(5-hydroxy-2-methyl-1H-indol-3-yl)-morpholin-4-yl-methanone | 118052-59-8

• 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: (5-hydroxy-2-methyl-1H-indol-3-yl)-morpholin-4-yl-methanone
• 英文别名: (5-hydroxy-2-methyl-1H-indol-3-yl)-morpholin-4-ylmethanone
• CAS: 118052-59-8
• 化学式: C₁₄H₁₆N₂O₃
• 分子量: 260.293
• InChiKey: OFQPNTIOOLHYIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  65.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-异丙基-4-哌啶醇 、 (5-hydroxy-2-methyl-1H-indol-3-yl)-morpholin-4-yl-methanone 在 三丁基膦 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 为溶剂， 以22%的产率得到[5-(1-isopropyl-piperidin-4-yloxy)-2-methyl-1H-indol-3-yl]-morpholin-4-yl-methanone
  参考文献：
  名称：

  5-Hydroxyindole-2-carboxylic Acid Amides: Novel Histamine-3 Receptor Inverse Agonists for the Treatment of Obesity

  摘要：

  Obesity is a major risk factor in the development of conditions such as hypertension, hyperglycemia, dyslipidemia, coronary artery disease, and cancer. Several pieces of evidence across different species, including primates, underscore the implication of the histamine 3 receptor (H3R) in the regulation of food intake and body weight and the potential therapeutic effect Of H3R inverse agonists. A pharmacophore model, based on public information and validated by previous investigations, was used to design several potential scaffolds. Out of these scaffolds. the 5-hydroxyindole-2-carboxylic acid amide appeared to be of great potential as a novel series of H-3 inverse agonist. Extensive structure-activity relationships revealed the interconnectivity of microsomal clearance and hERG (human ether-a-go-go-related gene) affinity with lipophilicity, artificial membrane permeation, and basicity. This effort led to the identification of compounds reversing the (R)-alpha-methylhistamine-induced water intake increase in Wistar rats and, further, reducing food intake in diet-induced obese Sprague-Dawley rats. Of these, the biochemical, pharmacokinetic, and pharmacodynamic characteristics of (4,4-difluoropiperidin-1-yl)[1-isopropyl-5-(1-isopropylpiperidin-4-yloxy)1H-indol-2-yl]-methanone 36 are detailed.

  DOI：

  10.1021/jm900409x
• 作为产物：
  描述：

  吗啉 、 5-羟基-2-甲基-1H-吲哚-3-羧酸 在 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以20%的产率得到(5-hydroxy-2-methyl-1H-indol-3-yl)-morpholin-4-yl-methanone
  参考文献：
  名称：

  5-Hydroxyindole-2-carboxylic Acid Amides: Novel Histamine-3 Receptor Inverse Agonists for the Treatment of Obesity

  摘要：

  Obesity is a major risk factor in the development of conditions such as hypertension, hyperglycemia, dyslipidemia, coronary artery disease, and cancer. Several pieces of evidence across different species, including primates, underscore the implication of the histamine 3 receptor (H3R) in the regulation of food intake and body weight and the potential therapeutic effect Of H3R inverse agonists. A pharmacophore model, based on public information and validated by previous investigations, was used to design several potential scaffolds. Out of these scaffolds. the 5-hydroxyindole-2-carboxylic acid amide appeared to be of great potential as a novel series of H-3 inverse agonist. Extensive structure-activity relationships revealed the interconnectivity of microsomal clearance and hERG (human ether-a-go-go-related gene) affinity with lipophilicity, artificial membrane permeation, and basicity. This effort led to the identification of compounds reversing the (R)-alpha-methylhistamine-induced water intake increase in Wistar rats and, further, reducing food intake in diet-induced obese Sprague-Dawley rats. Of these, the biochemical, pharmacokinetic, and pharmacodynamic characteristics of (4,4-difluoropiperidin-1-yl)[1-isopropyl-5-(1-isopropylpiperidin-4-yloxy)1H-indol-2-yl]-methanone 36 are detailed.

  DOI：

  10.1021/jm900409x

文献信息

• 5-HYDROXYINDOLE-3-CARBOXAMIDE COMPOUND AND MEDICINAL USE THEREOF
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：EP0299076A1

  公开（公告）日：1989-01-18

  5-Hydroxyindole-3-carboxamide compounds represented by general formula (I), may be the same or different, each represents a hydrogen atom or an aklyl, aryl, aralkyl or heteroaryl group, or R1 and R2, or R3 and R4, are bound to each other to form a heterocyclic ring togetherwith the adjacent nitrogen atom, R5 represents an alkyl group, R6 represents a hydrogen atom or an alkyl, cycloalkyl, aryl or aralkyl group, and X represents a hydrogen or halogen atom or a lower alkanoyl group) and acid addition salts thereof. These compounds are useful as diuretics or drugs for treating diseases of human circulatory organs.

  通式 (I) 所代表的 5-羟基吲哚-3-甲酰胺化合物、 R1和R2或R3和R4相互结合，与相邻的氮原子一起形成杂环，R5代表烷基，R6代表氢原子或烷基、环烷基、芳基或芳烷基，X代表氢原子、卤素原子或低级烷酰基）及其酸加成盐。这些化合物可用作利尿剂或治疗人体循环器官疾病的药物。
• TAHARA, TETSUYA;IKEBE, TSUGUO;HAKAMADA, ICHIRO;YAOKA, OSAMU
  作者：TAHARA, TETSUYA、IKEBE, TSUGUO、HAKAMADA, ICHIRO、YAOKA, OSAMU

  DOI：——

  日期：——
• US4874759A
  申请人：——

  公开号：US4874759A

  公开（公告）日：1989-10-17