N-(3,4-Dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]-4'-(4-pyrimidinyl)[1,1'-biphenyl]-2-sulfonamide | 181133-22-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-(3,4-Dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]-4'-(4-pyrimidinyl)[1,1'-biphenyl]-2-sulfonamide
• 英文别名: N-(3,4-dimethyl-1,2-oxazol-5-yl)-N-(2-methoxyethoxymethyl)-2-(4-pyrimidin-4-ylphenyl)benzenesulfonamide
• CAS: 181133-22-2
• 化学式: C₂₅H₂₆N₄O₅S
• 分子量: 494.571
• InChiKey: ATFPRYZSMFZVRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  116
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(3,4-Dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]-4'-(4-pyrimidinyl)[1,1'-biphenyl]-2-sulfonamide 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 N-(3,4-Dimethyl-5-isoxazolyl)-4'-(4-pyrimidinyl)[1,1'-biphenyl]-2-sulfonamide
  参考文献：
  名称：

  Biphenylsulfonamide Endothelin Receptor Antagonists. Part 3: Structure–Activity Relationship of 4′-Heterocyclic Biphenylsulfonamides

  摘要：

  A number of 4'-heterocyclic biphenylsulfonamide derivatives, formally derived from BMS-193884 (1) by replacing the oxazole ring with other heterocyclic rings, are potent and selective endothelin A (ETA) receptor antagonists. Among the analogues examined, the pyrimidine derivative 18 is the most potent (K-i = 0.9 nM) and selective for the ETA receptor, approximately equivalent to 1. (C) 2002 Bristol-Myers Squibb Company. Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00791-0
• 作为产物：
  描述：

  (9CI)-4-(4-溴苯基)-嘧啶 、 2-borono-N-(3,4-dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]-benzenesulfonamide 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 生成 N-(3,4-Dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]-4'-(4-pyrimidinyl)[1,1'-biphenyl]-2-sulfonamide
  参考文献：
  名称：

  Biphenylsulfonamide Endothelin Receptor Antagonists. Part 3: Structure–Activity Relationship of 4′-Heterocyclic Biphenylsulfonamides

  摘要：

  A number of 4'-heterocyclic biphenylsulfonamide derivatives, formally derived from BMS-193884 (1) by replacing the oxazole ring with other heterocyclic rings, are potent and selective endothelin A (ETA) receptor antagonists. Among the analogues examined, the pyrimidine derivative 18 is the most potent (K-i = 0.9 nM) and selective for the ETA receptor, approximately equivalent to 1. (C) 2002 Bristol-Myers Squibb Company. Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00791-0

文献信息

• Substituted biphenyl sulfonamide endothelin antagonists
  申请人：Bristol-Myers Squibb Company

  公开号：US05760038A1

  公开（公告）日：1998-06-02

  Compounds of the formula ##STR1## in which the symbols are as defined herein, inhibit the activity of endothelin.

  式子为##STR1##的化合物，其中符号如本文所定义，可抑制内皮素的活性。
• US5780473A
  申请人：——

  公开号：US5780473A

  公开（公告）日：1998-07-14
• US5760038A
  申请人：——

  公开号：US5760038A

  公开（公告）日：1998-06-02
• [EN] SUBSTITUTED BIPHENYL SULFONAMIDE ENDOTHELIN ANTAGONISTS<br/>[FR] ANTAGONISTES DE L'ENDOTHELINE A BASE DE BIPHENYL-SULFONAMIDES SUBSTITUES
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：WO1998004260A1

  公开（公告）日：1998-02-05

  (EN) Compounds of formula (I) inhibit the activity of endothelin. The symbols are defined as follows: R1 and R2 are each directly bonded to a ring carbon and are each independently (a) hydrogen; (b) alkyl or alkoxy; (c) hydroxyl; (d) halo; or (e) amino; R3 and R4 are each directly bonded to a ring carbon and are each independently (a) hydrogen; (b) alkyl alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted with Z1, Z2 and Z3; (c) halo; (d) hydroxyl; (e) cyano; (f) nitro; (g) -C(O)H or -C(O)R5; (h) -CO2H or -CO2R5; (i) -Z4-NR6R7; (j) -Z4-N(R10)-Z5-NR8R9; or (k) R3 and R4 together may also be alkylene or alkenylene, either of which may be substituted with Z1, Z2 and Z3, completing a 4- to 8-membered saturated, unsaturated or aromatic ring together with the carbon atoms to which they are attached; and the remaining symbols are as defined in the specification.(FR) Les composés représentés par la formule (I) inhibent l'activité de l'endothéline. La définition des symboles utilisés dans cette formule est la suivante: R1 et R2 sont chacun directement liés à un carbone cyclique et sont chacun indépendamment (a) hydrogène, (b) alkyle ou alcoxy, (c) hydroxyle, (d) halo ou (e) amino; R3 et R4 sont chacun directement liés à un carbone cyclique et sont chacun indépendamment (a) hydrogène, (b) alkyl-alkényle, alkynyle, alcoxy, cycloalkyle, cycloalkylalkyle, cycloalkényle, cycloalkénylalkyle, aryle, aryloxy, aralkyle ou aralcoxy, chacun de ces composés pouvant être substitué par Z1, Z2 et Z3, (c) halo, (d) hydroxyle, (e) cyano, (f) nitro, (g) -C(O)H ou -C(O)R5, (h) -CO2H ou -CO2R5, (i) -Z4-NR6R7, (j) -Z4-N(R10)-Z5-NR8R9 ou (k) R3 et R4 peuvent également être ensemble alkylène ou alkénylène, chacun de ces composés pouvant être substitué par Z1, Z2 et Z3, complétant ainsi un noyau aromatique, saturé ou insaturé comportant de 4 à 8 éléments avec les atomes de carbone auxquels ils sont fixés, les autres symboles étant définis dans le descriptif de l'invention.
• Biphenylsulfonamide Endothelin Receptor Antagonists. Part 3: Structure–Activity Relationship of 4′-Heterocyclic Biphenylsulfonamides
  作者：Natesan Murugesan、Zhengxiang Gu、Philip D. Stein、Steven Spergel、Sharon Bisaha、Eddie C.-K. Liu、Rongan Zhang、Maria L. Webb、Suzanne Moreland、Joel C. Barrish

  DOI：10.1016/s0960-894x(01)00791-0

  日期：2002.2

  A number of 4'-heterocyclic biphenylsulfonamide derivatives, formally derived from BMS-193884 (1) by replacing the oxazole ring with other heterocyclic rings, are potent and selective endothelin A (ETA) receptor antagonists. Among the analogues examined, the pyrimidine derivative 18 is the most potent (K-i = 0.9 nM) and selective for the ETA receptor, approximately equivalent to 1. (C) 2002 Bristol-Myers Squibb Company. Published by Elsevier Science Ltd. All rights reserved.