N-(3,4-Dimethyl-5-isoxazolyl)-4'-(2-pyridinyl)[1,1'-biphenyl]-2-sulfonamide | 181132-99-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3,4-Dimethyl-5-isoxazolyl)-4'-(2-pyridinyl)[1,1'-biphenyl]-2-sulfonamide
• 英文别名: 4''-Pyridin-2-yl-biphenyl-2-sulfonic acid (3,4-dimethyl-isoxazol-5-yl)-amide；N-(3,4-dimethyl-1,2-oxazol-5-yl)-2-(4-pyridin-2-ylphenyl)benzenesulfonamide
• CAS: 181132-99-0
• 化学式: C₂₂H₁₉N₃O₃S
• 分子量: 405.477
• InChiKey: DGNMDJFSXFSHGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  93.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(3,4-Dimethyl-5-isoxazolyl)-4'-(2-pyridinyl)[1,1'-biphenyl]-2-sulfonamide 在 间氯过氧苯甲酸 作用下， 生成 4''-(1-Oxy-pyridin-2-yl)-biphenyl-2-sulfonic acid (3,4-dimethyl-isoxazol-5-yl)-amide
  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：

  2-borono-N-(3,4-dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]-benzenesulfonamide 在 盐酸 、 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)-4'-(2-pyridinyl)[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：EP0725067A1

  公开（公告）日：1996-08-07

  Compounds of the formula 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.

  式中化合物 抑制内皮素的活性。符号定义如下： R1 和 R2 各自直接与一个环碳键结合，且各自独立地 (a) 氢 (b) 烷基或烷氧基 (c) 羟基 (d) 卤；或 (e) 氨基； R3 和 R4 各自直接与一个环碳键结合，且各自独立存在 (a) 氢 (b) 烷基烯基、炔基、烷氧基、环烷基、环烷基烷基、环烯基、环炔基烷基、芳基、芳氧基、芳烷基或芳烷氧基，其中任何一个可被 Z1、Z2 和 Z3 取代； (c) 卤 (d) 羟基 (e) 氰基 (f) 硝基 (g) -C(O)H 或 -C(O)R5 (h) -CO2H或-CO2R5； (i) -Z4-NR6R7 (j) -Z4-N(R10)-Z5-NR8R9; 或 (k) R3 和 R4 也可以是亚烷基或烯基，其中任一亚烷基或烯基可被 Z1、Z2 和 Z3 取代，与它们所连接的碳原子一起组成一个 4 至 8 元饱和、不饱和或芳香环； 其余符号如说明书中所定义。
• 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.
• [EN] PHARMACEUTICAL AND VETERINARY USES OF ENDOTHELIN ANTAGONISTS<br/>[FR] UTILISATIONS PHARMACEUTIQUES ET VETERINAIRES D'ANTAGONISTES DE L'ENDOTHELINE ET APPLICATIONS ASSOCIEES
  申请人：TEXAS BIOTECHNOLOGY CORP

  公开号：WO2001049289A1

  公开（公告）日：2001-07-12

  Pharmaceutical and veterinary uses of endothelin antagonists are provided. In particular, methods of treatment of laminitis, such as equine and bovine laminitis, by administration of one or more endothelin antagonists are provided. Methods of treatment, prevention, or amelioration of one or more symptoms of menopause; osteoporosis and metabolic bone disorders; climacteric disorders including hot flushes or flashes, abnormal clotting patterns, urogenital discomfort and increased incidence of cardiovascular disease, and other disorders associated with the reduction in ovarian function in women; pre-eclampsia; and control and management of labor during pregnancy by administration of endothelin antagonists are also provided.