(6aR,12bS)-10,11-dimethoxy-5,6,6a,7,8,12b-hexahydro-benzo[a]phenanthridine hydrochloride

• 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: (6aR,12bS)-10,11-dimethoxy-5,6,6a,7,8,12b-hexahydro-benzo[a]phenanthridine hydrochloride
• 英文别名: (6aR,12bS)-10,11-dimethoxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine;hydrochloride
• 化学式: C₁₉H₂₁NO₂*ClH
• 分子量: 331.842
• InChiKey: LUPPGEMWSNXEHG-LJLRIERRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.68
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  30.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6aR,12bS)-10,11-dimethoxy-5,6,6a,7,8,12b-hexahydro-benzo[a]phenanthridine hydrochloride 在 三溴化硼 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 dihydrexidine
  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：

  (1R,2R)-N-(6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-N-methoxymethyl-4-nitro-benzenesulfonamide 在 盐酸 、 4-甲氧基苯硫酚 、 三氟甲磺酸三甲基硅酯 、 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 二甲基亚砜 、 乙腈 为溶剂， 反应 7.0h， 生成 (6aR,12bS)-10,11-dimethoxy-5,6,6a,7,8,12b-hexahydro-benzo[a]phenanthridine hydrochloride
  参考文献：
  名称：

  Asymmetric synthesis of a dopamine D1 agonist, dihydrexidine from d-serine

  摘要：

  A scalable asymmetric synthesis of trans-2-amino-6,7-dimethoxy-1-phenyltetralin 2 and its N-nosyl derivative 12 have been achieved from Garner aldehyde derived from easily available D-serine using a stereoselective PhMgBr addition, Wittig reaction and TFA-mediated Friedel-Crafts cyclization as the key steps. The synthesis of dihydrexidine is accomplished from the N-nosyl-2-amino-1-phenyltetralin 12. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2011.08.014

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。
• Protecting group directed cyclization: asymmetric synthesis of both cis- and trans-dihydrexidine from a common precursor
  作者：Rajesh Malhotra、Sagar Chakrabarti、Tushar K. Dey、Swarup Dutta、Krishna Babu Alapati、Shantanu Dutta、Subho Roy、Sourav Basu、Saumen Hajra

  DOI：10.1016/j.tet.2013.08.042

  日期：2013.10

  Protection group of amino- and tethered o-arene functionality of 1,4-aryl-2-amino-1-butanol derived from l-serine dictates the cyclization mode under acidic conditions leading to reverse diastereoselectivity. N-Boc and acetal protected amino alcohol undergo cascade cyclization providing exclusively cis-dihydrexidine via reduction, where formation of C-ring (isoquinoline unit) prior to Friedel–Crafts

  保护基团的氨基和系留ö -arene衍生自1,4-芳基-2-氨基-1-丁醇的功能升丝氨酸使然酸性条件导致非对映选择性反转下环化模式。Ñ -Boc和乙缩醛保护的氨基醇进行环化级联提供专门的顺式-dihydrexidine通过还原，其中形成C形环（异喹啉单元）之前的Friedel-Crafts环化控制的顺式-立体化学的B环的。Ñ -Cbz和ö -苄基保护直接第一架F-C环化，得到的反式-1-芳基-2-氨基四氢化萘和随后的脱保护环化形成C形环，得到二羟西汀。
• 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
• Co-Administration of Dopamine-Receptor Binding Compounds
  申请人：Fernandes Prabhavathi B.

  公开号：US20100041690A1

  公开（公告）日：2010-02-18

  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.

  描述了治疗神经、精神和精神障碍患者的方法，包括向患者施用部分和/或完全的多巴胺D1受体激动剂的有效剂量，并向患者施用多巴胺D2受体拮抗剂的有效剂量。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在同一组合物或不同组合物中向患者施用。
• A Novel and Efficient Synthesis of Dihydrexidine
  作者：David Nichols、Juan Cueva

  DOI：10.1055/s-0028-1083359

  日期：——

  efficient synthesis of the dopamine D1 selective full agonist dihydrexidine has been achieved in high yields and requiring no chromatographic separations via a facilitated intramolecular Henry cyclization of a (nitropropyl)benzophenone and subsequent diastereomerically selective reduction of the resulting tricyclic nitroalkene. acylations - intramolecular Henry reaction - nitroalkene - total synthesis.

  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。