(3S)-3-[4-(丁基硫基)-1,2,5-噻二唑-3-基]奎宁环 | 141575-50-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 中文名称: (3S)-3-[4-(丁基硫基)-1,2,5-噻二唑-3-基]奎宁环
• 英文名称: LY297802/NNC11-1053
• 英文别名: (+)-Vedaclidine；(S)-3-(4-(Butylthio)-1,2,5-thiadiazol-3-yl)quinuclidine；3-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-4-butylsulfanyl-1,2,5-thiadiazole
• CAS: 141575-50-0
• 化学式: C₁₃H₂₁N₃S₂
• 分子量: 283.462
• InChiKey: WZZPXVURFDJHGI-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  82.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-奎宁环酮盐酸盐 在 palladium on activated charcoal 、 5% Pd on active carbon 二氯化二硫 、 sodium hydrogensulfide 、 氢气 、 sodium methylate 、 sodium ethanolate 、 potassium carbonate 、 三乙胺 、 亚硝酸异戊酯 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0~80.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 生成 (3S)-3-[4-(丁基硫基)-1,2,5-噻二唑-3-基]奎宁环
  参考文献：
  名称：

  Muscarinic Analgesics with Potent and Selective Effects on the Gastrointestinal Tract:  Potential Application for the Treatment of Irritable Bowel Syndrome

  摘要：

  Irritable bowel syndrome (IBS) is a pathopysiolocal condition characterized by abnormal bowel habits that are frequently accompanied by abdominal pain. Current therapy based on reducing high-amplitude GI contractions with nonselective muscarinic antagonists is limited in efficacy due to typical muscarinic side effects and provides no pain relief. We have previously found potent antinociceptive agents acting through muscarinic receptors. In the present work, new 1,2,5-thiadiazole-based structures with muscarinic activity have been evaluated both for activity as analgesics in the mouse withing assay and for activity in normalizing spontaneous cluster contractions in ferret jejunum as a model of IBS in humans. (5R,6R)-exo-6-[4-[(4,4,4-Trifluorobutyl)thio]-1,2,5-thiadiazol-3-yl]-1-azabicyclo[3.2.1]octane (35, LY316108/NNC11-2192) was found to offer an exceptional profile combining analgesic potency in mouse writhing (ED(50) = 0.1 mg/kg) along with potency for normalization of GI motility (ED(50) = 0.17 mg/kg). This combination of GI and analgesic potency suggests 35 as an excellent candidate for evaluation as a potential treatment of IBS.

  DOI：

  10.1021/jm9602470

文献信息

• METHODS AND COMPOSITIONS FOR TREATMENT OF DISORDERS AMELIORATED BY MUSCARINIC RECEPTOR ACTIVATION
  申请人：Puretech Ventures

  公开号：EP3061821A1

  公开（公告）日：2016-08-31

  Methods for the treatment of CNS disorders using combinations of muscarinic activators and inhibitors, and medicaments comprising muscarinic activators and inhibitors.

  使用毒蕈碱激活剂和抑制剂组合治疗中枢神经系统疾病的方法，以及包含毒蕈碱激活剂和抑制剂的药物。
• NICOTINIC CHANNEL SUBUNITS OF POLLINATOR INSECTS AND THEIR USES THEREOF
  申请人：Centre National de la Recherche Scientifique (C.N.R.S.)

  公开号：EP3118219A1

  公开（公告）日：2017-01-18

  The present invention relates to the cloning of the nicotinic acetylcholine receptors (nAChR) subunits in species from the phylum arthropoda and in particular a pollinator insect such as Apis mellifera and their uses thereof.

  本发明涉及节肢动物门物种，特别是授粉昆虫（如蜜蜂）中烟碱乙酰胆碱受体（nAChR）亚基的克隆及其用途。
• Compositions and methods for enhancing odorant receptor activity
  申请人：Duke University

  公开号：US10072292B2

  公开（公告）日：2018-09-11

  The present invention relates to polypeptides capable of modulating odorant receptor activation. In particular, the present invention provides polypeptides (e.g., type 3 muscarinic actetylcholine receptor M3) capable of enhancing odorant receptor activation. The present invention further provides assays for the detection of ligands specific for various odorant receptors. Additionally, the present invention provides methods of screening for polypeptide polymorphisms and mutations associated with odorant receptor activation (e.g., polymorphisms and mutations associated with muscarinic actetylcholine receptor polypeptides (e.g., M1, M2, M3, M4, M5)), as well as methods of screening for therapeutic agents, ligands, and modulators of such proteins.

  本发明涉及能够调节气味受体活化的多肽。特别是，本发明提供了能够增强气味受体活化的多肽（如 3 型毒蕈碱动乙酰胆碱受体 M3）。本发明进一步提供了检测各种气味受体特异性配体的检测方法。此外，本发明还提供了筛选与气味受体激活相关的多肽多态性和突变的方法（例如，与毒蕈碱动乙酰胆碱受体多肽（例如，M1、M2、M3、M4、M5）相关的多态性和突变），以及筛选此类蛋白质的治疗剂、配体和调节剂的方法。
• Methods and compositions for treatment of disorders ameliorated by muscarinic receptor activation
  申请人：PureTech Health LLC

  公开号：US10238643B2

  公开（公告）日：2019-03-26

  Methods for the treatment of CNS disorders using combinations of muscarinic activators and inhibitors, and medicaments comprising muscarinic activators and inhibitors.

  使用毒蕈碱激活剂和抑制剂组合治疗中枢神经系统疾病的方法，以及包含毒蕈碱激活剂和抑制剂的药物。
• Methods and compositions for treating cancer using P2RX2 inhibitors
  申请人：Flagship Pioneering Innovations V, Inc.

  公开号：US10457740B1

  公开（公告）日：2019-10-29

  The present invention provides methods for treating cancer using P2RX2 inhibitors, such as P2RX2 inhibitory antibodies, among others. The invention also features compositions containing P2RX2 inhibitors, methods of diagnosing patients with P2RX2-associated cancer, and methods of predicting the response of cancer in a subject to treatment with P2RX2 inhibitors.

  本发明提供了使用 P2RX2 抑制剂（如 P2RX2 抑制抗体等）治疗癌症的方法。本发明还包括含有 P2RX2 抑制剂的组合物、诊断 P2RX2 相关癌症患者的方法以及预测癌症对 P2RX2 抑制剂治疗的反应的方法。