4-amino-1-(cyclooctylmethyl)piperidine | 342807-55-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-amino-1-(cyclooctylmethyl)piperidine
• 英文别名: 1-(Cyclooctylmethyl)piperidin-4-amine
• CAS: 342807-55-0
• 化学式: C₁₄H₂₈N₂
• 分子量: 224.39
• InChiKey: FWCYCEJJKSJDCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  二苯基羟基乙酸 、 4-amino-1-(cyclooctylmethyl)piperidine 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 13.0h， 以45%的产率得到N-(1-Cyclooctylmethyl-piperidin-4-yl)-2-hydroxy-2,2-diphenyl-acetamide
  参考文献：
  名称：

  Design, Synthesis, and Discovery of a Novel CCR1 Antagonist

  摘要：

  The CC chemokines may play an important role in the pathogenesis of chronic inflammatory diseases including rheumatoid arthritis, and their effects are thought to be mediated through CCR1 receptors. Several nonpeptide CCR1 receptor antagonists that showed high affinity for human CCR1 receptors have been identified; however, their effectiveness in animal models of inflammatory diseases has been scarcely demonstrated, probably due to species selectivity of the antagonists. To elucidate the pathophysiological role of CCR1 receptors in murine models of disease, we looked for a potent antagonist for both murine and human CCR1 receptors. Screening of our chemical collection for inhibition of I-125-MIP-1 alpha. binding to human CCR1 receptors transfected in CHO cells led to the identification of xanthene-9-carboxamide la as the lead compound. Derivatization of 1a by quaternarizing the piperidine nitrogen with various alkyl groups and by installing substituents into the xanthene moiety dramatically improved the inhibitory activity against both human and murine CCR1 receptors. As a result, 2q-1 showing IC50 values of 0.9 and 5.8 nM for human and murine CCR1 receptors, respectively, was discovered. This compound is the first murine CCR1 receptor antagonist and may be a useful tool for clarifying the role of CCR1 receptors in murine models of disease.

  DOI：

  10.1021/jm0004244
• 作为产物：
  描述：

  4-叔丁氧羰基氨基哌啶 在 盐酸 、 三乙酰氧基硼氢化钠 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 40.0h， 生成 4-amino-1-(cyclooctylmethyl)piperidine
  参考文献：
  名称：

  Design, Synthesis, and Discovery of a Novel CCR1 Antagonist

  摘要：

  The CC chemokines may play an important role in the pathogenesis of chronic inflammatory diseases including rheumatoid arthritis, and their effects are thought to be mediated through CCR1 receptors. Several nonpeptide CCR1 receptor antagonists that showed high affinity for human CCR1 receptors have been identified; however, their effectiveness in animal models of inflammatory diseases has been scarcely demonstrated, probably due to species selectivity of the antagonists. To elucidate the pathophysiological role of CCR1 receptors in murine models of disease, we looked for a potent antagonist for both murine and human CCR1 receptors. Screening of our chemical collection for inhibition of I-125-MIP-1 alpha. binding to human CCR1 receptors transfected in CHO cells led to the identification of xanthene-9-carboxamide la as the lead compound. Derivatization of 1a by quaternarizing the piperidine nitrogen with various alkyl groups and by installing substituents into the xanthene moiety dramatically improved the inhibitory activity against both human and murine CCR1 receptors. As a result, 2q-1 showing IC50 values of 0.9 and 5.8 nM for human and murine CCR1 receptors, respectively, was discovered. This compound is the first murine CCR1 receptor antagonist and may be a useful tool for clarifying the role of CCR1 receptors in murine models of disease.

  DOI：

  10.1021/jm0004244

文献信息

• [EN] SUBSTITUTED BENZIMIDAZOLES AS NOCICEPTIN RECEPTOR MODULATORS<br/>[FR] BENZIMIDAZOLES SUBSTITUÉS EN TANT QUE MODULATEURS D'UN RÉCEPTEUR DE NOCICEPTINE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2014153529A1

  公开（公告）日：2014-09-25

  The invention provides modulators of the nociceptin receptor (NOP), including both agonists and antagonists. A compound of the invention can be a selective modulator of NOP with respect to the μ- and κ- opioid receptors (MOP and KOP), thus providing a therapeutic method for the treatment of conditions wherein selective NOP modulation is medically indicated and MOP or KOP modulation may be less desirable. A compound of the invention can be a NOP full agonist, partial agonist, inverse agonist, positive or negative allosteric modulator, or a functionally biased agonist. A compound of the invention can be used for the treatment of an anxiety state, post-traumatic stress disorder, addictive disorders (including overuse of alcohol, tobacco, and drugs of abuse such as cocaine, amphetamines, and opitates), misregulated food intake and/or energy expenditure, cough, sleep disorders, migraine, pain, depression, or neurodegenerative disorders such as Parkinsons disease or Alzheimers disease.

  该发明提供了辅料受体（NOP）的调节剂，包括激动剂和拮抗剂。该发明的化合物可以是NOP的选择性调节剂，相对于μ-和κ-阿片受体（MOP和KOP），因此提供了一种治疗方法，用于治疗需要选择性NOP调节而MOP或KOP调节可能不太理想的疾病。该发明的化合物可以是NOP的全激动剂、部分激动剂、逆激动剂、正或负变构调节剂，或功能性偏向激动剂。该发明的化合物可用于治疗焦虑状态、创伤后应激障碍、成瘾性障碍（包括滥用酒精、烟草和可卡因、安非他明和阿片类等药物）、食物摄入和/或能量消耗失调、咳嗽、睡眠障碍、偏头痛、疼痛、抑郁症，或帕金森病或阿尔茨海默病等神经退行性疾病的治疗。
• SUBSTITUTED BENZIMIDAZOLES AS NOCICEPTIN RECEPTOR MODULATORS
  申请人：THE SCRIPPS RESEARCH INSTITUTE

  公开号：US20160052913A1

  公开（公告）日：2016-02-25

  The invention provides modulators of the nociceptin receptor (NOP), including both agonists and antagonists. A compound of the invention can be a selective modulator of NOP with respect to the μ- and κ-opioid receptors (MOP and KOP), thus providing a therapeutic method for the treatment of conditions wherein selective NOP modulation is medically indicated and MOP or KOP modulation may be less desirable. A compound of the invention can be a NOP full agonist, partial agonist, inverse agonist, positive or negative allosteric modulator, or a functionally biased agonist. A compound of the invention can be used for the treatment of an anxiety state, post-traumatic stress disorder, addictive disorders (including overuse of alcohol, tobacco, and drugs of abuse such as cocaine, amphetamines, and opitates), misregulated food intake and/or energy expenditure, cough, sleep disorders, grain, pain, depression, or neurodegenerative disorders such as Parkinsons disease or Alzheimers disease.

  本发明提供了诺西普针受体(NOP)的调节剂，包括激动剂和拮抗剂。本发明的化合物可以是NOP的选择性调节剂，相对于μ-和κ-阿片受体(MOP和KOP)，从而为治疗选择性NOP调节在医学上指示和MOP或KOP调节可能不太理想的情况提供治疗方法。本发明的化合物可以是NOP的全激动剂、部分激动剂、反向激动剂、正或负的变构调节剂，或功能偏向激动剂。本发明的化合物可用于治疗焦虑状态、创伤后应激障碍、成瘾性障碍(包括滥用酒精、烟草和滥用药物，如可卡因、安非他命和阿片类药物)、不当的食物摄入和/或能量消耗、咳嗽、睡眠障碍、谷物、疼痛、抑郁症或神经退行性疾病，如帕金森病或阿尔茨海默病的治疗。
• 2-OXOIMIDAZOLE DERIVATIVES
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP0990653A1

  公开（公告）日：2000-04-05

  The present invention relates to a compound represented by Formula [I] [wherein represents an aromatic carbo- or heterocyclic ring which may have a substituent; Cy represents a mono-, bi- or tricyclic aliphatic carbocyclic group having 3 to 20 carbon atoms, which may have a substituent; represents a mono- or bicyclic aliphatic nitrogen-containing heterocyclic group having 3 to 14 carbon atoms, which may have a substituent; R1 represents a hydrogen atom, a lower alkenyl group, a lower alkynyl group, a cyclo(lower alkyl) group, an amino group, a lower alkylamino group, a di(lower alkyl)amino group, a hydroxyl group, a lower alkoxy group, a carboxyl group, a lower alkoxycarbonyl group, a carbamoyl group, a lower alkylcarbamoyl group or a di(lower alkyl)carbamoyl group, or a lower alkyl group which may have a substituent; and R 2 represents a hydrogen atom or a lower alkyl group], a salt or ester thereof, a production process for the same, and an analgesic, a reliever against tolerance to a narcotic analgesic represented by morphine, a reliever against dependence on a narcotic analgesic represented by morphine, an analgesic enhancer, an antiobestic, a drug for ameliorating brain function, a remedy for schizophrenia, a remedy for Parkinsonism, a remedy for chorea, an antidepressant, a remedy for diabetes insipidus, a remedy for polyuria, or a remedy for hypotension, comprising an effective ingredient of the same.

  本发明涉及一种由式[I]表示的化合物 其中 代表芳香族碳环或杂环，可以有取代基； Cy 代表具有 3 至 20 个碳原子的单环、双环或三环脂族碳环基团，可以有取代基； 代表具有 3 至 14 个碳原子的单环或双环脂族含氮杂环基团，该基团可具有取代基；R1 代表氢原子、低级烯基、低级炔基、环(低级烷基)基团、氨基、低级烷基氨基、二(低级烷基)氨基、羟基、低级烷氧基、羧基、低级烷氧羰基、氨基甲酰基、低级烷基氨基甲酰基或二(低级烷基)氨基甲酰基，或可带有取代基的低级烷基；以及 R 2 代表氢原子或低级烷基]，其盐或酯，其生产工艺，以及一种镇痛剂、一种防止对以吗啡为代表的麻醉性镇痛剂产生耐受性的缓解剂、一种防止对以吗啡为代表的麻醉性镇痛剂产生依赖性的缓解剂、一种镇痛增强剂、一种抗抑郁剂、一种改善脑功能的药物、一种治疗精神分裂症的药物、一种治疗帕金森病的药物、一种治疗舞蹈症的药物、一种抗抑郁剂、一种治疗糖尿病的药物、一种治疗多尿症的药物或一种治疗低血压的药物，其中包括一种有效成分。
• US6258825B1
  申请人：——

  公开号：US6258825B1

  公开（公告）日：2001-07-10
• US9656994B2
  申请人：——

  公开号：US9656994B2

  公开（公告）日：2017-05-23