2-Chloro-5-((S)-1-methyl-azetidin-2-ylmethoxy)-pyridine | 203564-55-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-Chloro-5-((S)-1-methyl-azetidin-2-ylmethoxy)-pyridine
• 英文别名: 2-chloro-5-[[(2S)-1-methylazetidin-2-yl]methoxy]pyridine
• CAS: 203564-55-0
• 化学式: C₁₀H₁₃ClN₂O
• 分子量: 212.679
• InChiKey: XWJYFOCRQNJGJO-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  25.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氯-5-羟基吡啶 在 盐酸 、 sodium cyanoborohydride 、 溶剂黄146 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 4.5h， 生成 2-Chloro-5-((S)-1-methyl-azetidin-2-ylmethoxy)-pyridine
  参考文献：
  名称：

  Identification and Initial Structure−Activity Relationships of (R)-5-(2-Azetidinylmethoxy)-2-chloropyridine (ABT-594), a Potent, Orally Active, Non-Opiate Analgesic Agent Acting via Neuronal Nicotinic Acetylcholine Receptors

  摘要：

  New members of a previously reported series of 3-pyridyl ether compounds are disclosed as novel, potent analgesic agents acting through neuronal nicotinic acetylcholine receptors. Both (R)-2-chloro-5-(2-azetidinylmethoxy)pyridine (ABT-594, 5) and its S-enantiomer (4) show potent analgesic activity in the mouse hot-plate assay following either intraperitoneal (ip) or oral (po) administration, as well as activity in the mouse abdominal constriction (writhing) assay, a model of persistent pain. Compared to the S-enantiomer and to the prototypical potent nicotinic analgesic agent (+/-)-epibatidine, 5 shows diminished activity in models of peripheral side effects. Structure-activity studies of analogues related to 4 and 5 suggest that the N-unsubstituted azetidine moiety and the 2-chloro substituent on the pyridine ring are important contributors to potent analgesic activity.

  DOI：

  10.1021/jm9706224

文献信息

• NOVEL ANALGESIC AGENTS
  申请人：Advanced Medicine, Inc.

  公开号：EP1083917A1

  公开（公告）日：2001-03-21
• US5948793A
  申请人：——

  公开号：US5948793A

  公开（公告）日：1999-09-07
• US6288055B1
  申请人：——

  公开号：US6288055B1

  公开（公告）日：2001-09-11
• [EN] NOVEL ANALGESIC AGENTS<br/>[FR] NOUVEAUX AGENTS ANALGESIQUES
  申请人：ADVANCED MEDICINE INC

  公开号：WO1999064038A1

  公开（公告）日：1999-12-16

  Novel multibinding compounds are disclosed. The compounds of the invention comprise from 2-10 ligands covalently connected, each of said ligands being capable of binding to an nAChR receptor, thereby modulating the biological processes/functions thereof.
• Identification and Initial Structure−Activity Relationships of (<i>R</i>)-5-(2-Azetidinylmethoxy)-2-chloropyridine (ABT-594), a Potent, Orally Active, Non-Opiate Analgesic Agent Acting via Neuronal Nicotinic Acetylcholine Receptors
  作者：Mark W. Holladay、James T. Wasicak、Nan-Horng Lin、Yun He、Keith B. Ryther、Anthony W. Bannon、Michael J. Buckley、David J. B. Kim、Michael W. Decker、David J. Anderson、Jeffrey E. Campbell、Theresa A. Kuntzweiler、Diana L. Donnelly-Roberts、Marietta Piattoni-Kaplan、Clark A. Briggs、Michael Williams、Stephen P. Arneric

  DOI：10.1021/jm9706224

  日期：1998.2.1

  New members of a previously reported series of 3-pyridyl ether compounds are disclosed as novel, potent analgesic agents acting through neuronal nicotinic acetylcholine receptors. Both (R)-2-chloro-5-(2-azetidinylmethoxy)pyridine (ABT-594, 5) and its S-enantiomer (4) show potent analgesic activity in the mouse hot-plate assay following either intraperitoneal (ip) or oral (po) administration, as well as activity in the mouse abdominal constriction (writhing) assay, a model of persistent pain. Compared to the S-enantiomer and to the prototypical potent nicotinic analgesic agent (+/-)-epibatidine, 5 shows diminished activity in models of peripheral side effects. Structure-activity studies of analogues related to 4 and 5 suggest that the N-unsubstituted azetidine moiety and the 2-chloro substituent on the pyridine ring are important contributors to potent analgesic activity.