二受体激动剂盐酸盐 | 123039-93-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 二受体激动剂盐酸盐
• 英文名称: (6aS,12bR)-(-)-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzophenanthridine
• 英文别名: (6aS,12bR)-(-)-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydro-benzo[a]phenanthridine；Dihydrexidine；(6aS,12bR)-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine-10,11-diol
• CAS: 123039-93-0；757161-85-6
• 化学式: C₁₇H₁₇NO₂
• 分子量: 267.327
• InChiKey: BGOQGUHWXBGXJW-YOEHRIQHSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  52.5
• 氢给体数：
  3
• 氢受体数：
  3

上下游信息

反应信息

• 作为产物：
  描述：

  trans-10,11-dimethoxy-5,6,6a,7,8,12b-hexahydrobenzophenanthridine 以73的产率得到二受体激动剂盐酸盐
  参考文献：
  名称：

  Tetrahedron 2004, 60, 4237-4242

  摘要：

  DOI：

文献信息

• Dopaminergic Benzo[a]phenanthridines: Resolution and Pharmacological Evaluation of the Enantiomers of Dihydrexidine, the Full Efficacy D1 Dopamine Receptor Agonist
  作者：Timm A. Knoerzer、David E. Nichols、William K. Brewster、Val J. Watts、David Mottola、Richard B. Mailman

  DOI：10.1021/jm00041a025

  日期：1994.7

  Racemic trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine (2, dihydrexidine) was shown previously to be the first bioavailable full efficacy agonist at the D-1 dopamine receptor. In addition to its full D-1 agonist properties, 2 also is a good ligand for D-2-like dopamine receptors. The profound anti-Parkinsonian actions of this compound make determination of its enantioselectivity at both D-1 and D-2 receptors of particular importance. To accomplish this, the enantiomers were resolved by preparation of diastereomeric (R)-O-methylmandelic acid amides of racemic trans-10,11-dimethoxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine 4 that were then separated by centrifugal chromatography. An X-ray analysis of the (-)-N-(R)-O-methylmandel diastereoamide revealed the absolute configuration to be 6aS,12bR. Removal of the chiral auxiliary and O,O-deprotection afforded enantiomeric amines that were then tested for biological activity. In striatal membranes, the (6aR,12bS)-(+)-enantiomer 2 had about twice the affinity of the racemate and 25-fold greater affinity than the (-)-enantiomer at the D-1 receptor labeled by [H-3]SCH23390 (K(0.5)s of 5.6, 11.6, and 149 nM, respectively). Similarly, the (+)-enantiomer 2 had about twice the affinity of the racemate for human D-1 receptors expressed in transfected Ltk(-) cells. Functionally, the (+)-enantiomer of 2 was a full agonist, with an EC(50) of 51 nM in activating striatal dopamine-sensitive adenylate cyclase versus 2.15 mu M for the (-)-enantiomer. With respect to D-2-like receptors, (+)-2 had a K-0.5 of 87.7 nM in competing with [H-3]spiperone at D-2 binding sites in rat striatal membranes versus about 1 mu M for the (-)-enantiomer. Together, these data demonstrate that both the D-1 and D-2 activities of dihydrexidine reside principally in the (GaR,12bS)-(+)-enantiomer. The results are discussed in the context of structure-activity relationships and conceptual models of the D-1 receptor.
• Dual function drugs and uses thereof
  申请人：Altar A. Charles

  公开号：US20070142399A1

  公开（公告）日：2007-06-21

  Dual action compounds are provided that are inhibitors of catechol-omethyltransferase (COMT) enzyme and are also partial agonists or antagonists of the D2 receptor, or agonists of the D1 receptor, or interact in these ways with both D1 and D2 receptors. Use of the compounds for treating neuropsychiatric disorders, particularly schizophrenia and mild cognitive impairment, is also described.
• Tetrahedron 2004, 60, 4237-4242
  作者：

  DOI：——

  日期：——