N-cyclopentyl-4-[(2-pyrazin-2-ylphenyl)methyl]-3,5-dihydro-2H-1,4-benzoxazepine-5-carboxamide

• 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-cyclopentyl-4-[(2-pyrazin-2-ylphenyl)methyl]-3,5-dihydro-2H-1,4-benzoxazepine-5-carboxamide
• 化学式: C₂₆H₂₈N₄O₂
• 分子量: 428.5
• InChiKey: ZZDCCCQQGVTYPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  67.4
• 氢给体数：
  1
• 氢受体数：
  5

文献信息

• STIMULATORS OF INCRETIN HORMONES SECRETION, METHOD FOR PREPARATION AND USE THEREOF
  申请人：Savchuk Nikolay Filippovich

  公开号：US20140100216A1

  公开（公告）日：2014-04-10

  The invention relates to the area of medicinal chemistry, pharmacology and medicine and includes description of pharmaceutical compositions and combined medicaments on the base of secretion stimulators and protectors of incretin hormones for treatment of metabolic diseases (among them, diabetes, obesity, metabolic syndrome and the like). The invention consists in that that pharmaceutical composition or combined medicament comprises a derivative of tetrahydrobenzo[f][1,4]oxazepine—either nonsteroidal agonist of bile aids receptor TGR5, or one of endogenous bile acids which stimulate incretin hormones secretion, and also one of the known inhibitors of DPP-IV proteinase. In this case administration of TGR5 agonists is carried out peroral, and administration of endogenous bile acids is exercised rectal in the form of suppository or gel. As proteinase DPP-IV inhibitors could be used Vildagliptin, Saxagliptin, Sitagliptin, Teneligliptin, Linagliptin, Dutogliptin, Alogliptin, Gemigliptin, Carmegliptin and the like. Besides, the invention includes description of novel tetrahydrobenzo[f][1,4]oxazepine derivatives—nonsteroidal agonist of bile aids receptors TGR5, and also methods for their preparation. The invention provides enhancement of therapy effectiveness owing to synergetic action of the components, thus making possible simultaneous treatment of diabetes, and obesity, other metabolic diseases and their cardiovascular and renal complications.

  本发明涉及药物化学、药理学和医学领域，包括药物组合物和基于促进肠促素激素分泌的保护剂的药物组合物的描述，用于治疗代谢性疾病（其中包括糖尿病、肥胖症、代谢综合征等）。该发明在于药物组合物或联合药物包括四氢苯并[f][1,4]噁唑啉的衍生物——非类固醇胆汁酸受体TGR5激动剂，或者其中一种刺激肠促素激素分泌的内源性胆汁酸，以及已知的DPP-IV蛋白酶抑制剂之一。在这种情况下，TGR5激动剂的给药是经口的，内源性胆汁酸的给药是通过栓剂或凝胶进行直肠给药。作为蛋白酶DPP-IV抑制剂，可以使用维拉利普汀、萨格利普汀、西他列汀、替格列汀、林格列汀、杜托列汀、阿洛列汀、吉美列汀、卡美列汀等。此外，本发明还包括新的四氢苯并[f][1,4]噁唑啉衍生物——非类固醇胆汁酸受体TGR5激动剂以及其制备方法的描述。本发明通过组分的协同作用提高了治疗效果，从而使糖尿病、肥胖症、其他代谢性疾病及其心血管和肾脏并发症能够同时治疗。