(S)-4'-((2,3-dimethyl-5-(1-o-tolylethylcarbamoyl)-1H-indol-1-yl)methyl) biphenyl-2-carboxylic acid | 1415255-08-1

• 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: (S)-4'-((2,3-dimethyl-5-(1-o-tolylethylcarbamoyl)-1H-indol-1-yl)methyl) biphenyl-2-carboxylic acid
• 英文别名: 2-[4-[[2,3-dimethyl-5-[[(1S)-1-(2-methylphenyl)ethyl]carbamoyl]indol-1-yl]methyl]phenyl]benzoic acid
• CAS: 1415255-08-1
• 化学式: C₃₄H₃₂N₂O₃
• 分子量: 516.64
• InChiKey: HIZJHEWINJXBHY-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  71.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-((2'-(tert-butoxycarbonyl)biphenyl-4-yl)methyl)-2,3-dimethyl-1H-indole-5-carboxylic acid 在 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 1.08h， 生成 (S)-4'-((2,3-dimethyl-5-(1-o-tolylethylcarbamoyl)-1H-indol-1-yl)methyl) biphenyl-2-carboxylic acid
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Indole Biphenylcarboxylic Acids as PPARγ Antagonists

  摘要：

  The thiazolidinediones (TZD) typified by rosiglitazone are the only approved therapeutics targeting PPAR gamma for the treatment of type-2 diabetes (T2DM). Unfortunately, despite robust insulin sensitizing properties, they are accompanied by a number of severe side effects including congestive heart failure, edema, weight gain, and osteoporosis. We recently identified PPAR gamma antagonists that bind reversibly with high affinity but do not induce transactivation of the receptor, yet they act as insulin sensitizers in mouse models of diabetes (SR1664).(1) This Letter details our synthetic exploration around this novel series of PPAR gamma antagonists based on an N-biphenylmethylindole scaffold. Structure-activity relationship studies led to the identification of compound 46 as a high affinity PPAR gamma antagonist that exhibits antidiabetic properties following oral administration in diet-induced obese mice.

  DOI：

  10.1021/acsmedchemlett.5b00218

文献信息

• [EN] IMIDAZO [1,5-A]PYRIMIDINYL CARBOXAMIDE COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS<br/>[FR] COMPOSÉS IMIDAZO [1,5-A]PYRIMIDINYL CARBOXAMIDE ET LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES MÉDICAUX
  申请人：LYSOSOMAL THERAPEUTICS INC

  公开号：WO2017176961A1

  公开（公告）日：2017-10-12

  The invention provides substituted imidazo[1,5-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted imidazo[1,5-a]pyrimidinyl carboxamide compounds described herein include substituted 2-heterocyclyl-4-alkyl-imidazo[1,5-a]pyrirnidine-8-carboxamide compounds and variants thereof.

  本发明提供了取代的咪唑[1,5-a]嘧啶基甲酰胺及其相关有机化合物，包含此类化合物的组合物，医疗试剂盒，以及使用此类化合物和组合物治疗医疗障碍的方法，例如，戈谢病，帕金森病，路易体病，痴呆症或多系统萎缩症。本说明书中描述的代表性的取代咪唑[1,5-a]嘧啶基甲酰胺化合物包括取代的2-杂环基-4-烷基-咪唑[1,5-a]嘧啶-8-甲酰胺化合物及其变体。
• [EN] SUBSTITUTED IMDAZO[1,2-α]PYRIDINES, SUBSTITUTED IMIDAZO[1,2-α]PYRAZINES, RELATED COMPOUNDS, AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS<br/>[FR] IMIDAZO[1,2-A]PYRIDINES SUBSTITUÉES, IMIDAZO[1,2-A]PYRAZINES SUBSTITUÉES, COMPOSÉS APPARENTÉS ET LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES MÉDICAUX
  申请人：LYSOSOMAL THERAPEUTICS INC

  公开号：WO2017192931A1

  公开（公告）日：2017-11-09

  The invention provides substituted imidazo[1,2-α]pyridine compounds, substituted imidazo[1,2-α]pyrazine compounds, related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary imidazo[1,2-α] pyridine compounds described herein include substituted 5-methyl imidazo[1,2-α]pyridine-8-carboxamide compounds and variants thereof.

  该发明提供了替代的咪唑[1,2-α]吡啶化合物，替代的咪唑[1,2-α]吡嗪化合物，相关化合物，含有这些化合物的组合物，医疗工具包，以及使用这些化合物和组合物治疗医学疾病的方法，例如高雪氏病，帕金森病，路易体病，痴呆症，或多系统萎缩症，在患者身上。本文描述的示例咪唑[1,2-α]吡啶化合物包括替代的5-甲基咪唑[1,2-α]吡啶-8-羧酰胺化合物及其变体。
• [EN] PPARG MODULATORS FOR TREATMENT OF OSTEOPOROSIS<br/>[FR] MODULATEURS DE PPARG POUR LE TRAITEMENT DE L'OSTÉOPOROSE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2015161108A1

  公开（公告）日：2015-10-22

  The invention provides methods of treatment of a progressive bone disease, such as osteoporosis, Paget's Disease, multiple myeloma, or hyperparathyroidism, comprising administration of an effective amount of a non-agonist PPARG modulator to a patient afflicted with the disease.

  本发明提供了一种治疗进行性骨病的方法，如骨质疏松症、佩吉特病、多发性骨髓瘤或甲状旁腺功能亢进症，包括向患有该病的患者施用有效量的非激动剂PPARG调节剂。
• [EN] SUBSTITUTED IMIDAZO[1,5-A]PYRIMIDINES AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS<br/>[FR] IMIDAZO[1,5-A]PYRIMIDINES SUBSTITUÉES ET LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES MÉDICAUX
  申请人：LYSOSOMAL THERAPEUTICS INC

  公开号：WO2016073889A1

  公开（公告）日：2016-05-12

  The invention provides substituted imidazo[1,5-a]pyrimidines and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted imidazo[1,5-a]pyrimidine compounds described herein include substituted 2,4-dimethyl-N-phenylimidazo[1,5-a]pyrimidine-8-carboxamide compounds and variants thereof.

  这项发明提供了取代的咪唑并[1,5-a]嘧啶和相关的有机化合物，包含这种化合物的组合物，医疗工具包，以及使用这种化合物和组合物治疗患者的医疗疾病的方法，例如高雪氏病、帕金森病、路易体病、痴呆症或多系统萎缩症。本文描述的示例取代的咪唑并[1,5-a]嘧啶化合物包括取代的2,4-二甲基-N-苯基咪唑并[1,5-a]嘧啶-8-羧酰胺化合物及其变体。
• [EN] NON-ATP/CATALYTIC SITE p38 MITOGEN ACTIVATED PROTEIN KINASE INHIBITORS<br/>[FR] INHIBITEURS DE PROTÉINE KINASE ACTIVÉS PAR LE MITOGÈNE P38 DE SITE NON ATP/CATALYTIQUE
  申请人：UNIV MARYLAND

  公开号：WO2020118194A1

  公开（公告）日：2020-06-11

  Compounds that inhibit p38α MAPK protein, and methods of using the same, are provided for treating or preventing diseases such as cancer or inflammatory diseases.

  提供了抑制p38α MAPK蛋白的化合物，以及使用这些化合物治疗或预防癌症或炎症性疾病的方法。