(7-methoxy-chroman-2-ylmethyl)-(3-phenoxy-propyl)-amine | 197388-31-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (7-methoxy-chroman-2-ylmethyl)-(3-phenoxy-propyl)-amine
• 英文别名: N-[(7-methoxy-3,4-dihydro-2H-chromen-2-yl)methyl]-3-phenoxypropan-1-amine
• CAS: 197388-31-1
• 化学式: C₂₀H₂₅NO₃
• 分子量: 327.423
• InChiKey: LJAIUTWQPYZQQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  39.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (7-methoxy-chroman-2-ylmethyl)-(3-phenoxy-propyl)-amine 以 甲醇 、 aqueous HBr 、 二氯甲烷 为溶剂， 生成 2-[(3-Phenoxy-propylamino)-methyl]-chroman-7-ol
  参考文献：
  名称：

  Chroman-2-ylmethylamino derivatives

  摘要：

  分子式为：##STR1## 其中Z为氢或卤素；n为整数1、2、3或4之一；m为整数0或1之一；R为取代或未取代的芳基基团，其中取代基独立地为烷基、羟基、卤素或氨基中的一个或两个成员；R.sup.2为氢或烷基；或其药学上可接受的盐，是多巴胺合成和释放的抑制剂，可用于治疗精神分裂症、帕金森病、杜雷特综合症、酒精成瘾、可卡因成瘾和类似药物成瘾。

  公开号：

  US05670667A1
• 作为产物：
  描述：

  ethyl 3,4-dihydro-7-methoxy-2H-chromene-2-carboxylate 在 锂硼氢 、 四溴化碳 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 (7-methoxy-chroman-2-ylmethyl)-(3-phenoxy-propyl)-amine
  参考文献：
  名称：

  New Generation Dopaminergic Agents. 1. Discovery of a Novel Scaffold Which Embraces the D₂ Agonist Pharmacophore. Structure−Activity Relationships of a Series of 2-(Aminomethyl)chromans

  摘要：

  A series of 2-(aminomethyl)chromans (2-AMCs) was synthesized and evaluated for their affinity and selectivity for both the high-and low-affinity agonist states (D-2(High) and D-2(Low), respectively) of the dopamine (DA) D-2 receptor. The 7-hydroxy-2-(aminomethyl)chroman moiety was observed to be the primary D-2 agonist pharmacophore. The 2-methylchroman moiety was discovered to be an entirely novel scaffold which could be used to access the D-2 agonist pharmacophore. Attaching various simple alkyl and arylalkyl side chains to the 7-hydroxy 2-AMC nucleus had significant effects on selectivity for the D-2(High) receptor vs the 5HT(1A) and alpha(1) receptors. A novel DA partial agonist, (R)-(-)-2-(benzylamino)methyl)chroman-7-ol [R-(-)-35c], was identified as having the highest affinity and best selectivity for the D-2(High) receptor vs the alpha(1) and 5HT(1A) receptors. Several regions of the 2-AMC nucleus were modified and recognized as potential sites to modulate the level of intrinsic activity. The global minimum conformer of the 7-hydroxy-2-AMC moiety was identified as fulfilling the McDermed model D-2 agonist pharmacophoric criteria and was proposed as the D-2 receptor-bound conformation. Structure-activity relationships gained from these studies have aided in the synthesis of D-2 partial agonists of varying intrinsic activity levels. These agents should be of therapeutic value in treating disorders resulting from hypo-and hyperdopaminergic activity, without the side effects associated with complete D-2 agonism or antagonism.

  DOI：

  10.1021/jm9703653

文献信息

• Chroman-2-ylmethylamino derivatives
  申请人：American Home Products Corporation

  公开号：US05670667A1

  公开（公告）日：1997-09-23

  Compounds of the formula: ##STR1## in which Z is hydrogen or a halogen; n is one of the integers 1, 2, 3, or 4; m is one of the integers 0 or 1; R is a substituted or unsubstituted aryl group in which the substituents are, independently, one or two members selected from the group consisting of alkyl, hydroxy, halo or amino groups; R.sup.2 is hydrogen or alkyl; or a pharmaceutically acceptable salt thereof, are inhibitors of dopamine synthesis and release, useful in the treatment of schizophrenia, Parkinson's Disease, Tourette's Syndrome, alcohol addiction, cocaine addiction, and addiction to analagous drugs.

  分子式为：##STR1## 其中Z为氢或卤素；n为整数1、2、3或4之一；m为整数0或1之一；R为取代或未取代的芳基基团，其中取代基独立地为烷基、羟基、卤素或氨基中的一个或两个成员；R.sup.2为氢或烷基；或其药学上可接受的盐，是多巴胺合成和释放的抑制剂，可用于治疗精神分裂症、帕金森病、杜雷特综合症、酒精成瘾、可卡因成瘾和类似药物成瘾。
• US5670667A
  申请人：——

  公开号：US5670667A

  公开（公告）日：1997-09-23
• New Generation Dopaminergic Agents. 1. Discovery of a Novel Scaffold Which Embraces the D₂ Agonist Pharmacophore. Structure−Activity Relationships of a Series of 2-(Aminomethyl)chromans
  作者：Richard E. Mewshaw、Joseph Kavanagh、Gary Stack、Karen L. Marquis、Xiaojie Shi、Michael Z. Kagan、Michael B. Webb、Alan H. Katz、Anna Park、Young H. Kang、Magid Abou-Gharbia、Rosemary Scerni、Theodore Wasik、Luz Cortes-Burgos、Taylor Spangler、Julie A. Brennan、Michael Piesla、Hossein Mazandarani、Mark I. Cockett、Rafal Ochalski、Joseph Coupet、Terrance H. Andree

  DOI：10.1021/jm9703653

  日期：1997.12.1

  A series of 2-(aminomethyl)chromans (2-AMCs) was synthesized and evaluated for their affinity and selectivity for both the high-and low-affinity agonist states (D-2(High) and D-2(Low), respectively) of the dopamine (DA) D-2 receptor. The 7-hydroxy-2-(aminomethyl)chroman moiety was observed to be the primary D-2 agonist pharmacophore. The 2-methylchroman moiety was discovered to be an entirely novel scaffold which could be used to access the D-2 agonist pharmacophore. Attaching various simple alkyl and arylalkyl side chains to the 7-hydroxy 2-AMC nucleus had significant effects on selectivity for the D-2(High) receptor vs the 5HT(1A) and alpha(1) receptors. A novel DA partial agonist, (R)-(-)-2-(benzylamino)methyl)chroman-7-ol [R-(-)-35c], was identified as having the highest affinity and best selectivity for the D-2(High) receptor vs the alpha(1) and 5HT(1A) receptors. Several regions of the 2-AMC nucleus were modified and recognized as potential sites to modulate the level of intrinsic activity. The global minimum conformer of the 7-hydroxy-2-AMC moiety was identified as fulfilling the McDermed model D-2 agonist pharmacophoric criteria and was proposed as the D-2 receptor-bound conformation. Structure-activity relationships gained from these studies have aided in the synthesis of D-2 partial agonists of varying intrinsic activity levels. These agents should be of therapeutic value in treating disorders resulting from hypo-and hyperdopaminergic activity, without the side effects associated with complete D-2 agonism or antagonism.