4-phenyl-4-(1-piperidinyl)cyclohexanone, ethylene ketal hydrochloride | 65620-12-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-phenyl-4-(1-piperidinyl)cyclohexanone, ethylene ketal hydrochloride
• 英文别名: 1-(8-Phenyl-1,4-dioxaspiro[4.5]decan-8-yl)piperidine;hydrochloride
• CAS: 65620-12-4
• 化学式: C₁₉H₂₇NO₂*ClH
• 分子量: 337.89
• InChiKey: XOYNGDYJHDBANS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.11
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  21.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-phenyl-4-(1-piperidinyl)cyclohexanone, ethylene ketal hydrochloride 在 盐酸 、 水 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 4',9'-dihydro-4-phenyl-4-(piperidin-1-yl)-3'H-spiro[cyclohexane-1,1'-pyrano[3,4-b]indole] methanesulfonate
  参考文献：
  名称：

  Discovery of a Potent Analgesic NOP and Opioid Receptor Agonist: Cebranopadol

  摘要：

  In a previous communication, our efforts leading from 1 to the identification of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amine 2a as analgesic NOP and opioid receptor agonist were disclosed and their favorable in vitro and in vivo pharmacological properties revealed. We herein report our efforts to further optimize lead 2a, toward trans-6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'(3'H)-pyrano[3,4-b]indol]-4-amine (cebranopadol, 3a), which is currently in clinical development for the treatment of severe chronic nociceptive and neuropathic pain.

  DOI：

  10.1021/ml500117c
• 作为产物：
  描述：

  1,4-环己二酮单乙二醇缩酮 在 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 4-phenyl-4-(1-piperidinyl)cyclohexanone, ethylene ketal hydrochloride
  参考文献：
  名称：

  Discovery of a Potent Analgesic NOP and Opioid Receptor Agonist: Cebranopadol

  摘要：

  In a previous communication, our efforts leading from 1 to the identification of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amine 2a as analgesic NOP and opioid receptor agonist were disclosed and their favorable in vitro and in vivo pharmacological properties revealed. We herein report our efforts to further optimize lead 2a, toward trans-6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'(3'H)-pyrano[3,4-b]indol]-4-amine (cebranopadol, 3a), which is currently in clinical development for the treatment of severe chronic nociceptive and neuropathic pain.

  DOI：

  10.1021/ml500117c

文献信息

• 4-Amino-4-phenylcyclohexanone ketal compositions and process of use
  申请人：The Upjohn Company

  公开号：US04065573A1

  公开（公告）日：1977-12-27

  A class of new 4-amino-4-arylcyclohexanones, their ketals, and acid addition salts have been synthesized and found to be useful for relieving pain in animals. Their analgesic activity appears to be of high order, and in addition some exhibit narcotic antagonist activity that is useful in modifying the cardiovascular, respiratory, and behavioral depression caused by other analgesics. Several show mixed analgesic and narcotic antagonist activity. Preferred compounds of the class are 4-(m-hydroxyphenyl)-4-dimethylaminocyclohexanone ethylene ketal, and 4-(m-hydroxyphenyl)-4-(n-butylmethylamino)cyclohexanone ethylene ketal as free bases and as their hydrochloride salts. Processes for synthesis and intermediates are described. Unit dosage forms and therapeutic treatments are disclosed.

  一类新的4-氨基-4-芳基环己酮，它们的缩醛和酸盐已经合成，并发现对于缓解动物的疼痛很有用。它们的镇痛活性似乎是很高的，并且一些还表现出对镇痛引起的心血管、呼吸和行为抑制有用的麻醉拮抗活性。其中几种显示出混合的镇痛和麻醉拮抗活性。该类化合物的首选化合物是4-(间羟基苯基)-4-二甲氨基环己酮乙二醚缩醛，以及4-(间羟基苯基)-4-(正丁基甲基氨基)环己酮乙二醚缩醛，作为游离碱和其盐酸盐形式。描述了合成和中间体的过程。披露了单位剂量形式和治疗方法。