马西替坦杂质7 | 1433875-14-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 马西替坦杂质7
• 英文名称: ACT-373898
• 英文别名: 2-((5-(4-bromophenyl)-6-((N-propylsulfamoyl)amino)pyrimidin-4-yl)oxy)acetic acid；Macitentan metabolite M5；2-[5-(4-bromophenyl)-6-(propylsulfamoylamino)pyrimidin-4-yl]oxyacetic acid
• CAS: 1433875-14-9
• 化学式: C₁₅H₁₇BrN₄O₅S
• 分子量: 445.294
• InChiKey: IMSGHDWVBCDHNU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-[5-(4-溴苯基)-6-(2-羟基乙氧基)-4-嘧啶基]-N'-丙基氨基磺酰胺 在 Jones reagent 作用下， 以 丙酮 为溶剂， 反应 18.0h， 以45%的产率得到马西替坦杂质7
  参考文献：
  名称：

  The metabolism of the dual endothelin receptor antagonist macitentan in rat and dog

  摘要：

  1.The metabolism of the endothelin receptor antagonist macitentan has been characterized in bile duct-cannulated rats and dogs.2.In both species, macitentan was metabolized along five primary pathways, i.e. conjugation with glucose (M9), oxidative depropylation (M6), aliphatic hydroxylation (M7), oxidative cleavage of the ethylene glycol linker (M4) and hydrolysis of the sulfamide moiety (M3). Most of the primary metabolites underwent subsequent biotransformation including conjugation with glucuronic acid or glucose, hydrolysis of the sulfamide group or secondary oxidation of the ethylene glycol moiety.3.Though there were species differences in their relative importance, all metabolic pathways were present in rat and dog. The depropylated M6 was the only metabolite present in plasma of both species.4.Metabolism was a prerequisite for macitentan excretion as relevant amounts of parent drug were neither detected in bile nor urine. Biliary excretion was the major elimination pathway, while renal elimination was of little importance.

  DOI：

  10.3109/00498254.2015.1070302

文献信息

• [EN] MACITENTAN FOR USE IN TREATING PORTOPULMONARY HYPERTENSION<br/>[FR] MACITENTAN DESTINÉ À ÊTRE UTILISÉ DANS LE TRAITEMENT DE L'HYPERTENSION PORTOPULMONAIRE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2020201479A1

  公开（公告）日：2020-10-08

  The present invention provides methods for treating portopulmonary hypertension, comprising administering to a patient in need thereof, a therapeutically effective amount of macitentan. Preferably, the methods are clinically proven safe and/or effective. Also provided are methods of improving liver transplant perioperative mortality risk category, improving MELD exception eligibility, and reducing the risk of removal from a liver transplant waitlist in a patient with portopulmonary hypertension and liver disease, comprising administering to a patient in need thereof a therapeutically effective amount of macitentan.