西拉多巴 | 80109-27-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 西拉多巴
• 中文别名: 司拉多巴
• 英文名称: (-)2-<4-<2-hydroxy-2-(3',4'-dimethoxyphenyl)ethyl>-1-piperazinyl>-2,4,6-cycloheptatrien-1-one
• 英文别名: AY 27110；Ciladopa；2-[4-[(2S)-2-(3,4-dimethoxyphenyl)-2-hydroxyethyl]piperazin-1-yl]cyclohepta-2,4,6-trien-1-one
• CAS: 80109-27-9
• 化学式: C₂₁H₂₆N₂O₄
• 分子量: 370.448
• InChiKey: SGEKLKJQLHJVDK-LJQANCHMSA-N

物化性质

• 熔点：
  122-124 °C(Solv: chloroform (67-66-3); hexane (110-54-3))
• 沸点：
  571.6±50.0 °C(Predicted)
• 密度：
  1.213±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  62.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  西拉多巴 、 4-溴苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 以69.8%的产率得到(-)4-bromobenzoic acid, 1-(3,4-dimethoxyphenyl)-2-<4-(7-oxo-1,3,5-cycloheptatrien-1-yl)-1-piperazinyl>ethyl ester
  参考文献：
  名称：

  Troponoid. V. Crystallographic studies on AY-27110 — a dopamine agonist of the troponylpiperazine series

  摘要：

  通过X射线分析，确定了多巴胺激动剂2-[4-[2-羟基-2-(3′,4′-二甲基苯基)乙基]-1-哌嗪基]-2,4,6-环庚三烯-1-酮（AY-27110）的p-溴苯甲酰衍生物2的晶体结构和绝对构型。C28H29BrN2O5的晶体属于单斜晶系P21，a=12.553(2)Å，b=6.359(1)Å，c=17.575(3)Å，β=108.32(1)°，V=1331.81Å3，Z=2，ρc=1.380，ρo=1.384 g cm-3。对于2155个观察到的反射，最终R为0.036，R(w)为0.039。通过18个对应Friedel对的反射强度显著差异，证明该对映体的手性为S(−)。哌嗪环具有扭曲的椅子形式，在最靠近环庚三烯环的N原子处被压扁，类似于精神活性剂氯硝西泮和阿莫西泮。

  DOI：

  10.1139/v82-386
• 作为产物：
  描述：

  2-(1-piperazinyl)-2,4,6-cycloheptatrien-1-one methanesulfonic acid salt 在 sodium tetrahydroborate 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 26.0h， 生成 西拉多巴
  参考文献：
  名称：

  Troponoids. 7. Chemistry and dopamine agaonist activity of ciladopa and related aralkyltroponylpiperazines

  摘要：

  A series of N-aralkyltroponylpiperazine derivatives were synthesized and evaluated for dopaminergic activity in rats rendered hypokinetic by the bilateral injection of 6-hydroxydopamine (6-OHDA) into the anterolateral hypothalamus. Several members of the series were active, and a structure-activity relationship is presented. A few selected compounds were also evaluated with regard to their ability to induce contralateral rotational behavior in rats with a unilateral 6-OHDA-induced lesion of the nigrostriatal dopamine (DA) pathway and to suppress elevated serum prolactin levels. The compounds were compared to bromocriptine. Some of the more potent analogues were also assayed for their binding affinity to dopamine (DA) and alpha 1-adrenergic receptors. The results established that the potency of some of the compounds were comparable or superior to that of bromocriptine indicated that potent dopaminergic activity was dependent on the presence of both a substituted phenyl and a troponylpiperazine moiety, and confirmed that the dopaminergic activity depends on relative and absolute stereochemistry.

  DOI：

  10.1021/jm00152a004

文献信息

• [EN] TREATMENT OF AUTISM SPECTRUM DISORDERS, OBSESSIVE-COMPULSIVE DISORDER AND ANXIETY DISORDERS<br/>[FR] TRAITEMENT DE TROUBLES DU SPECTRE AUTISTIQUE, DE TROUBLES OBSESSIVO-COMPULSIFS ET DE TROUBLES DE L'ANXIÉTÉ
  申请人：RUGEN HOLDINGS CAYMAN LTD

  公开号：WO2018098128A1

  公开（公告）日：2018-05-31

  Disclosed are methods for treating NMDA receptor-mediated disorders by administering certain NR2B subunit-selective NMDA (N methyl-D aspartate) antagonists. NMDA receptor-mediated disorders include autism spectrum disorders, obsessive-compulsive disorder and anxiety disorders.

  揭示了通过给予特定NR2B亚单位选择性NMDA（N-甲基-D-天冬氨酸）拮抗剂来治疗NMDA受体介导的疾病的方法。NMDA受体介导的疾病包括自闭症谱系障碍、强迫症和焦虑症。
• [EN] TREATMENT OF ANXIETY DISORDERS AND AUTISM SPECTRUM DISORDERS<br/>[FR] TRAITEMENT DES TROUBLES DE L'ANXIÉTÉ ET DES TROUBLES DU SPECTRE AUTISTIQUE
  申请人：RUGEN HOLDINGS CAYMAN LTD

  公开号：WO2016049048A1

  公开（公告）日：2016-03-31

  Disclosed are methods for treating autism spectrum disorders and/or anxiety disorders by administering certain NR2B subunit-selective NMDA (N methyl-D aspartate) antagonists. Anxiety disorders include agoraphobia (with or without panic disorder), generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder (PD), post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD).

  本文披露了通过给予特定NR2B亚单位选择性NMDA（N-甲基-D-天冬氨酸）拮抗剂来治疗自闭症谱系障碍和/或焦虑障碍的方法。焦虑障碍包括广场恐惧症（伴有或不伴有惊恐障碍）、广泛性焦虑障碍（GAD）、社交焦虑障碍（SAD）、惊恐障碍（PD）、创伤后应激障碍（PTSD）和强迫症（OCD）。
• [EN] 3,3-DIFLUOROPIPERIDINE CARBAMATE HETEROCYCLIC COMPOUNDS AS NR2B NMDA RECEPTOR ANTAGONISTS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES 3,3-DIFLUOROPIPÉRIDINE CARBAMATE UTILISÉS EN TANT QU'ANTAGONISTES DES RÉCEPTEURS NMDA NR2B
  申请人：RUGEN HOLDINGS (CAYMAN) LTD

  公开号：WO2016196513A1

  公开（公告）日：2016-12-08

  Disclosed are chemical entities of Formula (I), wherein R1 and Z are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of Formula (I), and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of Formula (I).

  本文披露了化学实体的化学式（I），其中R1和Z如本文所定义，作为NR2B亚型选择性受体拮抗剂。还披露了包括化学实体的化学式（I）的药物组合物，以及通过给予化学实体的化学式（I）来治疗与NR2B拮抗作用相关的各种疾病和疾病的方法，例如中枢神经系统疾病和疾病，如抑郁症。
• [EN] CARBONATE PRODRUGS AND METHODS OF USING THE SAME<br/>[FR] PROMÉDICAMENTS CARBONATÉS ET LEURS MÉTHODES D'UTILISATION
  申请人：NEUROGESX INC

  公开号：WO2009143297A1

  公开（公告）日：2009-11-26

  The present invention provides carbonate prodrugs which comprise a carbonic phosphoric anhydride prodrug moiety attached to the hydroxyl or carboxyl group of a parent drug moiety. The prodrugs may provide improved physicochemical properties over the parent drug. Also provided are methods of treating a disease or condition that is responsive to the parent drug using the carbonate prodrugs, as well as kits and unit dosages.

  本发明提供了碳酸盐前药，其包括连接到母药基团的羟基或羧基上的碳酸磷酸酐前药基团。这些前药可能比母药具有改进的物理化学性质。还提供了使用碳酸盐前药治疗对母药具有响应的疾病或症状的方法，以及配套工具和单剂量。
• [EN] SUBSTITUTED HETEROCYCLIC COMPOUNDS AS ALLOSTERIC MODULATORS OF GROUP II METABOTROPIC GLUTAMATE RECEPTORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES SUBSTITUÉS UTILISÉS COMME MODULATEURS ALLOSTÉRIQUES DE RÉCEPTEURS MÉTABOTROPIQUES DU GLUTAMATE DU GROUPE II
  申请人：MAVALON THERAPEUTICS LTD

  公开号：WO2018206820A1

  公开（公告）日：2018-11-15

  The present invention provides novel heterocyclic compounds of the general formula (I), including novel compounds of formula (la), and pharmaceutical compositions containing them. Moreover, the compounds of formula (I) or (la) and the pharmaceutical compositions containing them are provided for use in the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals. The compounds of formula (I) or (la) can act as modulators of nervous system receptors sensitive to glutamate, in particular as modulators of metabotropic glutamate receptors (mGluRs), which makes them particularly suitable for the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders. The present invention further provides compounds of formula (I) or (la) that are modulators of metabotropic glutamate receptors (mGluRs), particularly positive allosteric modulators of mG!uRs, and more specifically positive allosteric modulators of mGluR3.

  本发明提供了一般式(I)的新颖杂环化合物，包括一般式(la)的新化合物，以及含有它们的药物组合物。此外，提供了一般式(I)或(la)的化合物和含有它们的药物组合物，用于治疗和/或预防与改变谷氨酸能信号和/或功能相关的疾病，以及那些可能受到哺乳动物谷氨酸水平或信号改变影响的疾病。一般式(I)或(la)的化合物可以作为对谷氨酸敏感的神经系统受体的调节剂，特别是代谢型谷氨酸受体(mGluRs)的调节剂，这使它们特别适用于治疗和/或预防急性和慢性神经和/或精神障碍。本发明还提供了一般式(I)或(la)的化合物，它们是代谢型谷氨酸受体(mGluRs)的调节剂，特别是mGluRs的正向变构调节剂，更具体地说是mGluR3的正向变构调节剂。