(3aR,7aS)-2-<(R)-1-phenylethyl>-perhydropyrano<3,4-c>pyrrol-4-one | 134234-14-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (3aR,7aS)-2-<(R)-1-phenylethyl>-perhydropyrano<3,4-c>pyrrol-4-one
• 英文别名: (3aR,7aS)-2-[(1R)-1-phenylethyl]-1,3,3a,6,7,7a-hexahydropyrano[3,4-c]pyrrol-4-one
• CAS: 134234-14-3
• 化学式: C₁₅H₁₉NO₂
• 分子量: 245.321
• InChiKey: XNUPMFBUUQACBR-BNOWGMLFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (R)-1-苯基-N-((三甲基甲硅烷基)甲基)乙胺 在 三氟乙酸 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 4.0h， 生成 (3aR,7aS)-2-<(R)-1-phenylethyl>-perhydropyrano<3,4-c>pyrrol-4-one
  参考文献：
  名称：

  Cottrell, Ian F.; Hands, David; Kennedy, Derek J., Journal of the Chemical Society. Perkin transactions I, 1991, # 5, p. 1091 - 1097

  摘要：

  DOI：

文献信息

• Novel Antimuscarinic Antidepressant-like Compounds with Reduced Effects on Cognition
  作者：Chad R. Johnson、Brian D. Kangas、Emily M. Jutkiewicz、Gail Winger、Jack Bergman、Andrew Coop、James H. Woods

  DOI：10.1124/jpet.120.000337

  日期：2021.6

  The cholinergic nervous system has been implicated in mood disorders, evident in the fast-onset antidepressant effects of scopolamine, a potent muscarinic antagonist, in clinical studies. One prominent disadvantage of the use of scopolamine in the treatment of depression is its detrimental effects on cognition, especially as such effects might aggravate cognitive deficits that occur with depression itself. Thus, the identification of antimuscarinic drugs that are free of such detrimental effects may provide an important avenue for the development of novel therapeutics for the management of depression. The present data in rats indicate that a historical muscarinic antagonist, L-687,306, and a muscarinic antagonist of our own design, CJ2100, were as or more effective than scopolamine in antagonizing both the bradycardic effects of the muscarinic agonist arecoline in cardiovascular studies and its discriminative stimulus and rate-decreasing effects in behavioral studies. Additionally, both novel muscarinic antagonists were as effective as scopolamine in decreasing immobility in the forced swim test, a preclinical indicator of potential antidepressant activity. However, at equieffective or even larger doses, they were considerably less disruptive than scopolamine in assays of cognition-related behavior. All three drugs displayed high specificity for the mAChRs with few off-target binding sites, and CJ2100 showed modest affinity across the mAChRs when compared with L-687,306 and scopolamine. These data emphasize the dissimilar pharmacological profiles that are evident across antimuscarinic compounds and the potential utility of novel antagonists for the improved treatment of depression. SIGNIFICANCE STATEMENT Some clinical studies with the muscarinic antagonist scopolamine document its ability to produce antidepressant effects in patients with mood disorders; however, scopolamine also has well known adverse effects on both autonomic and centrally mediated physiological functions that limit its therapeutic use. This study characterizes the cardiovascular and discriminative stimulus effects of two novel muscarinic antagonists, L-687,306 and CJ2100, that produce antidepressant-like effects in a rodent model (forced swim test) without affecting touchscreen-based cognitive performance (titrating psychomotor vigilance and delayed matching-to-position).

  胆碱能神经系统与情绪障碍密切相关，这在临床研究中表现为阿托品（一种强效的毒蕈碱拮抗剂）快速起效的抗抑郁作用。使用阿托品治疗抑郁症的一个显著缺点是对认知的负面影响，尤其是这些影响可能加剧抑郁症本身所导致的认知缺陷。因此，识别不具有这些有害影响的抗毒蕈碱药物可能为开发新型治疗抑郁症的药物提供重要途径。目前在大鼠中的数据表明，历史上已知的毒蕈碱拮抗剂L-687,306，以及我们自行设计的毒蕈碱拮抗剂CJ2100，在抵消心血管研究中毒蕈碱受体激动剂阿瑞可林的心动过缓效应以及在行为研究中的分辨刺激和降低速率效果方面，效果与阿托品相当或更为显著。此外，这两种新型毒蕈碱拮抗剂在强迫游泳试验中减少无动性的效果与阿托品相当，该试验是潜在抗抑郁活性的前临床指示。然而，在等效或更高剂量下，它们在认知相关行为的测量中对行为的干扰程度明显低于阿托品。这三种药物对mAChRs显示出高度特异性，几乎没有偏离靶点的结合位点，并且与L-687,306和阿托品相比，CJ2100在mAChRs上显示出适度的亲和力。这些数据强调了不同的抗毒蕈碱化合物之间明显不同的药理特征，以及新型拮抗剂在改善抑郁症治疗中的潜在用途。 重要声明：一些与毒蕈碱拮抗剂阿托品相关的临床研究记录了其在情绪障碍患者中产生抗抑郁效果的能力；然而，阿托品对自主神经及中枢介导的生理功能的负面影响是众所周知的，这限制了其治疗用途。本研究描述了两种新型毒蕈碱拮抗剂L-687,306和CJ2100的心血管和分辨刺激效果，这两者在啮齿动物模型（强迫游泳试验）中产生类似抗抑郁的效果，同时没有影响基于触摸屏的认知表现（逐级心理运动警觉性和延迟匹配位置）。
• Chiral synthesis for producing 1-azabicyclo[2.2.1]heptane-3-carboxylates
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0398616A2

  公开（公告）日：1990-11-22

  A process for preparing substantially pure enantiomers of formula (I) where the * represents a chiral centre, x is 0 or 1, in exo-, endo- or a mixture of exo- and endo- forms; and R is hydrogen, alkyl or aralkyl, via diastereomers of formula (IIA) or (IIB):

  一种制备基本纯的式（I）对映体的工艺 其中 * 代表手性中心，x 为 0 或 1，外型、内型或外型与内型的混合物；R 为氢、烷基或芳烷基，通过式（IIA）或（IIB）的非对映体：
• US5104989A
  申请人：——

  公开号：US5104989A

  公开（公告）日：1992-04-14
• US5310911A
  申请人：——

  公开号：US5310911A

  公开（公告）日：1994-05-10
• Cottrell, Ian F.; Hands, David; Kennedy, Derek J., Journal of the Chemical Society. Perkin transactions I, 1991, # 5, p. 1091 - 1097
  作者：Cottrell, Ian F.、Hands, David、Kennedy, Derek J.、Paul, Kerensa J.、Wright, Stanley H. B.、Hoogsteen, Karst

  DOI：——

  日期：——