(S)-N-benzyl-1-fluoro-3-methylbutan-2-amine

• 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: (S)-N-benzyl-1-fluoro-3-methylbutan-2-amine
• 英文别名: (2S)-N-benzyl-1-fluoro-3-methylbutan-2-amine
• 化学式: C₁₂H₁₈FN
• 分子量: 195.28
• InChiKey: ASZFOLHAOKEXMZ-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-N-benzyl-1-fluoro-3-methylbutan-2-amine 在 5%-palladium/activated carbon 、 氢气 、 盐酸 作用下， 以 甲醇 为溶剂， 23.0 ℃ 、861.86 kPa 条件下， 反应 15.0h， 以59%的产率得到(S)-1-fluoro-3-methylbutan-2-amine hydrochloride
  参考文献：
  名称：

  Discovery of APD371: Identification of a Highly Potent and Selective CB₂ Agonist for the Treatment of Chronic Pain

  摘要：

  The discovery of a novel, selective and fully efficacious CB2 agonist with satisfactory pharmacokinetic and pharmaceutical properties is described. Compound 6 was efficacious in a rat model of osteoarthritis pain following oral administration and, in contrast to morphine, maintained its analgesic effect throughout a 5-day subchronic treatment paradigm. These data were consistent with our hypothesis that full agonist efficacy is required for efficient internalization and recycling of the CB2 receptor to avoid tachyphylaxis. Based on its overall favorable preclinical profile, 6 (APD371) was selected for further development for the treatment of pain.

  DOI：

  10.1021/acsmedchemlett.7b00396
• 作为产物：
  描述：

  (S)-3-methyl-2-{[1-phenylmethylidene]amino}butan-1-ol 在 ruthenium trichloride 、 sodium periodate 、 氯化亚砜 、 sodium cyanoborohydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 0.83h， 生成 (S)-N-benzyl-1-fluoro-3-methylbutan-2-amine
  参考文献：
  名称：

  Discovery of APD371: Identification of a Highly Potent and Selective CB₂ Agonist for the Treatment of Chronic Pain

  摘要：

  The discovery of a novel, selective and fully efficacious CB2 agonist with satisfactory pharmacokinetic and pharmaceutical properties is described. Compound 6 was efficacious in a rat model of osteoarthritis pain following oral administration and, in contrast to morphine, maintained its analgesic effect throughout a 5-day subchronic treatment paradigm. These data were consistent with our hypothesis that full agonist efficacy is required for efficient internalization and recycling of the CB2 receptor to avoid tachyphylaxis. Based on its overall favorable preclinical profile, 6 (APD371) was selected for further development for the treatment of pain.

  DOI：

  10.1021/acsmedchemlett.7b00396

文献信息

• [EN] CANNABINOID RECEPTOR MODULATORS<br/>[FR] MODULATEURS DES RÉCEPTEURS DE CANNABINOÏDES
  申请人：ARENA PHARM INC

  公开号：WO2011025541A1

  公开（公告）日：2011-03-03

  The present invention relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor. The present invention further relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activities of both the CB1 receptor and the CB2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pain, for example bone and joint pain, muscle pain, dental pain, migraine and other headache pain, inflammatory pain, neuropathic pain, pain that occurs as an adverse effect of therapeutics and pain associated with osteoarthritis; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions; CNS inflammation; atherosclerosis; undesired immune cell activity and inflammation; age-related macular degeneration; cough; leukemia; lymphoma; CNS tumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis, and Parkinson's disease.

  本发明涉及某些化合物Ia的配方和调节大麻素CB2受体活性的药物组合物。本发明还涉及某些化合物Ia的配方和药物组合物，其调节CB1受体和CB2受体的活性。本发明的化合物和药物组合物用于治疗以下疾病的方法：疼痛，例如骨骼和关节疼痛，肌肉疼痛，牙痛，偏头痛和其他头痛，炎症性疼痛，神经痛，作为治疗的不良反应而发生的疼痛以及与骨关节炎相关的疼痛；痛觉过敏；触觉过敏；炎症性痛觉过敏；神经痛觉过敏；急性疼痛感；骨质疏松症；多发性硬化症相关的痉挛；自身免疫性疾病；过敏反应；中枢神经系统炎症；动脉粥样硬化；不良的免疫细胞活性和炎症；年龄相关的黄斑变性；咳嗽；白血病；淋巴瘤；中枢神经系统肿瘤；前列腺癌；阿尔茨海默病；中风引起的损伤；痴呆症；肌萎缩侧索硬化和帕金森病。
• CANNABINOID RECEPTOR MODULATORS
  申请人：Jones Robert M.

  公开号：US20120214766A1

  公开（公告）日：2012-08-23

  The present invention relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor. The present invention further relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activities of both the CB1 receptor and the CB2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pain, for example bone and joint pain, muscle pain, dental pain, migraine and other headache pain, inflammatory pain, neuropathic pain, pain that occurs as an adverse effect of therapeutics and pain associated with osteoarthritis; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions; CNS inflammation; atherosclerosis; undesired immune cell activity and inflammation; age-related macular degeneration; cough; leukemia; lymphoma; CNS tumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis, and Parkinson's disease.

  本发明涉及公式Ia的某些化合物及其制药组合物，其调节大麻素CB2受体的活性。本发明还涉及公式Ia的某些化合物及其制药组合物，其调节CB1受体和CB2受体的活性。本发明的化合物和制药组合物适用于治疗以下疾病的方法：疼痛，例如骨骼和关节疼痛，肌肉疼痛，牙痛，偏头痛和其他头痛，炎性疼痛，神经痛，由治疗副作用引起的疼痛和与骨关节炎相关的疼痛；过敏症；炎性过敏症；神经病性过敏症；急性疼痛感受；骨质疏松症；多发性硬化症相关痉挛；自身免疫疾病；过敏反应；中枢神经系统炎症；动脉粥样硬化；不良的免疫细胞活动和炎症；年龄相关的黄斑变性；咳嗽；白血病；淋巴瘤；中枢神经系统肿瘤；前列腺癌；阿尔茨海默病；中风引起的损伤；痴呆症；肌萎缩性侧索硬化症和帕金森病。
• Cannabinoid receptor modulators
  申请人：Jones Robert M.

  公开号：US08778950B2

  公开（公告）日：2014-07-15

  The present invention relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor. The present invention further relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activities of both the CB1 receptor and the CB2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pain, for example bone and joint pain, muscle pain, dental pain, migraine and other headache pain, inflammatory pain, neuropathic pain, pain that occurs as an adverse effect of therapeutics and pain associated with osteoarthritis; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions; CNS inflammation; atherosclerosis; undesired immune cell activity and inflammation; age-related macular degeneration; cough; leukemia; lymphoma; CNS tumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis, and Parkinson's disease.

  本发明涉及化合物Ia的某些化合物及其制药组合物，该化合物调节大麻素CB2受体的活性。本发明还涉及化合物Ia的某些化合物及其制药组合物，该化合物调节CB1受体和CB2受体的活性。本发明的化合物及其制药组合物适用于治疗以下疾病的方法：疼痛，例如骨骼和关节疼痛，肌肉疼痛，牙痛，偏头痛和其他头痛，炎症性疼痛，神经痛，作为治疗副作用发生的疼痛和与骨关节炎有关的疼痛；高痛觉性；触痛；炎症性高痛觉性；神经病性高痛觉性；急性伤害感受；骨质疏松症；多发性硬化相关痉挛；自身免疫性疾病；过敏反应；中枢神经系统炎症；动脉硬化；不良的免疫细胞活性和炎症；年龄相关的黄斑变性；咳嗽；白血病；淋巴瘤；中枢神经系统肿瘤；前列腺癌；阿尔茨海默病；中风引起的损伤；痴呆症；肌萎缩性侧索硬化症和帕金森病。
• US8778950B2
  申请人：——

  公开号：US8778950B2

  公开（公告）日：2014-07-15
• US9944606B2
  申请人：——

  公开号：US9944606B2

  公开（公告）日：2018-04-17