N-{5-bromo-2-[(cyclopropylmethyl)amino]phenyl}-3,3-dimethylbutanamide | 886049-64-5

• 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: N-{5-bromo-2-[(cyclopropylmethyl)amino]phenyl}-3,3-dimethylbutanamide
• 英文别名: N-[5-bromo-2-(cyclopropylmethylamino)phenyl]-3,3-dimethylbutanamide
• CAS: 886049-64-5
• 化学式: C₁₆H₂₃BrN₂O
• 分子量: 339.275
• InChiKey: SWUICPXRXNVZRZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-{5-bromo-2-[(cyclopropylmethyl)amino]phenyl}-3,3-dimethylbutanamide 在 盐酸 、 sodium tungstate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 三甲基氯硅烷 、 双氧水 、 三乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 乙腈 为溶剂， 反应 1.0h， 生成 5-(azetidine-3-sulfonyl)-1-(cyclopropylmethyl)-2-(2,2-dimethylpropyl)-1H-benzoimidazole
  参考文献：
  名称：

  Identification of a highly potent and selective CB2 agonist, RQ-00202730, for the treatment of irritable bowel syndrome

  摘要：

  Herein we report the identification of a highly potent and selective CB2 agonist, RQ-00202730 (40), obtained by lead optimization of the benzimidazole scaffold. Compound 40 showed strong agonistic activity with an EC50 of 19 nM and excellent selectivity (>1300-fold) over the CB1 receptor. Compound 40 displayed a dose dependent analgesic effect on TNBS-induced visceral hypersensitivity in rats by oral administration (ED50 0.66 mg/kg at 2.5 h after oral administration). In addition, 40 did not show a significant effect on body temperature in rats after oral administration at 300 mg/kg. These findings suggest that highly selective CB2 agonists will be effective agents for IBS therapy. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.11.062
• 作为产物：
  描述：

  2,5-二溴硝基苯 在 铁粉 、 氯化铵 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 水 、 乙酸乙酯 为溶剂， 反应 23.0h， 生成 N-{5-bromo-2-[(cyclopropylmethyl)amino]phenyl}-3,3-dimethylbutanamide
  参考文献：
  名称：

  Optimisation of a novel series of selective CNS penetrant CB2 agonists

  摘要：

  A series of benzimidazole CB2 receptor agonists were prepared and their properties investigated. Optimisation of the three benzimidazole substituents led to the identification of compound 23, a potent CB2 full agonist (EC50 2.7 nM) with excellent selectivity over the CB1 receptor (> 3000-fold). Compound 23 demonstrated good CNS penetration in rat. Further optimisation led to the identification of compound 34 with improved selectivity over hERG and excellent CNS penetration in rat. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.063

文献信息

• [EN] N-SUBSTITUTED SATURATED HETEROCYCLIC SULFONE COMPOUNDS WITH CB2 RECEPTOR AGONISTIC ACTIVITY<br/>[FR] COMPOSÉS DE SULFONE HÉTÉROCYCLIQUES SATURÉS N-SUBSTITUÉS AYANT UNE ACTIVITÉ AGONISTE DU RÉCEPTEUR CB2
  申请人：RAQUALIA PHARMA INC

  公开号：WO2010084767A1

  公开（公告）日：2010-07-29

  This invention relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein X, R1, R2,R3, R4, R5, R6, R7, k, m, n, p, q, r and s are each as described herein, and compositions containing such compounds, and the use of such compounds in the treatment of a condition mediated by CB2 receptor activity.

  这项发明涉及式(I)的化合物或其药用盐，其中X、R1、R2、R3、R4、R5、R6、R7、k、m、n、p、q、r和s如本文所述，并含有这种化合物的组合物，以及利用这种化合物治疗由CB2受体活性介导的疾病的用途。
• Compounds Which Selectively Modulate The CB2 Receptor
  申请人：BARTOLOZZI Alessandra

  公开号：US20100076029A1

  公开（公告）日：2010-03-25

  Compounds of formula (I) are disclosed. Compounds according to the invention bind to and are agonists, antagonists or inverse agonists of the CB2 receptor, and are useful for treating inflammation. Those compounds which are agonists are additionally useful for treating pain.

  公式（I）的化合物已被披露。根据本发明的化合物与CB2受体结合，并且是CB2受体的激动剂、拮抗剂或反向激动剂，可用于治疗炎症。那些是激动剂的化合物还可用于治疗疼痛。
• Sulfonyl benzimidazole derivatives
  申请人：Kon-I Kana

  公开号：US20060094750A1

  公开（公告）日：2006-05-04

  This invention relates to compounds of the formula (I): or a pharmaceutically acceptable salt thereof, wherein A, B, R 1 , R 2 and R 3 are each as described herein, and compositions containing such compounds, and the use of such compounds in the treatment of a condition mediated by CB2 receptor activity such as, but not limited to, inflammatory pain, nociceptive pain, neuropathic pain, fibromyalgia, chronic low back pain, visceral pain, acute cerebral ischemia, pain, chronic pain, acute pain, post herpetic neuralgia, neuropathies, neuralgia, diabetic neuropathy, HIV-related neuropathy, nerve injury, rheumatoid arthritic pain, osteoarthritic pain, back pain, cancer pain, dental pain, fibromyalgia, neuritis, sciatica, inflammation, neurodegenerative disease, cough, broncho constriction, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colitis, cerebrovascular ischemia, emesis such as cancer chemotherapy-induced emesis, rheumatoid arthritis, asthma, Crohn's disease, ulcerative colitis, asthma, dermatitis, seasonal allergic rhinitis, GERD, constipation, diarrhea, functional gastrointestinal disorders, irritable bowel syndrome, cutaneous T cell lymphoma, multiple sclerosis, osteoarthritis, psoriasis, systemic lupus erythematosus, diabetes, glaucoma, osteoporosis, glomerulonephritis, renal ischemia, nephritis, hepatitis, cerebral stroke, vasculitis, myocardial infarction, cerebral ischemia, reversible airway obstruction, adult respiratory disease syndrome, COPD, cryptogenic fibrosing alveolitis and bronchitis.

  本发明涉及以下式（I）的化合物或其药学上可接受的盐，其中A、B、R1、R2和R3如本文所述，并含有此类化合物的组合物，以及利用此类化合物治疗由CB2受体活性介导的病况，例如但不限于炎症性疼痛、伤害性疼痛、神经病性疼痛、纤维肌痛、慢性腰痛、内脏疼痛、急性脑缺血、疼痛、慢性疼痛、急性疼痛、带状疱疹后神经痛、神经病、神经痛、糖尿病神经病、艾滋病相关神经病、神经损伤、类风湿关节痛、骨关节痛、背痛、癌痛、牙痛、纤维肌痛、神经炎、坐骨神经痛、炎症、神经退行性疾病、咳嗽、支气管痉挛、肠易激综合征（IBS）、炎症性肠病（IBD）、结肠炎、脑血管缺血、呕吐，如癌症化疗引起的呕吐、类风湿性关节炎、哮喘、克罗恩病、溃疡性结肠炎、皮炎、季节性过敏性鼻炎、胃食管反流病（GERD）、便秘、腹泻、功能性胃肠疾病、肠易激综合征、皮肤T细胞淋巴瘤、多发性硬化症、骨关节炎、牛皮癣、系统性红斑狼疮、糖尿病、青光眼、骨质疏松症、肾小球肾炎、肾缺血、肾炎、肝炎、脑卒中、血管炎、心肌梗死、脑缺血、可逆气道梗阻、成人呼吸系统疾病综合征、慢性阻塞性肺疾病（COPD）、隐源性纤维化性肺炎和支气管炎。
• SULFONYL BENZIMIDAZOLE DERIVATIVES
  申请人：Kato Tomoki

  公开号：US20090137584A1

  公开（公告）日：2009-05-28

  This invention relates to compounds of the formula (I): or a pharmaceutically acceptable salt thereof, wherein A, R 1 , R 2 , R 3 , R 4 , R 5 , m and n are each as described herein, and compositions containing such compounds, and the use of such compounds in the treatment of a condition mediated by CB2 receptor activity such as, but not limited to, inflammatory pain, nociceptive pain, neuropathic pain, fibromyalgia, chronic low back pain, visceral pain, acute cerebral ischemia, pain, chronic pain, acute pain, post herpetic neuralgia, neuropathies, neuralgia, diabetic neuropathy, HIV-related neuropathy, nerve injury, rheumatoid arthritic pain, osteoarthritic pain, back pain, cancer pain, dental pain, fibromyalgia, neuritis, sciatica, inflammation, neurodegenerative disease, cough, broncho constriction, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colitis, cerebrovascular ischemia, emesis such as cancer chemotherapy-induced emesis, rheumatoid arthritis, asthma, Crohn's disease, ulcerative colitis, asthma, dermatitis, seasonal allergic rhinitis, GERD, constipation, diarrhea, functional gastrointestinal disorders, irritable bowel syndrome, cutaneous T cell lymphoma, multiple sclerosis, osteoarthritis, psoriasis, systemic lupus erythematosus, diabetes, glaucoma, osteoporosis, glomerulonephritis, renal ischemia, nephritis, hepatitis, cerebral stroke, vasculitis, myocardial infarction, cerebral ischemia, reversible airway obstruction, adult respiratory disease syndrome, COPD, cryptogenic fibrosing alveolitis and bronchitis.

  本发明涉及化合物公式(I)或其药学上可接受的盐，其中A、R1、R2、R3、R4、R5、m和n分别如本文所述，以及含有这种化合物的组合物，以及这种化合物在治疗CB2受体活性介导的疾病中的应用，例如但不限于炎症性疼痛、伤害性疼痛、神经病理性疼痛、纤维肌痛、慢性腰痛、内脏疼痛、急性脑缺血、疼痛、慢性疼痛、急性疼痛、带状疱疹后神经痛、神经病、神经痛、糖尿病神经病、艾滋病相关神经病、神经损伤、类风湿性关节炎疼痛、骨关节炎疼痛、背痛、癌痛、牙痛、纤维肌痛、神经炎、坐骨神经痛、炎症、神经退行性疾病、咳嗽、支气管收缩、肠易激综合症(IBS)、炎症性肠病(IBD)、结肠炎、脑血管缺血、呕吐，例如癌症化疗引起的呕吐、类风湿性关节炎、哮喘、克罗恩病、溃疡性结肠炎、哮喘、皮炎、季节性过敏性鼻炎、GERD、便秘、腹泻、功能性胃肠疾病、肌肤T细胞淋巴瘤、多发性硬化症、骨关节炎、银屑病、系统性红斑狼疮、糖尿病、青光眼、骨质疏松症、肾小球肾炎、肾脏缺血、肾炎、肝炎、脑卒中、血管炎、心肌梗死、脑缺血、可逆性气道阻塞、成人呼吸系统疾病综合症、COPD、隐源性纤维化性肺泡炎和支气管炎等。
• WO2007/102059
  申请人：——

  公开号：——

  公开（公告）日：——