2-(Benzylamino-methyl)-6-chloro-chroman-7-ol | 197388-11-7

• 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: 2-(Benzylamino-methyl)-6-chloro-chroman-7-ol
• 英文别名: 2-(Benzylamino-methyl)-6-chloro-chroman-7-ol; oxalic acid；2-[(benzylamino)methyl]-6-chloro-3,4-dihydro-2H-chromen-7-ol
• CAS: 197388-11-7
• 化学式: C₁₇H₁₈ClNO₂
• 分子量: 303.788
• InChiKey: BCTPODDQZONFKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  41.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(Benzylamino-methyl)-6-chloro-chroman-7-ol 生成 (S)-2-(Benzylamino-methyl)-6-chloro-chroman-7-ol
  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
• 作为产物：
  描述：

  (3,4-dihydro-7-methoxy-2H-chromen-2-yl)methanol 在 吡啶 、 N-氯代丁二酰亚胺 、 氢溴酸 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 97.0h， 生成 2-(Benzylamino-methyl)-6-chloro-chroman-7-ol
  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

• US5670667A
  申请人：——

  公开号：US5670667A

  公开（公告）日：1997-09-23