methyl 1-methylindoline-6-carboxylate | 1071432-28-4

• 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: methyl 1-methylindoline-6-carboxylate
• 英文别名: methyl 1-methyl-2,3-dihydro-1H-indole-6-carboxylate；methyl 1-methyl-2,3-dihydroindole-6-carboxylate
• CAS: 1071432-28-4
• 化学式: C₁₁H₁₃NO₂
• 分子量: 191.23
• InChiKey: KQJMBLOFMLWTAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 1-methylindoline-6-carboxylate 在 hydrazine hydrate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  5-Phenyl-1,3,4-oxadiazol-2(3H)-ones Are Potent Inhibitors of Notum Carboxylesterase Activity Identified by the Optimization of a Crystallographic Fragment Screening Hit

  摘要：

  Carboxylesterase Notum is a negative regulator of the Wnt signaling pathway. There is an emerging understanding of the role Notum plays in disease, supporting the need to discover new small-molecule inhibitors. A crystallographic X-ray fragment screen was performed, which identified fragment hit 1,2,3-triazole 7 as an attractive starting point for a structure-based drug design hit-to-lead program. Optimization of 7 identified oxadiazol-2-one 23dd as a preferred example with properties consistent with druglike chemical space. Screening 23dd in a cell-based TCF/LEF reporter gene assay restored the activation of Wnt signaling in the presence of Notum. Mouse pharmacokinetic studies with oral administration of 23dd demonstrated good plasma exposure and partial blood-brain barrier penetration. Significant progress was made in developing fragment hit 7 into lead 23dd (>600-fold increase in activity), making it suitable as a new chemical tool for exploring the role of Notum-mediated regulation of Wnt signaling.

  DOI：

  10.1021/acs.jmedchem.0c01391
• 作为产物：
  描述：

  吲哚-6-甲酸甲酯 在 sodium hydride 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.17h， 生成 methyl 1-methylindoline-6-carboxylate
  参考文献：
  名称：

  [EN] COMPOUNDS
  [FR] COMPOSÉS

  摘要：

  一种用于治疗通过抑制公式（I）中的Notum改善的疾病的化合物：（I）

  公开号：

  WO2020043866A1

文献信息

• AMINO-PYRROLIDINE-AZETIDINE DIAMIDES AS MONOACYLGLYCEROL LIPASE INHIBITORS
  申请人：Zhang Yue-Mei

  公开号：US20120101081A1

  公开（公告）日：2012-04-26

  Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds, and enantiomers, diastereomers, and pharmaceutically acceptable salts thereof, are represented by Formula (I) as follows: wherein Y, Z, and R 1 , and R 2 are defined herein.

  揭示了用于治疗各种疾病、综合症、症状和紊乱的化合物、组合物和方法，包括疼痛。这些化合物及其对映体、顺反异构体和药用盐由以下式(I)所代表：其中Y、Z、R1和R2在此处定义。
• ORNITHINE DERIVATIVE
  申请人：Astellas Pharma Inc.

  公开号：EP2141147A1

  公开（公告）日：2010-01-06

  Provided is a compound which is useful as a therapeutic agent for chronic renal insufficiency and a therapeutic agent for diabetic nephropathy. The present inventors have made extensive studies on an ornithine derivative having an antagonistic action against an EP4 receptor, and as a result, they have found that by introducing cycloalkanediyl at a C terminal of the ornithine part of the compound of the present invention, the physicochemical properties such as solubility, and the like can be improved, thereby giving further preferred properties as a pharmaceutical. Therefore, they have completed the present invention. The compound of the present invention exhibits a good antagonistic action against an EP4 receptor, and thus, it is useful as a therapeutic agent for chronic renal insufficiency and diabetic nephropathy.

  提供了一种化合物，可用作慢性肾功能不全的治疗剂和糖尿病肾病的治疗剂。目前的发明人对具有对EP4受体拮抗作用的鸟氨酸衍生物进行了广泛研究，结果发现通过在目前发明的化合物的鸟氨酸部分的C末端引入环烷基，可以改善物理化学性质，如溶解性等，从而赋予其作为药物的更优越性质。因此，他们完成了这项发明。目前发明的化合物对EP4受体表现出良好的拮抗作用，因此，它可用作慢性肾功能不全和糖尿病肾病的治疗剂。
• [EN] UREA-CONTAINING ISOXAZOLE DERIVATIVES AS FXR AGONISTS AND METHODS OF USE THEREOF<br/>[FR] DÉRIVÉS D'ISOXAZOLE CONTENANT DE L'URÉE UTILISÉS COMME AGONISTES DE FXR ET LEURS PROCÉDÉS D'UTILISATION
  申请人：ENANTA PHARM INC

  公开号：WO2018081285A1

  公开（公告）日：2018-05-03

  The present invention provides compounds of Formula (I), Pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising these compounds and methods of using these compounds to prevent or treat FXR- mediated or TGR5-mediated diseases or conditions.

  本发明提供了式(I)的化合物，其药学上可接受的盐，包含这些化合物的药物组合物以及使用这些化合物预防或治疗FXR介导或TGR5介导的疾病或症状的方法。
• Ornithine derivative
  申请人：Astellas Pharma Inc.

  公开号：US08030489B2

  公开（公告）日：2011-10-04

  Provided is a compound which is useful as a therapeutic agent for chronic renal insufficiency and a therapeutic agent for diabetic nephropathy. The present inventors have made extensive studies on an ornithine derivative having an antagonistic action against an EP4 receptor, and as a result, they have found that by introducing cycloalkanediyl at a C terminal of the ornithine part of the compound of the present invention, the physicochemical properties such as solubility, and the like can be improved, thereby giving further preferred properties as a pharmaceutical. Therefore, they have completed the present invention. The compound of the present invention exhibits a good antagonistic action against an EP4 receptor, and thus, it is useful as a therapeutic agent for chronic renal insufficiency and diabetic nephropathy.

  提供的是一种化合物，可用作慢性肾功能不全的治疗剂和糖尿病肾病的治疗剂。本发明人对具有对抗EP4受体作用的鸟氨酸衍生物进行了广泛的研究，结果发现通过在化合物的鸟氨酸部分的C末端引入环状烷基，可以改善其物理化学性质，例如溶解度等，从而赋予其更优越的药物特性。因此，他们完成了本发明。本发明的化合物显示出良好的对抗EP4受体的作用，因此可用作慢性肾功能不全和糖尿病肾病的治疗剂。
• AZETIDINYL DIAMIDES AS MONOACYLGLYCEROL LIPASE INHIBITORS
  申请人：Janssen Pharmaceutica, NV

  公开号：US20130217669A1

  公开（公告）日：2013-08-22

  Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: wherein Y, Z, R 1 , and s are defined herein.

  本发明涉及化合物、组合物和方法，用于治疗各种疾病、综合症、病况和障碍，包括疼痛。这些化合物由以下式子（I）所表示：其中，Y、Z、R1和s如下所定义。