Tert-butyl 6-[[[1-[2-(3,5-dimethylphenyl)acetyl]-2-methylazetidine-2-carbonyl]-(4-ethoxy-4-oxobutyl)amino]methyl]indole-1-carboxylate | 1391079-07-4

• 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 6-[[[1-[2-(3,5-dimethylphenyl)acetyl]-2-methylazetidine-2-carbonyl]-(4-ethoxy-4-oxobutyl)amino]methyl]indole-1-carboxylate
• CAS: 1391079-07-4
• 化学式: C₃₅H₄₅N₃O₆
• 分子量: 603.759
• InChiKey: GPMVETXRYDFDSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  98.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Tert-butyl 6-[[[1-[2-(3,5-dimethylphenyl)acetyl]-2-methylazetidine-2-carbonyl]-(4-ethoxy-4-oxobutyl)amino]methyl]indole-1-carboxylate 在 sodium hydroxide 、 柠檬酸 作用下， 以 水 为溶剂， 生成 4-[[1-(2-benzofuran-3-ylacetyl)-2-methylazetidine-2-carbonyl](1H-indol-6-ylmethyl)amino]butyric acid
  参考文献：
  名称：

  Discovery and Optimization of an Azetidine Chemical Series As a Free Fatty Acid Receptor 2 (FFA2) Antagonist: From Hit to Clinic

  摘要：

  FFA2, also called GPR43, is a G-protein coupled receptor for short chain fatty acids which is involved in the mediation of inflammatory responses. A class of azetidines was developed as potent FFA2 antagonists. Multiparametric optimization of early hits with moderate potency and suboptimal ADME properties led to the identification of several compounds with nanomolar potency on the receptor combined with excellent pharmacokinetic (PK) parameters. The most advanced compound, 4-[[(R)-1-(benzo[b]thiophene-3-carbonyl)-2-methyl-azetidine-2-carbonyl]-(3-chloro-benzyl)-amino]-butyric acid 99 (GLPG0974), is able to inhibit acetate-induced neutrophil migration strongly in vitro and demonstrated ability to inhibit a neutrophil-based pharmacodynamic (PD) marker, CD11b activation-specific epitope [AE], in a human whole blood assay. All together, these data supported the progression of 99 toward next phases, becoming the first FFA2 antagonist to reach the clinic.

  DOI：

  10.1021/jm5012885
• 作为产物：
  描述：

  1-[2-(3,5-dimethylphenyl)acetyl]-2-methylazetidine-2-carboxylic acid 在 草酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 Tert-butyl 6-[[[1-[2-(3,5-dimethylphenyl)acetyl]-2-methylazetidine-2-carbonyl]-(4-ethoxy-4-oxobutyl)amino]methyl]indole-1-carboxylate
  参考文献：
  名称：

  Discovery and Optimization of an Azetidine Chemical Series As a Free Fatty Acid Receptor 2 (FFA2) Antagonist: From Hit to Clinic

  摘要：

  FFA2, also called GPR43, is a G-protein coupled receptor for short chain fatty acids which is involved in the mediation of inflammatory responses. A class of azetidines was developed as potent FFA2 antagonists. Multiparametric optimization of early hits with moderate potency and suboptimal ADME properties led to the identification of several compounds with nanomolar potency on the receptor combined with excellent pharmacokinetic (PK) parameters. The most advanced compound, 4-[[(R)-1-(benzo[b]thiophene-3-carbonyl)-2-methyl-azetidine-2-carbonyl]-(3-chloro-benzyl)-amino]-butyric acid 99 (GLPG0974), is able to inhibit acetate-induced neutrophil migration strongly in vitro and demonstrated ability to inhibit a neutrophil-based pharmacodynamic (PD) marker, CD11b activation-specific epitope [AE], in a human whole blood assay. All together, these data supported the progression of 99 toward next phases, becoming the first FFA2 antagonist to reach the clinic.

  DOI：

  10.1021/jm5012885

文献信息

• [EN] AZETIDINE DERIVATIVES USEFUL FOR THE TREATMENT OF METABOLIC AND INFLAMMATORY DISEASES<br/>[FR] DÉRIVÉS D'AZÉTIDINE UTILES POUR LE TRAITEMENT DE MALADIES MÉTABOLIQUES ET INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2012098033A1

  公开（公告）日：2012-07-26

  Compounds are disclosed that have a formula represented by the following: These compounds may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example inflammatory conditions, infectious diseases, autoimmune diseases, diseases involving impairment of immune cell functions, cardiometabolic diseases, and/or proliferative diseases.

  披露了具有以下表示的公式的化合物：这些化合物可以制备为药物组合物，并可用于预防和治疗包括人类在内的哺乳动物的各种疾病，例如炎症性疾病、传染病、自身免疫疾病、涉及免疫细胞功能受损的疾病、心脏代谢疾病和/或增殖性疾病，举例不限。
• NOVEL COMPOUNDS USEFUL FOR THE TREATMENT OF METABOLIC AND INFLAMMATORY DISEASES
  申请人：GALAPAGOS NV

  公开号：US20140371198A1

  公开（公告）日：2014-12-18

  Compounds are disclosed that have a formula represented by the following: These compounds may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example inflammatory conditions, infectious diseases, autoimmune diseases, diseases involving impairment of immune cell functions, cardiometabolic diseases, and/or proliferative diseases.

  本文披露了一系列具有以下公式表示的化合物：这些化合物可以制备为药物组合物，并可用于哺乳动物，包括人类，的预防和治疗各种疾病，例如炎症性疾病、传染病、自身免疫疾病、涉及免疫细胞功能障碍的疾病、心血管代谢疾病和/或增殖性疾病，仅为举例。