperinsulinemia, obesity, or inflammation. In methods of treatment of these conditions using a compound of the invention, the compound can avoid producing side effects of significant weight gain, edema, impairment of bone growth or formation, or cardiac hypertrophy, or any combination thereof, in the patient receiving the compound. 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、抑制激酶介导的（例如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患有PPARG参与的疾病的患者，如糖尿病、胰岛素抵抗、糖耐量受损、糖尿病前期、高血糖、高胰岛素血症、肥胖或炎症。在使用本发明的化合物进行这些疾病的治疗方法中，该化合物可以避免在接受该化合物的患者中产生显著的体重增加、水肿、骨生长或形成的损伤、心脏肥大或任何组合的副作用。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以及制药组合物。
• Synthesis and biological activities of novel indole derivatives as potent and selective PPARγ modulators
  作者：Yann Lamotte、Paul Martres、Nicolas Faucher、Alain Laroze、Didier Grillot、Nicolas Ancellin、Yannick Saintillan、Véronique Beneton、Robert T. Gampe

  DOI：10.1016/j.bmcl.2009.12.107

  日期：2010.2

  Starting from the structure of Telmisartan, a new series of potent and selective PPAR gamma modulators was identified. The synthesis, in vitro and in vivo evaluation of the most potent compounds are reported and the X-ray structure of compound 7b bound to the PPAR gamma ligand binding domain is described. (C) 2010 Elsevier Ltd. All rights reserved.