艾多南坦 | 210891-04-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 艾多南坦
• 英文名称: Edonentan
• 英文别名: N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2 oxazolyl) [1,1'-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide；N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide；N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[,1'-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide；BMS207940；N-[[2-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-N,3,3-trimethylbutanamide
• CAS: 210891-04-6
• 化学式: C₂₈H₃₂N₄O₅S
• 分子量: 536.652
• InChiKey: ORJRYNKVKJAJPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-溴苯磺酰氯 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 正丁基锂 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 sodium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 正戊烷 为溶剂， 反应 16.42h， 生成 艾多南坦
  参考文献：
  名称：

  Biphenylsulfonamide Endothelin Receptor Antagonists. 4. Discovery of N-[[2‘-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1‘-biphenyl]- 2-yl]methyl]-N,3,3-trimethylbutanamide (BMS-207940), A Highly Potent and Orally Active ET_A Selective Antagonist

  摘要：

  We have previously disclosed the selective ETA receptor antagonist N-(3,4-dimethyl-5-isoxazolyl)-4'-(2-oxazolyl)[1,1'-biphenyl]-2-sulfonamide (1, BMS-193884) as a clinical development candidate. Additional SAR studies at the 2'-position of 1 led to the identification of several analogues with improved binding affinity as well as selectivity for the ETA receptor. Following the discovery that a 3-amino-isoxazole group displays significantly improved metabolic stability in comparison to its 5-regioisomer, the 3-amino-isoxazole group was combined with the optimal 2'-substituent lleading to 16a (BMS-207940). Compound 16a is an extremely potent (ETAKi = 10 pM) and selective (80000-fold for ETA vs ETB) antagonist. It is also 150-fold more potent and >6-fold more selective than 1. The bioavailability of 16a was 100% in rats and the systemic clearance and volume of distribution are higher than that of 1. In rats, intravenous 16a blocks big ET pressor responses with 30-fold greater potency than 1. After oral dosing at 3 mumol/kg, 16a displays enhanced duration relative to 1.

  DOI：

  10.1021/jm020289q

文献信息

• Methods for the preparation of biphenyl isoxazole sulfonamides
  申请人：——

  公开号：US20020132838A1

  公开（公告）日：2002-09-19

  Methods for the preparation of biphenyl isoxazole sulfonamides and intermediates thereof. The present invention also relates to the novel intermediates prepared by these methods. The biphenyl isoxazole sulfonamides prepared by the present methods are endothelin antagonists useful, inter alia, for the treatment of hypertension.

  本发明涉及制备联苯基异噁唑磺酰胺及其中间体的方法。本发明还涉及通过这些方法制备的新中间体。本发明所制备的联苯基异噁唑磺酰胺是内皮素拮抗剂，可用于治疗高血压等病症。
• [EN] ENDOTHELIN ANTAGONISTS: N-[[2'-[ [(4,5-DIMETHYL-3-ISOXAZOLYL) AMINO]SULFONYL]-4-(2-OXAZOLYL) [1,1'-BIPHENYL]-2-YL]METHYL] -N,3,3-TRIMETHYLBUTANAMIDE AND N-(4,5-DIMETHYL-3-ISOXAZOLYL) -2'-[(3,3-DIMETHYL-2-OXO-1-PYRROLIDINYL) METHYL] -4'-(2-OXAZOLYL)[1,1'-BIPHENYL]-2-SULFONAMIDE AND SALTS THEREOF<br/>[FR] ANTAGONISTES DE L'ENDOTHELINE: N-[[2'-[[4,5-DIMETHYL-3-ISOXAZOLYL)AMINO]SULFONYL]-4-(2-OXAZOLYL)[1,1'-BIPHENYL]-2-YL]METHYL]-N,3,3-TRIMETHYLBUTANAMIDE ET N-(4,5-DIMETHYL-3-ISOXAZOLYL)-2'-[3,3-DIMETHYL-2-OXO-1-PYRROLIDINYL)METHYL]-4'-(2-OXAZOLYL)[1,1'-BIPHENYL]-2-SULFONAMIDE ET LEURS SELS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：WO1998033780A1

  公开（公告）日：1998-08-06

  (EN) The compounds N-[[2'-[ [(4,5-dimethyl-3-isoxazolyl) amino]sulfonyl]-4-(2-oxazolyl) [1,1'-biphenyl]-2-yl]methyl]-N, 3,3-trimethylbutanamide and N-(4,5-dimethyl-3-isoxazolyl)-2'-[ (3,3-dimethyl-2-oxo-1-pyrrolidinyl) methyl]-4'-(2-oxazolyl) [1,1'-biphenyl]-2-sulfonamide, and salts thereof, useful as endothelin antagonists.(FR) Les composés N-[[2'-[[4,5-diméthyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphényl]-2-yl]méthyl]-N,3,3-triméthylbutanamide et N-(4,5-diméthyl-3-isoxazolyl)-2'-[3,3-diméthyl-2-oxo-1-pyrrolidinyl)méthyl]-4'-(2-oxazolyl)[1,1'-biphényl]-2-sulfonamide, et leurs sels, sont utiles comme antagonistes de l'endothéline.

  这些化合物是N-[[2'-[[(4,5-二甲基-3-异噁唑基)氨基]磺酰]-4-(2-噁唑基)[1,1'-联苯基]-2-基]甲基]-N,3,3-三甲基丁酰胺和N-(4,5-二甲基-3-异噁唑基)-2'-[(3,3-二甲基-2-氧代-1-吡咯烷基)甲基]-4'-(2-噁唑基)[1,1'-联苯基]-2-磺酰胺，及其盐，可用作内皮素拮抗剂。
• Isoxazolyl endothelin antagonists
  申请人：Bristol-Myers Squibb Co.

  公开号：US06043265A1

  公开（公告）日：2000-03-28

  The compounds N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-bi phenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide and N-(4,5-dimethyl-3-isoxazolyl)-2'-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methy l]-4'-(2-oxazolyl)[1,1'-biphenyl]-2-sulfonamide, and salts thereof, useful as endothelin antagonists.

  化合物N-[[2'-[[(4,5-二甲基-3-异噁唑基)氨基]磺酰]-4-(2-噁唑基)[1,1'-联苯基]-2-基]甲基]-N,3,3-三甲基丁酰胺和N-(4,5-二甲基-3-异噁唑基)-2'-[(3,3-二甲基-2-氧代-1-吡咯烷基)甲基]-4'-(2-噁唑基)[1,1'-联苯基]-2-磺酰胺及其盐，可用作内皮素拮抗剂。
• Method for preventing or treating pain by administering an endothelin antagonist
  申请人：——

  公开号：US20020082285A1

  公开（公告）日：2002-06-27

  Prevention or treatment of pain by administration of an endothelin antagonist.

  通过服用内皮素拮抗剂预防或治疗疼痛。
• Method for preventing or treating pulmonary inflammation by administering an endothelin antagonist
  申请人：——

  公开号：US20030004199A1

  公开（公告）日：2003-01-02

  Prevention or treatment of disorders of chronic or acute pulmonary inflammation by administration of an endothelin antagonist.

  通过服用内皮素拮抗剂预防或治疗慢性或急性肺部炎症。