dihydrexidine | 174691-84-0

• 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
• 英文名称: dihydrexidine
• 英文别名: (+)-Dihydrexidine；(6aR,12bS)-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine-10,11-diol
• CAS: 174691-84-0；123039-93-0
• 化学式: C₁₇H₁₇NO₂
• 分子量: 267.327
• InChiKey: BGOQGUHWXBGXJW-RHSMWYFYSA-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

反应信息

• 作为反应物：
  描述：

  dihydrexidine 在 盐酸 作用下， 生成 (+)-Dihydrexidine hydrochloride
  参考文献：
  名称：

  一种新型高效合成二氢己定

  摘要：

  高产率地实现了多巴胺D 1选择性全激动剂二氢己定的有效合成，并且不需要通过（硝基丙基）二苯甲酮的分子内亨利环化和随后的非对映异构选择性还原得到的三环硝基烯而进行色谱分离。 酰化-分子内Henry反应-硝基烯烃-全合成。

  DOI：

  10.1055/s-0028-1083359
• 作为产物：
  描述：

  1-bromo-2-trityloxymethylbenzene 在 盐酸 、 正丁基锂 、 三溴化硼 、 potassium carbonate 、 锌 、 (1S,2S)-1-dimethylamino-2-(2-methoxyphenoxy)-1,2-diphenylethane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 甲苯 、 叔丁醇 为溶剂， 反应 38.67h， 生成 dihydrexidine
  参考文献：
  名称：

  Improved asymmetric synthesis of dopamine D1 full agonist, dihydrexidine, employing chiral ligand-controlled asymmetric conjugate addition of aryllithium to a nitroalkene

  摘要：

  Asymmetric conjugate addition of 2-trityloxymethylpheyllithium to a nitroalkene was mediated by a chiral ligand to give the key intermediate for dopamine D1 full agonist dihydrexidine 1. The shortcut of both Curtius rearrangement and Pictet-Spengler type cyclization, which were the drawback of the previously reported synthesis involving asymmetric conjugate addition of phenyllithium to an enoate, was realized by the newly developed asymmetric reaction. Short and efficient synthetic way gave optically pure dihydrexidine in 45% overall yield via eight steps. Improved synthesis of the best chiral ligand 13 was realized under the Buchwald conditions. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.03.039

文献信息

• Co-administration of dopamine-receptor binding compounds
  申请人：Fernandes B. Prabhavathi

  公开号：US20070155720A1

  公开（公告）日：2007-07-05

  Methods for treating a patient having neurological, psychotic, and psychiatric disorders are described comprising the steps of administering to the patient an effective amount of a partial and/or full dopamine D 1 receptor agonist, and administering to the patient an effective amount of a dopamine D 2 receptor antagonist. Pharmaceutical compositions comprising a dopamine D 1 receptor agonist and a dopamine D 2 receptor antagonist are also described. The D 1 dopamine receptor agonist and the D 2 dopamine receptor antagonist can be administered to the patient in the same or in a different composition or compositions.

  描述了治疗患有神经、精神和精神障碍的患者的方法，包括向患者施用部分和/或全多巴胺D1受体激动剂的有效量，并向患者施用多巴胺D2受体拮抗剂的有效量。还描述了包含多巴胺D1受体激动剂和多巴胺D2受体拮抗剂的药物组合物。D1多巴胺受体激动剂和D2多巴胺受体拮抗剂可以以相同或不同的组合或组合物形式向患者施用。
• Method of treatment of dopamine-related dysfunction
  申请人：——

  公开号：US20020132827A1

  公开（公告）日：2002-09-19

  The present invention relates to the treatment of dopamine-related dysfunction using full D 1 dopamine receptor agonists in an intermittent dosing protocol with a short, but essential, “off-period.” The D 1 agonist concentration is reduced during the “off-period” to obtain a plasma concentration of agonist that suboptimally activates D 1 dopamine receptors for a period of time to prevent induction of tolerance. Specifically, the method comprises the steps of periodically administering to a patient a full D 1 agonist with a half-life of up to about 6 hours at a dose resulting in a first plasma concentration of agonist capable of activating D 1 dopamine receptors to produce a therapeutic effect. The dose is reduced at least once every 24 hours to obtain a second lower plasma concentration of agonist that results in suboptimal activation of D 1 dopamine receptors for a period of time sufficient to prevent induction of tolerance.

  本发明涉及使用全D1多巴胺受体激动剂在间歇性给药方案中治疗多巴胺相关功能障碍，该方案具有一个短暂但关键的“停药期”。在“停药期”期间，将D1激动剂浓度降低，以获得一段时间的亚最佳激活D1多巴胺受体的激动剂血浆浓度，从而防止耐受性的诱导。具体而言，该方法包括定期向患者施用半衰期长达约6小时的全D1激动剂，剂量产生能够激活D1多巴胺受体以产生治疗效果的第一血浆浓度。至少每24小时减少一次剂量，以获得较低的第二血浆浓度，该浓度导致一段时间的亚最佳激活D1多巴胺受体，足以防止耐受性的诱导。
• Trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine: a highly potent selective dopamine D1 full agonist
  作者：William K. Brewster、David E. Nichols、Robert M. Riggs、David M. Mottola、Timothy W. Lovenberg、Mark H. Lewis、Richard B. Mailman

  DOI：10.1021/jm00168a034

  日期：1990.6

  versus [3H]spiperone. These data demonstrate that dihydroxidine has about ten-fold selectivity for D1/D2 receptors. More importantly, however, is the fact that dihydrexidine is a full agonist. Previously available agents, such as SKF38393 (1b), while being somewhat more selective for the D1 receptor, are only partial agonists. The isomeric cis-dihydroxybenzo[a]-phenanthridine neither stimulated cAMP synthesis

  已发现反式-10,11-二羟基-5,6,6a，7,8,12b-六氢苯并[a]菲啶（4a，dihydrexidine）是大鼠脑中多巴胺D1受体的强效选择性激动剂。在激活多巴胺敏感性大鼠纹状体腺苷酸环化酶时，二氢己啶的EC50约为70 nM，最大刺激等于或稍大于多巴胺产生的刺激。在竞争大鼠纹状体匀浆中的[3H] SCH23390（1a）结合位点时，二氢己啶的IC50为12 nM，而与[3H]哌酮相比则为120 nM。这些数据证明二氢吡啶对D1 / D2受体具有约十倍的选择性。然而，更重要的是二氢己定是完全激动剂的事实。先前可用的试剂，例如SKF38393（1b），虽然对D1受体的选择性更高，但仅是部分激动剂。异构体顺式-二羟基苯并[a]-菲啶既不刺激cAMP的合成，也不抑制多巴胺诱导的cAMP的合成。顺式异构体也缺乏对[3H] -1a结合位点的亲和力。标题化合物的N-甲基化使对D1位点的亲和力
• [EN] NOVEL FUSED ISOQUINOLINES AS DOPAMINE RECEPTOR LIGANDS<br/>[FR] NOUVELLES ISOQUINOLEINES FUSIONNEES UTILISEES EN TANT QUE LIGANDS POUR RECEPTEURS DE LA DOPAMINE
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO1997006799A1

  公开（公告）日：1997-02-27

  (EN) The present invention is directed to novel dopamine receptor ligands of formula (I), pharmaceutical formulations of such compounds, and a method using such compounds for treating a patient suffering from dopamine-related dysfunction of the central or peripheral nervous system.(FR) L'invention se rapporte à des nouveaux ligands pour récepteurs de la dopamine, représentés par la formule (I), les formulations pharmaceutiques de ces composés, et un procédé dans lequel ces composés sont utilisés pour traiter un patient souffrant d'un dysfonctionnement du système nerveux périphérique ou central, lié à la dopamine.

  本发明涉及公式（I）的新型多巴胺受体配体、这些化合物的制药配方，以及使用这些化合物治疗患有中枢或外周神经系统多巴胺相关功能障碍的患者的方法。
• Method of Administration of Dopamine Receptor Agonists
  申请人：Fernandes B. Prabhavathi

  公开号：US20070254906A1

  公开（公告）日：2007-11-01

  Methods for treating a patient having pulmonary edema are described. The methods include administering to the lung endobronchial space of the airways of the patient an effective amount of a dopamine D 1 receptor agonist. Dopamine D 1 receptor agonists, including hexahydrobenzophenanthridine, hexahydrothienophenanthridine, phenyltetrahydrobenzazepine, chromenoisoquinoline, naphthoisoquinoline dopamine receptor agonists, and their pharmaceutically acceptable salts, formulated as aerosols and dry powders are also described.

  本文描述了治疗肺水肿患者的方法。该方法包括向患者的呼吸道肺内支气管空间内注射有效量的多巴胺D1受体激动剂。本文还介绍了多巴胺D1受体激动剂，包括六氢苯并苯并芳烃、六氢噻吩并芳烃、苯基四氢苯并氮杂环、香豆素异喹啉、萘异喹啉多巴胺受体激动剂及其药学上可接受的盐，制成气溶胶和干粉。