(S)-2-(pyridin-3-yloxymethyl)pyrrolidine-1-carboxylic acid tert-butyl ester | 161417-33-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (S)-2-(pyridin-3-yloxymethyl)pyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: 2-(pyridin-3-yl-oxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester；3-((1-t-butoxycarbonyl-2-(S)-pyrrolidinyl)methoxy)pyridine；tert-butyl (2S)-2-(pyridin-3-yloxymethyl)pyrrolidine-1-carboxylate
• CAS: 161417-33-0
• 化学式: C₁₅H₂₂N₂O₃
• 分子量: 278.351
• InChiKey: XCAOIXZWOMOOBJ-LBPRGKRZSA-N

物化性质

• 沸点：
  390.6±12.0 °C(Predicted)
• 密度：
  1.114±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  51.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-(pyridin-3-yloxymethyl)pyrrolidine-1-carboxylic acid tert-butyl ester 在 四丁基氟化铵 、 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.25h， 生成 1-(4-hydroxy-benzyl)-5-[2-(pyridin-3-yl-oxymethyl)-pyrrolidine-1-sulfonyl]-1H-indole-2,3-dione
  参考文献：
  名称：

  Isatin Sulfonamide Analogs Containing a Michael Addition Acceptor:  A New Class of Caspase 3/7 Inhibitors

  摘要：

  A series of isatin sulfonamide analogs having a Michael acceptor were prepared and their potencies for inhibiting caspase-1, -3, -6, -7, and -8 were evaluated. These compounds have nanomolar potency for inhibiting the executioner caspases, caspase-3 and caspase-7, and have a low potency for inhibiting caspase-1, caspase-6, and caspase-8. The inhibition mechanism was investigated through NMR studies of the reaction between 11d and benzylmercaptan as a model for Cys-285 in the active site of caspase-3.

  DOI：

  10.1021/jm070506t
• 作为产物：
  描述：

  N-Boc-L-脯氨醇 在 吡啶 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 24.67h， 生成 (S)-2-(pyridin-3-yloxymethyl)pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  N-Benzylisatin Sulfonamide Analogues as Potent Caspase-3 Inhibitors:  Synthesis, in Vitro Activity, and Molecular Modeling Studies

  摘要：

  A number of isatin sulfonamide analogues were prepared and their potencies for inhibiting caspase-1, -3, -6, -7, and -8 were evaluated in vitro. Several compounds displaying a nanomolar potency for inhibiting the executioner caspases, caspase-3 and caspase-7, were identified. These compounds were also observed to have a low potency for inhibiting the initiator caspases, caspase-1 and caspase-8, and caspase-6. Molecular modeling studies provided further insight into the interaction of this class of compounds with activated caspase-3. The results of the current study revealed a number of non-peptide-based caspase inhibitors that may be useful in assessing the role of inhibiting the executioner caspases in minimizing tissue damage in disease conditions characterized by unregulated apoptosis.

  DOI：

  10.1021/jm0506625

文献信息

• NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS AND THE USES THEREOF
  申请人：Chandrasekhar Jayaraman

  公开号：US20130184313A1

  公开（公告）日：2013-07-18

  The invention relates to pyridinyl nicotinic acetylcholine receptor ligands, compositions comprising an effective amount of a pyridinyl nicotinic acetylcholine receptor ligand and methods to treat or prevent a condition, such as depression and nicotine dependence, comprising administering to an animal in need thereof an effective amount of a pyridinyl nicotinic acetylcholine receptor ligand.

  该发明涉及吡啶基烟碱乙酰胆碱受体配体，包含有效量吡啶基烟碱乙酰胆碱受体配体的组合物，以及治疗或预防某种疾病的方法，如抑郁症和尼古丁依赖症，包括向需要的动物施用有效量吡啶基烟碱乙酰胆碱受体配体。
• Novel 3-Pyridyl Ethers with Subnanomolar Affinity for Central Neuronal Nicotinic Acetylcholine Receptors
  作者：Melwyn A. Abreo、Nan-Horng Lin、David S. Garvey、David E. Gunn、Ann-Marie Hettinger、James T. Wasicak、Patricia A. Pavlik、Yvonne C. Martin、Diana L. Donnelly-Roberts、David J. Anderson、James P. Sullivan、Michael Williams、Stephen P. Arneric、Mark W. Holladay

  DOI：10.1021/jm9506884

  日期：1996.1.1

  disorders as well as the diversity of brain neuronal nicotine acetylcholine receptors (nAChRs) have suggested an opportunity to develop subtype-selective nAChR ligands for the treatment of specific CNS disorders with reduced side effect liabilities. We report a novel series of 3-pyridyl ether compounds which possess subnanomolar affinity for brain nAChRs and differentially activate subtypes of neuronal nAChRs

  最近的证据表明胆碱能通道调节剂具有治疗中枢神经系统（CNS）疾病的治疗潜力以及脑神经元烟碱乙酰胆碱受体（nAChRs）的多样性，这表明有机会开发亚型选择性nAChR配体来治疗中枢神经系统疾病。减少副作用的特定中枢神经系统疾病。我们报告了一系列新型的3-吡啶醚化合物，对大脑nAChRs具有亚纳摩尔的亲和力，并差异性激活神经元nAChRs的亚型。描述了该系列主要成员的合成与构效关系，包括A-85380（4a），它对大鼠脑[（3）H]-（-）-胱氨酸结合位点和与尼古丁相比，对人alpha4beta2 nAChR亚型刺激离子通量的功效为163％，和A-84543（2a），与人类神经节型nAChRs相比，在刺激人alpha4beta2 nAchR亚型的离子通量方面显示出84倍的选择性。计算研究表明，可以实现4A的低能量构象异构体与（S）-尼古丁和（-）-依巴替丁的合理叠加。
• [EN] HETEROCYCLIC ETHER AND THIOETHER COMPOUNDS USEFUL IN CONTROLLING CHEMICAL SYNAPTIC TRANSMISSION<br/>[FR] COMPOSES ETHER ET THIOETHER HETEROCYCLIQUES UTILISES DANS LA REGULATION DE LA TRANSMISSION SYNAPTIQUE CHIMIQUE
  申请人：ABBOTT LABORATORIES

  公开号：WO1999032480A1

  公开（公告）日：1999-07-01

  (EN) Novel compounds having formulas (I), (II) or (III) or pharmaceutically-acceptable salts or prodrugs thereof, which are useful for controlling synaptic transmission; to therapeutically-effective pharmaceutical compositions of these compounds; and to the use of said compositions to controlling synaptic transmission in human or veterinary patients.(FR) L'invention porte sur de nouveaux composés ayant les formules (I), (II) ou (III), ou sur leurs sels pharmaceutiquement acceptables ou promédicaments, et qui sont utilisés dans la régulation de la transmission synaptique. L'invention porte également sur les compositions pharmaceutiques thérapeutiquement efficaces de ces composés, et sur l'utilisation de ces compositions pour réguler la transmission synaptique chez l'homme ou l'animal.

  （中文翻译）本发明涉及具有公式（I），（II）或（III）或其药学上可接受的盐或前药的新化合物，其用于控制突触传递；以及这些化合物的治疗有效的药物组合物，以及使用该组合物在人类或兽医患者中控制突触传递的用途。
• 3-pyridyloxymethyl heterocyclic ether compounds useful in controlling
  申请人：Abbott Laboratories

  公开号：US05948793A1

  公开（公告）日：1999-09-07

  Novel heterocyclic ether compounds of the formula: ##STR1## wherein n, *, R.sup.1, R.sup.2, R.sup.3 and y are specifically defined, or pharmaceutically acceptable salts or prodrugs thereof, which are useful in selectively controlling neurotransmitter release; therapeutically-effective pharmaceutical compositions of these compounds; and use of said compositions to selectively control neurotransmitter release in mammals.

  该专利涉及一种新型杂环醚化合物，其化学式为：##STR1## 其中n，*，R.sup.1，R.sup.2，R.sup.3和y都有具体定义，或其药学上可接受的盐或前药。这些化合物可用于选择性控制神经递质释放，并制备了具有治疗效果的药物组合物。该专利还涉及将上述组合物用于选择性控制哺乳动物神经递质释放的方法。
• Synthesis and structure-activity relationships of pyridine-modified analogs of 3-[2-((S)-pyrrolidinyl)methoxy]pyridine, A-84543, a potent nicotinic acetylcholine receptor agonist
  作者：Nan-Horng Lin、David E Gunn、Yihong Li、Yun He、Hao Bai、Keith B Ryther、Theresa Kuntzweiler、Diana L Donnelly-Roberts、David J Anderson、Jeffrey E Campbell、James P Sullivan、Stephen P Arneric、Mark W Holladay

  DOI：10.1016/s0960-894x(98)00019-5

  日期：1998.2

  Analogs of 3-[2-((S)-pyrrolidinyl)methoxy]pyridine (A-84543, 1) with 2-, 4-, 5-, and 6-substituents on the pyridine ring were synthesized. These analogs exhibited Ki values ranging from 0.15 to > 9,000 nM when tested in vitro for neuronal nicotinic acetylcholine receptor binding activity. Assessment of functional activity at subtypes of neuronal nicotinic acetylcholine receptors indicates that pyridine substitution can have a profound effect on efficacy at these subtypes, and several subtype-selective agonists and antagonists have been identified. (C) 1998 Elsevier Science Ltd. All rights reserved.