N-(2-{[3-(3-nitro-phenoxy)-propylamino]-methyl}-chroman-7-yl)-methanesulfonamide | 195453-81-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-{[3-(3-nitro-phenoxy)-propylamino]-methyl}-chroman-7-yl)-methanesulfonamide
• 英文别名: N-[2-[[3-(3-nitrophenoxy)propylamino]methyl]-3,4-dihydro-2H-chromen-7-yl]methanesulfonamide
• CAS: 195453-81-7
• 化学式: C₂₀H₂₅N₃O₆S
• 分子量: 435.501
• InChiKey: ZEQDVGUUQCDLGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(2-{[3-(3-nitro-phenoxy)-propylamino]-methyl}-chroman-7-yl)-methanesulfonamide 在 aluminum nickel 肼 作用下， 以 乙醇 为溶剂， 以69.9%的产率得到N-(2-{[3-(3-amino-phenoxy)-propylamino]-methyl}-chroman-7-yl)-methanesulfonamide
  参考文献：
  名称：

  Chroman-2-ylmethylamino derivatives

  摘要：

  本文描述的是以下化合物：##STR1## 其中n为1、2或3；m为0或1；R为取代或未取代的苯基，其中取代基独立地为从烷基、羟基、卤素或氨基组成的一种或两种成员，或者R为1至6个碳原子的烷基或1至6个碳原子的羟基烷基；或其药学上可接受的盐，这些化合物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、图雷特综合症、酒精成瘾、可卡因成瘾和类似药物成瘾。

  公开号：

  US05663194A1
• 作为产物：
  描述：

  N-(4-乙酰基-3-羟基苯基)乙酰胺 在 palladium on activated charcoal 吡啶 、 盐酸 、 锂硼氢 、 氢气 、 sodium ethanolate 、 potassium carbonate 、 溶剂黄146 、 sodium iodide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、344.73 kPa 条件下， 反应 164.9h， 生成 N-(2-{[3-(3-nitro-phenoxy)-propylamino]-methyl}-chroman-7-yl)-methanesulfonamide
  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：——

  公开号：US05663194A1

  公开（公告）日：1997-09-02

  Described herein are compounds of the formula: ##STR1## in which n is 1, 2 or 3; m is 0 or 1; and R is a substituted or unsubstituted phenyl group in which the substitutents are, independently, one or two members selected from the group consisting of alkyl, hydroxy, halo or amino groups or R is alkyl of 1 to 6 carbon atoms or hydroxyalkyl of 1 to 6 carbon atoms; or a pharmaceutically acceptable salt thereof, which are inhibitors of dopamine synthesis and release, and are useful in the treatment of schizophrenia, Parkinson's Disease, Tourette's Syndrome, alcohol addiction, cocaine addiction, and addiction to analagous drugs.

  本文描述的是以下化合物：##STR1## 其中n为1、2或3；m为0或1；R为取代或未取代的苯基，其中取代基独立地为从烷基、羟基、卤素或氨基组成的一种或两种成员，或者R为1至6个碳原子的烷基或1至6个碳原子的羟基烷基；或其药学上可接受的盐，这些化合物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、图雷特综合症、酒精成瘾、可卡因成瘾和类似药物成瘾。
• US5663194A
  申请人：——

  公开号：US5663194A

  公开（公告）日：1997-09-02
• 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.