2,3-dihydro-2-(hydroxymethyl)-7H-1,4-dioxino<2,3-e>indole-8-carboxylic acid | 137578-51-9

• 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: 2,3-dihydro-2-(hydroxymethyl)-7H-1,4-dioxino<2,3-e>indole-8-carboxylic acid
• 英文别名: 2-(hydroxymethyl)-3,7-dihydro-2H-[1,4]dioxino[2,3-e]indole-8-carboxylic acid
• CAS: 137578-51-9
• 化学式: C₁₂H₁₁NO₅
• 分子量: 249.223
• InChiKey: JPDTTYROSRLDQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  91.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,3-dihydro-2-(hydroxymethyl)-7H-1,4-dioxino<2,3-e>indole-8-carboxylic acid 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 23.5h， 生成 2,3-dihydro-2-<<(p-tolylsulfonyl)oxy>methyl>-7H-1,4-dioxino<2,3-e>indole
  参考文献：
  名称：

  Novel indolodioxanes with antihypertensive effects: potent ligands for the 5-HT1A receptor

  摘要：

  The synthesis and biological evaluation of a new family of tricyclic indolodioxanes is described. These compounds all contain the 2,3-dihydro-7H-1,4-dioxino[2,3-e]indole nucleus and bear substituents at the 2 and/or 8 positions. Thirteen members of this class were prepared and shown to be potent ligands for the 5-HTA receptor, with several compounds displaying subnanomolar inhibition constants. These compounds also bind to the dopamine D-2 receptor, but generally with higher inhibition constants than those for 5-HT1A. Certain members of this novel structural class show in vivo activity in the mouse hypothermia assay. One of these compounds, U-86192A, has been shown to have antihypertensive effects in the cat, completely eliminating sympathetic nerve discharge at 1 mg/kg iv and lowering mean arterial pressure to 50% pretreatment levels. These effects can be reversed by the administration of spiperone, indicating that U-86192A is acting via a central serotonergic mechanism.

  DOI：

  10.1021/jm00094a021
• 作为产物：
  描述：

  3-(oxiranylmethoxy)-2-(phenylmethoxy)benzaldehyde 在 palladium on activated charcoal 4-二甲氨基吡啶 、 lithium hydroxide 、 四丁基氟化铵 、 sodium methylate 、 三乙胺 、 环己烯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 xylene 为溶剂， 反应 25.5h， 生成 2,3-dihydro-2-(hydroxymethyl)-7H-1,4-dioxino<2,3-e>indole-8-carboxylic acid
  参考文献：
  名称：

  Novel indolodioxanes with antihypertensive effects: potent ligands for the 5-HT1A receptor

  摘要：

  The synthesis and biological evaluation of a new family of tricyclic indolodioxanes is described. These compounds all contain the 2,3-dihydro-7H-1,4-dioxino[2,3-e]indole nucleus and bear substituents at the 2 and/or 8 positions. Thirteen members of this class were prepared and shown to be potent ligands for the 5-HTA receptor, with several compounds displaying subnanomolar inhibition constants. These compounds also bind to the dopamine D-2 receptor, but generally with higher inhibition constants than those for 5-HT1A. Certain members of this novel structural class show in vivo activity in the mouse hypothermia assay. One of these compounds, U-86192A, has been shown to have antihypertensive effects in the cat, completely eliminating sympathetic nerve discharge at 1 mg/kg iv and lowering mean arterial pressure to 50% pretreatment levels. These effects can be reversed by the administration of spiperone, indicating that U-86192A is acting via a central serotonergic mechanism.

  DOI：

  10.1021/jm00094a021

文献信息

• Therapeutic agents
  申请人：——

  公开号：US20010008903A1

  公开（公告）日：2001-07-19

  Compounds of formula I 1 and pharmaceutically acceptable salts thereof in which A is methylene or —O—; B is methylene or —O—; G 1 -G 2 -G 3 form a heteroaromatic or heteroaliphatic chain; g is 0, 1 or 2; U is an alkylene chain optionally substituted by one or more alkyl; Q represents a divalent group containing nitrogen atoms; and T is an optionally substituted aryl or heteroaryl group, have utility in the treatment of central nervous system disorders, for example depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, Parkinson's disease, obesity, hypertension, Tourette's syndrome, sexual dysfunction, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, obsessive-compulsive behaviour, panic attacks, social phobias, eating disorders and anorexia, cardiovascular and cerebrovascular disorders, non-insulin dependent diabetes mellitus, hyperglycaemia, constipation, arrhythmia, disorders of the neuroendocrine system, stress, and spasticity.

  公式I1的化合物及其药学上可接受的盐，其中A是亚甲基或-O-；B是亚甲基或-O-；G1-G2-G3形成杂环芳香族或杂环脂肪族链；g为0、1或2；U是一条烷基链，可选择性地被一个或多个烷基取代；Q代表含有氮原子的二价基团；T是可选择性取代的芳基或杂环基团。这些化合物在治疗中枢神经系统疾病方面具有实用价值，例如抑郁症、焦虑症、精神病（例如精神分裂症）、迟发性运动障碍、帕金森病、肥胖症、高血压、图雷特综合症、性功能障碍、药物成瘾、药物滥用、认知障碍、阿尔茨海默病、老年痴呆症、强迫症、惊恐发作、社交恐惧症、进食障碍和厌食症、心血管和脑血管疾病、非胰岛素依赖性糖尿病、高血糖、便秘、心律失常、神经内分泌系统疾病、压力和痉挛症。
• HETEROARYLCARBOXAMIDE DERIVATIVES
  申请人：Knoll GmbH

  公开号：EP0876372B1

  公开（公告）日：2002-03-06
• DIOXINO DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS
  申请人：KNOLL AKTIENGESELLSCHAFT

  公开号：EP0966470A1

  公开（公告）日：1999-12-29
• US6107310A
  申请人：——

  公开号：US6107310A

  公开（公告）日：2000-08-22
• US6201004B1
  申请人：——

  公开号：US6201004B1

  公开（公告）日：2001-03-13