N-((S)-1-(((R)-1-((2-cyanophenyl)sulfonyl)-3-oxoazepan-4-yl)amino)-4-methyl-1-oxopentan-2-yl)benzo[b]thiophene-2-carboxamide | 281216-75-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-((S)-1-(((R)-1-((2-cyanophenyl)sulfonyl)-3-oxoazepan-4-yl)amino)-4-methyl-1-oxopentan-2-yl)benzo[b]thiophene-2-carboxamide
• 英文别名: N-[(2S)-1-[[(4R)-1-(2-cyanophenyl)sulfonyl-3-oxoazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzothiophene-2-carboxamide
• CAS: 281216-75-9
• 化学式: C₂₈H₃₀N₄O₅S₂
• 分子量: 566.702
• InChiKey: UVJMMTJRRQWAIQ-YADHBBJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  173
• 氢给体数：
  2
• 氢受体数：
  8

文献信息

• [EN] TRPV4 ANTAGONISTS<br/>[FR] ANTAGONISTES DE TRPV4
  申请人：GLAXOSMITHKLINE IP NO 2 LTD

  公开号：WO2018055527A1

  公开（公告）日：2018-03-29

  The present invention relates to pyrrolidine sulfonamide analogs (I), pharmaceutical compositions containing them and their use as TRPV4 antagonists.

  本发明涉及吡咯烷磺酰胺类似物(I)、含有它们的药物组合物及其作为TRPV4拮抗剂的应用。
• [EN] TRPV4 ANTAGONIST<br/>[FR] ANTAGONISTE DE TRPV4
  申请人：GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO 2) LTD

  公开号：WO2017199199A1

  公开（公告）日：2017-11-23

  The present invention relates to a novel compound useful as a TRPV4 antagonist, specifically the compound 1-(((5S,7R)-3-(5-cyclopropylpyrazin-2-yl)-7-hydroxy-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile, pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compound. The compound of the invention can be useful in the treatment of a disease state selected from: atherosclerosis, disorders related to vasogenic edema, postsurgical abdominal edema, ocular edema, cerebral edema, local and systemic edema, fluid retention, sepsis, hypertension, inflammation, bone related dysfunctions and congestive heart failure, pulmonary disorders, chronic obstructive pulmonary disorder, ventilator induced lung injury, high altitude induced pulmonary edema, acute respiratory distress syndrome, acute lung injury, pulmonary fibrosis, sinusitis/rhinitis, asthma, cough; including acute cough, sub-acute cough and chronic cough, pulmonary hypertension, overactive bladder, cystitis, pain, motor neuron disorders, genetic gain of function disorders, cardiovascular disease, renal dysfunction, stroke, glaucoma, retinopathy, endometriosis, pre-term labor, dermatitis, pruritus, pruritus in liver disease, diabetes, metabolic disorder, obesity, migraine, pancreatitis, tumor suppression, immunosuppression, osteoarthritis, crohn's disease, colitis, diarrhea, intestinal irregularity (hyperreactivity/hyporeactivity), fecal incontinence, irritable bowel syndrome (IBS), constipation, intestinal pain and cramping, celiac disease, lactose intolerance, and flatulence.

  本发明涉及一种新型化合物，可用作TRPV4拮抗剂，具体为化合物1-(((5S,7R)-3-(5-环丙基吡嗪-2-基)-7-羟基-2-氧代-1-氧杂螺[4.5]癸烷-7-基)甲基)-1H-苯并[d]咪唑-6-碳腈，其药学上可接受的盐以及含有该化合物的药物组合物。本发明的化合物可用于治疗以下疾病状态：动脉粥样硬化，与血管源性水肿有关的疾病，术后腹部水肿，眼部水肿，脑水肿，局部和全身水肿，液体潴留，败血症，高血压，炎症，与骨相关的功能障碍和充血性心力衰竭，肺部疾病，慢性阻塞性肺疾病，呼吸机诱导的肺损伤，高海拔诱发的肺水肿，急性呼吸窘迫综合征，急性肺损伤，肺纤维化，鼻窦炎/鼻炎，哮喘，咳嗽；包括急性咳嗽、亚急性咳嗽和慢性咳嗽，肺动脉高压，膀胱过度活跃，膀胱炎，疼痛，运动神经元疾病，遗传性增强功能障碍，心血管疾病，肾功能障碍，中风，青光眼，视网膜病变，子宫内膜异位症，早产，皮炎，瘙痒，肝病瘙痒，糖尿病，代谢紊乱，肥胖，偏头痛，胰腺炎，肿瘤抑制，免疫抑制，骨关节炎，克罗恩病，结肠炎，腹泻，肠道不规则（过度反应/低反应），大便失禁，肠易激综合征（IBS），便秘，肠道疼痛和痉挛，乳糜泻，乳糖不耐受和胀气。
• Method for Activating Trpv4 Channel Receptors by Agonists
  申请人：Kumar Sanjay

  公开号：US20070259856A1

  公开（公告）日：2007-11-08

  This invention relates to methods for activating a TRPV4 channel receptor, thereby reducing the production and/or release of matrix degrading enzymes by a cell expressing a TRPV4 channel receptor, thereby reducing the breakdown of an extra-cellular matrix. Also contemplated within the scope of the invention are methods of attenuating the inhibition of matrix production.

  本发明涉及激活TRPV4通道受体的方法，从而减少表达TRPV4通道受体的细胞产生和/或释放基质降解酶，从而减少细胞外基质的分解。本发明还考虑了减轻基质生产抑制的方法。
• TRPV4 antagonists
  申请人：GlaxoSmithKline Intellectual Property (No. 2) Limited

  公开号：US10588891B2

  公开（公告）日：2020-03-17

  The present invention relates to pyrrolidine sulfonamide analogs, pharmaceutical compositions containing them and their use as TRPV4 antagonists.

  本发明涉及吡咯烷磺酰胺类似物、含有它们的药物组合物及其作为 TRPV4 拮抗剂的用途。
• TRPV4 antagonist
  申请人：GlaxoSmithKline Intellectual Property (No.2) Limited

  公开号：US10968209B2

  公开（公告）日：2021-04-06

  The present invention relates to a novel compound useful as a TRPV4 antagonist, specifically the compound 1-(((5S,7R)-3-(5-cyclopropylpyrazin-2-yl)-7-hydroxy-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile, pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compound. The compound of the invention can be useful in the treatment of a disease state selected from: atherosclerosis, disorders related to vasogenic edema, postsurgical abdominal edema, ocular edema, cerebral edema, local and systemic edema, fluid retention, sepsis, hypertension, inflammation, bone related dysfunctions and congestive heart failure, pulmonary disorders, chronic obstructive pulmonary disorder, ventilator induced lung injury, high altitude induced pulmonary edema, acute respiratory distress syndrome, acute lung injury, pulmonary fibrosis, sinusitis/rhinitis, asthma, cough; including acute cough, sub-acute cough and chronic cough, pulmonary hypertension, overactive bladder, cystitis, pain, motor neuron disorders, genetic gain of function disorders, cardiovascular disease, renal dysfunction, stroke, glaucoma, retinopathy, endometriosis, pre-term labor, dermatitis, pruritus, pruritus in liver disease, diabetes, metabolic disorder, obesity, migraine, pancreatitis, tumor suppression, immunosuppression, osteoarthritis, crohn's disease, colitis, diarrhea, intestinal irregularity (hyperreactivity/hyporeactivity), fecal incontinence, irritable bowel syndrome (IBS), constipation, intestinal pain and cramping, celiac disease, lactose intolerance, and flatulence.

  本发明涉及一种可用作TRPV4拮抗剂的新型化合物，特别是化合物1-(((5S,7R)-3-(5-环丙基吡嗪-2-基)-7-羟基-2-氧代-1-氧杂-3-氮杂螺[4.5]癸烷-7-基)甲基)-1H-苯并[d]咪唑-6-甲腈、其药学上可接受的盐和含有该化合物的药物组合物。 本发明的化合物可用于治疗选自以下疾病的疾病状态：动脉粥样硬化、血管源性水肿相关疾病、手术后腹部水肿、眼部水肿、脑水肿、局部和全身性水肿、体液潴留、败血症、高血压、炎症、骨相关功能障碍和充血性心力衰竭、肺部疾病、慢性阻塞性肺病、呼吸机诱发的肺损伤、高海拔诱发的肺水肿、急性呼吸窘迫综合征、急性肺损伤、肺纤维化、鼻窦炎/鼻炎、哮喘、咳嗽；包括急性咳嗽、亚急性咳嗽和慢性咳嗽、肺动脉高压、膀胱过度活动症、膀胱炎、疼痛、运动神经元紊乱、遗传性功能增益紊乱、心血管疾病、肾功能紊乱、中风、青光眼、视网膜病变、子宫内膜异位症、早产、皮炎、瘙痒症、肝病瘙痒症、糖尿病、代谢紊乱、肥胖、偏头痛、胰腺炎、肿瘤抑制、免疫抑制、骨关节炎、克罗恩病、结肠炎、腹泻、肠道不规则（高反应性/低反应性）、大便失禁、肠易激综合征（IBS）、便秘、肠道疼痛和痉挛、乳糜泻、乳糖不耐症和胀气。