(R)-(+)-N-(1,4-benzodioxan-2-ylmethyl)-1-[1-(2-methoxyphenyl)piperid-4-yl]methylamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (R)-(+)-N-(1,4-benzodioxan-2-ylmethyl)-1-[1-(2-methoxyphenyl)piperid-4-yl]methylamine
• 英文别名: N-[[(3R)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]-1-[1-(2-methoxyphenyl)piperidin-4-yl]methanamine
• 化学式: C₂₂H₂₈N₂O₃
• 分子量: 368.476
• InChiKey: XYBADQIMVGSILK-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  43
• 氢给体数：
  1
• 氢受体数：
  5

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	1-[1-(2-methoxyphenyl)piperid-4-yl]methylamine	170353-24-9	C13H20N2O	220.315

反应信息

• 作为产物：
  描述：

  4-吡啶甲酰胺 在 palladium on activated charcoal lithium aluminium tetrahydride 、 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 124.0h， 生成 (R)-(+)-N-(1,4-benzodioxan-2-ylmethyl)-1-[1-(2-methoxyphenyl)piperid-4-yl]methylamine
  参考文献：
  名称：

  N-Substituted (2,3-Dihydro-1,4-benzodioxin-2-yl)methylamine Derivatives as D₂ Antagonists/5-HT_1A Partial Agonists with Potential as Atypical Antipsychotic Agents

  摘要：

  A series of N-substituted 1-(2,3-dihydro-1,4-benzodioxin-2-yl)methylamine derivatives with D-2 antagonist/5-HT1A partial agonist activity has been prepared as potential atypical antipsychotic agents. Optimization of in vitro receptor binding activity and in vivo activity in rodent models of psychosis has led to compound 24, which showed good affinities for human D-2, D-3, and 5-HT1A receptors but significantly less affinity for human alpha(1) adrenoceptors and rat H-1 and muscarinic receptors. In rodents, 24 showed functional D-2-like antagonism and 5-HT1A partial agonism. After oral dosing, 24 showed good activity in rodent antipsychotic tests and very little potential to cause extrapyramidal side effects (EPS), as measured by its ability to induce catalepsy in rats only at very high doses. In the light of this promising profile of activity, 24 has been selected for clinical investigation as a novel antipsychotic agent with a predicted low propensity to cause EPS.

  DOI：

  10.1021/jm9910122

文献信息

• Bicyclic aromatic compounds as therapeutic agents
  申请人：Knoll Atkiengesellschaft

  公开号：US05767116A1

  公开（公告）日：1998-06-16

  Compounds of formula I ##STR1## and pharmaceutically acceptable salts thereof in which A is methylene or --O--; B is methylene or --O--; and g is 0, 1, 2, 3 or 4; R.sub.1, R.sub.2, R.sub.3, R.sub.4, U, Q and T are defined in claim 1. The compounds 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, eating disorders and anorexia, cardiovascular and cerebrovascular disorders, non-insulin dependent diabetes mellitus, hyperglycaemia, constipation, arrhythmia, disorders of the neuroendocrine system, stress, prostatic hypertrophy, and spasticity.

  化合物I的结构如下，并且其药学上可接受的盐，其中A为亚甲基或--O--; B为亚甲基或--O--; g为0、1、2、3或4; R.sub.1、R.sub.2、R.sub.3、R.sub.4、U、Q和T的定义如索赔1所述。这些化合物在治疗中枢神经系统疾病方面具有用途，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、杜雷特综合征、性功能障碍、药物成瘾、药物滥用、认知障碍、阿尔茨海默病、老年性痴呆、强迫行为、惊恐发作、进食障碍和厌食症、心血管和脑血管疾病、非胰岛素依赖型糖尿病、高血糖、便秘、心律失常、神经内分泌系统疾病、压力、前列腺肥大和痉挛症。
• 1,4-Benzodioxane derivatives having affinity for D2 receptors and utility in the treatment of psychoses
  申请人：Knoll AG

  公开号：EP0717739B1

  公开（公告）日：2000-03-29
• BICYCLIC AROMATIC COMPOUNDS FOR TREATING DRUG ADDICTION
  申请人：Knoll GmbH

  公开号：EP1198234A2

  公开（公告）日：2002-04-24
• US5767116A
  申请人：——

  公开号：US5767116A

  公开（公告）日：1998-06-16
• [EN] THERAPEUTIC AGENTS<br/>[FR] AGENTS THERAPEUTIQUES
  申请人：KNOLL AG

  公开号：WO2001002391A2

  公开（公告）日：2001-01-11

  Compounds of formula (I) and pharmaceutically acceptable salts thereof in which A is methylene or -O-; B is methylene or -O-; and g is 0, 1, 2, 3 or 4; R1 represents, halo, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylthio, hydroxy, acyloxy, hydroxymethyl, cyano, alkanoyl, alkoxycarbonyl, optionally N-substituted carbamoyl, carbamoylmethyl, sulphamoyl or sulphamoylmethyl, an amino group optionally substituted by one or two alkyl groups, or two adjacent R1 groups together with the carbon atoms to which they are attached form a fused benz ring; R2 is H, alkyl or alkoxy; R3 and R4, which are the same or different, are H, or alkyl; U is an alkylene chain optionally substituted by one or more alkyl; Q represents a divalent group of formula (IIa, IIb or IIc) in which V is a bond or an alkylene chain optionally substituted by one or more alkyl; V' is an alkylene chain optionally substituted by one or more alkyl; X is a bond or an alkylene chain and X' is an alkylene chain, provided that the total number of carbon atoms in X and X' amounts to 3 or 4; R5 is H, or alkyl; and T represents an optionally substituted aromatic group which optionally contains one or more N atoms, provided that T is not 2-pyrimidinyl when A is -O-; have utility in reducing cravings to food or an addictive substance.