(+)-5,6,7,8-tetrahydrospiro[cyclohepta[b]pyridine-9,2'-[1,3]dioxolan]-7-ylmethyl 4-methylbenzenesulfonate | 1039359-02-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (+)-5,6,7,8-tetrahydrospiro[cyclohepta[b]pyridine-9,2'-[1,3]dioxolan]-7-ylmethyl 4-methylbenzenesulfonate
• 英文别名: [(7'R)-spiro[1,3-dioxolane-2,9'-5,6,7,8-tetrahydrocyclohepta[b]pyridine]-7'-yl]methyl 4-methylbenzenesulfonate
• CAS: 1039359-02-8
• 化学式: C₂₀H₂₃NO₅S
• 分子量: 389.472
• InChiKey: TYNWGJJJGZDFSJ-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  83.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(2,6-二氯苯基)哌啶 、 (+)-5,6,7,8-tetrahydrospiro[cyclohepta[b]pyridine-9,2'-[1,3]dioxolan]-7-ylmethyl 4-methylbenzenesulfonate 在 三乙胺 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  A Novel Class of Cycloalkano[b]pyridines as Potent and Orally Active Opioid Receptor-like 1 Antagonists with Minimal Binding Affinity to the hERG K⁺Channel

  摘要：

  A series of compounds based on 7-{[4-(2-methylphenyl)piperidin-1-yl]methyl}-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-9-ol ((-)-8b), a potent and selective opioid receptor-like 1 (ORL1) antagonist, was prepared and evaluated using structure-activity relationship studies with the aim of removing its affinity to human ether-a-go-go related gene (hERG) K+ channel. From these studies, 10l was identified as an optimized structure with respect to ORL1 antagonist activity, and affinity to the hERG K+ channel. Furthermore, 10l showed good in vivo antagonism with a wide therapeutic index in regards to adverse cardiovascular effects.

  DOI：

  10.1021/jm701590h
• 作为产物：
  描述：

  、 对甲苯磺酰氯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 (+)-5,6,7,8-tetrahydrospiro[cyclohepta[b]pyridine-9,2'-[1,3]dioxolan]-7-ylmethyl 4-methylbenzenesulfonate 、 (-)-5,6,7,8-tetrahydrospiro[cyclohepta[b]pyridine-9,2'-[1,3]dioxolan]-7-ylmethyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  A Novel Class of Cycloalkano[b]pyridines as Potent and Orally Active Opioid Receptor-like 1 Antagonists with Minimal Binding Affinity to the hERG K⁺Channel

  摘要：

  A series of compounds based on 7-{[4-(2-methylphenyl)piperidin-1-yl]methyl}-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-9-ol ((-)-8b), a potent and selective opioid receptor-like 1 (ORL1) antagonist, was prepared and evaluated using structure-activity relationship studies with the aim of removing its affinity to human ether-a-go-go related gene (hERG) K+ channel. From these studies, 10l was identified as an optimized structure with respect to ORL1 antagonist activity, and affinity to the hERG K+ channel. Furthermore, 10l showed good in vivo antagonism with a wide therapeutic index in regards to adverse cardiovascular effects.

  DOI：

  10.1021/jm701590h

文献信息

• Cycloalkanopyridine derivative
  申请人：Takahashi Hirobumi

  公开号：US20070191419A1

  公开（公告）日：2007-08-16

  Provided are cycloalkanopyridine derivatives of formula [I]: [wherein the symbols are the same as those stated in the description]. The compounds act as a nociceptin receptor antagonist, and are useful as medicines for diseases associated with a nociceptin receptor, for example, as a reliever against tolerance to a narcotic analgesic; a reliever against dependence on or addiction to a narcotic analgesic; an analgesic enhancer; an antiobesitic or appetite suppressor; a treating or prophylactic agent for cognitive impairment and dementia/amnesia; an agent for treating developmental cognitive abnormality; a remedy for schizophrenia; an agent for treating neurodegenerative diseases; an anti-depressant or treating agent for affective disorder; a treating or prophylactic agent for diabetes insipidus; a treating or prophylactic agent for polyuria; or a remedy for hypotension.

  提供的是式[I]的环烷基吡啶衍生物：[其中符号与说明中所述相同]。这些化合物作为一种nociceptin受体拮抗剂，可用作与nociceptin受体相关的疾病的药物，例如作为缓解对麻醉镇痛剂的耐受性的药物；对麻醉镇痛剂的依赖或成瘾的缓解剂；镇痛增强剂；抗肥胖或食欲抑制剂；治疗或预防认知障碍和失忆症的药物；治疗发育性认知异常的药物；治疗精神分裂症的药物；治疗神经退行性疾病的药物；抗抑郁或治疗情感障碍的药物；治疗或预防尿崩症的药物；治疗或预防多尿症的药物；或治疗低血压的药物。
• CYCLOALKANOPYRIDINE DERIVATIVE
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP1726590A1

  公开（公告）日：2006-11-29

  Provided are cycloalkanopyridine derivatives of formula [I]: [wherein the symbols are the same as those stated in the description]. The compounds act as a nociceptin receptor antagonist, and are useful as medicines for diseases associated with a nociceptin receptor, for example, as a reliever against tolerance to a narcotic analgesic; a reliever against dependence on or addiction to a narcotic analgesic; an analgesic enhancer; an antiobesitic or appetite suppressor; a treating or prophylactic agent for cognitive impairment and dementia/amnesia; an agent for treating developmental cognitive abnormality; a remedy for schizophrenia; an agent for treating neurodegenerative diseases; an anti-depressant or treating agent for affective disorder; a treating or prophylactic agent for diabetes insipidus; a treating or prophylactic agent for polyuria; or a remedy for hypotension.

  所提供的是式[I]的环烷吡啶衍生物： [其中符号与描述中的符号相同]。这些化合物具有痛觉素受体拮抗剂的作用，可作为治疗与痛觉素受体相关疾病的药物，例如，可作为麻醉镇痛剂耐受性的缓解剂；麻醉镇痛剂依赖或成瘾的缓解剂；镇痛增强剂；抗厌食或食欲抑制剂；治疗或预防认知障碍和痴呆/失忆症的药物；治疗发育性认知异常的药物；治疗精神分裂症的药物；治疗神经退行性疾病的药物；抗抑郁剂或治疗情感障碍的药物；治疗或预防糖尿病性尿崩症的药物；治疗或预防多尿症的药物；或治疗低血压的药物。
• US7855294B2
  申请人：——

  公开号：US7855294B2

  公开（公告）日：2010-12-21
• A Novel Class of Cycloalkano[<i>b</i>]pyridines as Potent and Orally Active Opioid Receptor-like 1 Antagonists with Minimal Binding Affinity to the hERG K⁺Channel
  作者：Takashi Yoshizumi、Hirobumi Takahashi、Hiroshi Miyazoe、Yuichi Sugimoto、Tomohiro Tsujita、Tetsuya Kato、Hirokatsu Ito、Hiroshi Kawamoto、Mioko Hirayama、Daisuke Ichikawa、Tomoko Azuma-Kanoh、Satoshi Ozaki、Yoshihiro Shibata、Takeshi Tani、Masato Chiba、Yasuyuki Ishii、Shoki Okuda、Kiyoshi Tadano、Takahiro Fukuroda、Osamu Okamoto、Hisashi Ohta

  DOI：10.1021/jm701590h

  日期：2008.7

  A series of compounds based on 7-[4-(2-methylphenyl)piperidin-1-yl]methyl}-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-9-ol ((-)-8b), a potent and selective opioid receptor-like 1 (ORL1) antagonist, was prepared and evaluated using structure-activity relationship studies with the aim of removing its affinity to human ether-a-go-go related gene (hERG) K+ channel. From these studies, 10l was identified as an optimized structure with respect to ORL1 antagonist activity, and affinity to the hERG K+ channel. Furthermore, 10l showed good in vivo antagonism with a wide therapeutic index in regards to adverse cardiovascular effects.