tert-butyl 2-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}phenyl)-7-azaspiro[3.5]nonane-7-carboxylate | 1225276-03-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl 2-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}phenyl)-7-azaspiro[3.5]nonane-7-carboxylate
• 英文别名: tert-butyl 2-[3-[5-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-7-azaspiro[3.5]nonane-7-carboxylate
• CAS: 1225276-03-8
• 化学式: C₂₅H₂₉F₃N₂O₃
• 分子量: 462.512
• InChiKey: UEOWLAZZNJYQPW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  51.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}phenyl)-7-azaspiro[3.5]nonane-7-carboxylate 在 盐酸 、 水 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙腈 为溶剂， 生成 N-pyridin-3-yl-2-[3-[5-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-7-azaspiro[3.5]nonane-7-carboxamide
  参考文献：
  名称：

  Discovery of novel spirocyclic inhibitors of fatty acid amide hydrolase (FAAH). Part 1: Identification of 7-azaspiro[3.5]nonane and 1-oxa-8-azaspiro[4.5]decane as lead scaffolds

  摘要：

  Herein we report the identification of two new fatty acid amide hydrolase (FAAH) inhibitor lead series with FAAH k(inact)/K(i) potency values greater than 1500 M (1) s (1). The two novel spirocyclic cores, 7-azaspiro[3.5]nonane and 1-oxa-8-azaspiro[4.5]decane, clearly distinguished themselves from the other spirocyclic cores on the basis of their superior potency for FAAH. Lead compounds from these two series have suitable FAAH potency and selectivity for additional medicinal chemistry optimization. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.055
• 作为产物：
  描述：

  tert-butyl 2-(3-hydroxyphenyl)-7-azaspiro[3.5]nonane-7-carboxylate 、 2-氯-5-三氟甲基吡啶 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以85%的产率得到tert-butyl 2-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}phenyl)-7-azaspiro[3.5]nonane-7-carboxylate
  参考文献：
  名称：

  7-AZASPIRO[3.5]NONANE-7-CARBOXAMIDE COMPOUNDS

  摘要：

  本文提供了7-azaspiro[3.5]nonane-7-carboxamide化合物及其药用可接受盐，用于治疗与脂肪酸酰胺水解酶（FAAH）活性相关的疾病或症状，包括急性疼痛、慢性疼痛、神经病性疼痛、伤害性疼痛、炎症性疼痛、癌症及癌症疼痛、纤维肌痛、类风湿性关节炎、炎症性肠病、狼疮、糖尿病、过敏性哮喘、血管炎症、尿失禁、膀胱过度活跃、呕吐、认知障碍、焦虑、抑郁、睡眠障碍、进食障碍、运动障碍、青光眼、牛皮癣、多发性硬化、脑血管疾病、脑损伤、胃肠道疾病、高血压或心血管疾病。

  公开号：

  US20100113465A1

文献信息

• 7-AZASPIRO[3.5]NONANE-7-CARBOXAMIDE COMPOUNDS
  申请人：Long Scott A.

  公开号：US20100113465A1

  公开（公告）日：2010-05-06

  Provided herein are 7-azaspiro[3.5]nonane-7-carboxamide compounds and the pharmaceutically acceptable salts of such compounds useful in treating diseases or conditions associated with fatty acid amide hydrolase (FAAH) activity, conditions including including acute pain, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain, cancer and cancer pain, fibromyalgia, rheumatoid arthritis, inflammatory bowel disease, lupus, diabetes, allergic asthma, vascular inflammation, urinary incontinence, overactive bladder, emesis, cognitive disorders, anxiety, depression, sleeping disorders, eating disorders, movement disorders, glaucoma, psoriasis, multiple sclerosis, cerebrovascular disorders, brain injury, gastrointestinal disorders, hypertension, or cardiovascular disease.

  本文提供了7-azaspiro[3.5]nonane-7-carboxamide化合物及其药用可接受盐，用于治疗与脂肪酸酰胺水解酶（FAAH）活性相关的疾病或症状，包括急性疼痛、慢性疼痛、神经病性疼痛、伤害性疼痛、炎症性疼痛、癌症及癌症疼痛、纤维肌痛、类风湿性关节炎、炎症性肠病、狼疮、糖尿病、过敏性哮喘、血管炎症、尿失禁、膀胱过度活跃、呕吐、认知障碍、焦虑、抑郁、睡眠障碍、进食障碍、运动障碍、青光眼、牛皮癣、多发性硬化、脑血管疾病、脑损伤、胃肠道疾病、高血压或心血管疾病。
• [EN] 7-AZASPIRO [3.5] NONANE-7-CARBOXAMIDE COMPOUNDS AS MODULATORS OF FATTY ACID AMIDE HYDROLASE<br/>[FR] COMPOSÉS 7-AZASPIRO[3.5]NONANE-7-CARBOXAMIDE COMME MODULATEURS DE L'HYDROLASE D'AMIDES D'ACIDES GRAS
  申请人：PFIZER

  公开号：WO2010049841A1

  公开（公告）日：2010-05-06

  Provided herein are 7-azaspiro[3.5]nonane-7-carboxamide compounds and the pharmaceutically acceptable salts of such compounds useful in treating diseases or conditions associated with fatty acid amide hydrolase (FAAH) activity, conditions including including acute pain, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain, cancer and cancer pain, fibromyalgia, rheumatoid arthritis, inflammatory bowel disease, lupus, diabetes, allergic asthma, vascular inflammation, urinary incontinence, overactive bladder, emesis, cognitive disorders, anxiety, depression, sleeping disorders, eating disorders, movement disorders, glaucoma, psoriasis, multiple sclerosis, cerebrovascular disorders, brain injury, gastrointestinal disorders, hypertension, or cardiovascular disease.

  本文提供了7-azaspiro[3.5]nonane-7-carboxamide化合物及其药学上可接受的盐，用于治疗与脂肪酸酰胺水解酶（FAAH）活性相关的疾病或症状，包括急性疼痛、慢性疼痛、神经病理性疼痛、伤害性疼痛、炎症性疼痛、癌症和癌痛、纤维肌痛、类风湿性关节炎、炎症性肠病、狼疮、糖尿病、过敏性哮喘、血管炎症、尿失禁、膀胱过度活动、呕吐、认知障碍、焦虑、抑郁、睡眠障碍、进食障碍、运动障碍、青光眼、银屑病、多发性硬化症、脑血管疾病、脑损伤、胃肠道疾病、高血压或心血管疾病。
• Discovery of novel spirocyclic inhibitors of fatty acid amide hydrolase (FAAH). Part 2. Discovery of 7-azaspiro[3.5]nonane urea PF-04862853, an orally efficacious inhibitor of fatty acid amide hydrolase (FAAH) for pain
  作者：Marvin J. Meyers、Scott A. Long、Matthew J. Pelc、Jane L. Wang、Scott J. Bowen、Barbara A. Schweitzer、Mark V. Wilcox、Joseph McDonald、Sarah E. Smith、Susan Foltin、Jeanne Rumsey、Young-Sun Yang、Mark C. Walker、Satwik Kamtekar、David Beidler、Atli Thorarensen

  DOI：10.1016/j.bmcl.2011.08.048

  日期：2011.11

  Fatty acid amide hydrolase (FAAH) is an integral membrane serine hydrolase responsible for the degradation of fatty acid amide signaling molecules such as endocannabinoid anandamide (AEA), which has been shown to possess cannabinoid-like analgesic properties. Herein we report the optimization of spirocyclic 7-azaspiro[3.5]nonane and 1-oxa-8-azaspiro[4.5]decane urea covalent inhibitors of FAAH. Using an iterative design and optimization strategy, lead compounds were identified with a remarkable reduction in molecular weight and favorable CNS drug like properties. 3,4-Dimethylisoxazole and 1-methyltetrazole were identified as superior urea moieties for this inhibitor class. A dual purpose in vivo efficacy and pharmacokinetic screen was designed to be the key decision enabling experiment affording the ability to move quickly from compound synthesis to selection of preclinical candidates. On the basis of the remarkable potency, selectivity, pharmacokinetic properties and in vivo efficacy, PF-04862853 (15p) was advanced as a clinical candidate. (C) 2011 Elsevier Ltd. All rights reserved.
• 7-azaspiro [3.5]nonane-7-carboxamide compounds as modulators of fatty acid amide hydrolase
  申请人：Pfizer Inc.

  公开号：EP2358704A1

  公开（公告）日：2011-08-24
• Discovery of novel spirocyclic inhibitors of fatty acid amide hydrolase (FAAH). Part 1: Identification of 7-azaspiro[3.5]nonane and 1-oxa-8-azaspiro[4.5]decane as lead scaffolds
  作者：Marvin J. Meyers、Scott A. Long、Matthew J. Pelc、Jane L. Wang、Scott J. Bowen、Mark C. Walker、Barbara A. Schweitzer、Heather M. Madsen、Ruth E. Tenbrink、Joseph McDonald、Sarah E. Smith、Susan Foltin、David Beidler、Atli Thorarensen

  DOI：10.1016/j.bmcl.2011.08.055

  日期：2011.11

  Herein we report the identification of two new fatty acid amide hydrolase (FAAH) inhibitor lead series with FAAH k(inact)/K(i) potency values greater than 1500 M (1) s (1). The two novel spirocyclic cores, 7-azaspiro[3.5]nonane and 1-oxa-8-azaspiro[4.5]decane, clearly distinguished themselves from the other spirocyclic cores on the basis of their superior potency for FAAH. Lead compounds from these two series have suitable FAAH potency and selectivity for additional medicinal chemistry optimization. (C) 2011 Elsevier Ltd. All rights reserved.