3-[4-(3-Phenyl-propylsulfanyl)-[1,2,5]thiadiazol-3-yl]-pyridine | 169542-77-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 3-[4-(3-Phenyl-propylsulfanyl)-[1,2,5]thiadiazol-3-yl]-pyridine
• 英文别名: 3-(3-phenylpropylsulfanyl)-4-pyridin-3-yl-1,2,5-thiadiazole
• CAS: 169542-77-2
• 化学式: C₁₆H₁₅N₃S₂
• 分子量: 313.447
• InChiKey: OZQIXBHDKPYMDC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  92.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[4-(3-Phenyl-propylsulfanyl)-[1,2,5]thiadiazol-3-yl]-pyridine 在 sodium tetrahydroborate 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 21.0h， 生成 3-(3-(3-Phenylpropylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine
  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
• 作为产物：
  描述：

  3-氯-4-(吡啶-3-基)-1,2,5-噻二唑 在 sodium hydrogensulfide 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-[4-(3-Phenyl-propylsulfanyl)-[1,2,5]thiadiazol-3-yl]-pyridine
  参考文献：
  名称：

  Identification of side chains on 1,2,5-thiadiazole-azacycles optimal for muscarinic M1 receptor activation

  摘要：

  Series of analogs to the functional mi selective agonist, xanomeline (hexyloxy-TZTP), were evaluated for their in vitro ml efficacy in cell lines transfected with the human ml receptor. Systematic variation of the side chain and the azacyclic ring led to the discovery of potent muscarinic agonists with robust ml efficacy, ail having the phenylpropargyloxy/thio as the side chain. The most selective compound was the phenylpropargylthio-[3.2.1] endo analog 28, which is a potent and efficacious mi agonist with no m2 activity. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00509-5

文献信息

• Identification of side chains on 1,2,5-thiadiazole-azacycles optimal for muscarinic M1 receptor activation
  作者：Per Sauerberg、Lone Jeppesen、Preben H Olesen、Malcolm J Sheardown、Anders Fink-Jensen、Thøger Rasmussen、Karin Rimvall、Harlan E Shannon、Frank P Bymaster、Neil W DeLapp、Dave O Calligaro、John S Ward、Celia A Whitesitt、Christian Thomsen

  DOI：10.1016/s0960-894x(98)00509-5

  日期：1998.10

  Series of analogs to the functional mi selective agonist, xanomeline (hexyloxy-TZTP), were evaluated for their in vitro ml efficacy in cell lines transfected with the human ml receptor. Systematic variation of the side chain and the azacyclic ring led to the discovery of potent muscarinic agonists with robust ml efficacy, ail having the phenylpropargyloxy/thio as the side chain. The most selective compound was the phenylpropargylthio-[3.2.1] endo analog 28, which is a potent and efficacious mi agonist with no m2 activity. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Muscarinic Analgesics with Potent and Selective Effects on the Gastrointestinal Tract:  Potential Application for the Treatment of Irritable Bowel Syndrome
  作者：Charles H. Mitch、Thomas J. Brown、Frank P. Bymaster、David O. Calligaro、Donna Dieckman、Leander Merrit、Steven C. Peters、Steven J. Quimby、Harlan E. Shannon、Lisa A. Shipley、John S. Ward、Kristian Hansen、Preben H. Olesen、Per Sauerberg、Malcolm J. Sheardown、Michael D. B. Swedberg、Peter Suzdak、Beverley Greenwood

  DOI：10.1021/jm9602470

  日期：1997.2.1

  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.