3-(4-{4-[4-((E)-2-tert-butyloxycarbonyl-vinyl)phenyl]-5-[4-(2-dodecylcarbamoyl-vinyl)phenyl]-1H-imidazol-2-yl}phenyl)-isoxazole-5-carboxylic acid ethyl ester | 274904-56-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 3-(4-{4-[4-((E)-2-tert-butyloxycarbonyl-vinyl)phenyl]-5-[4-(2-dodecylcarbamoyl-vinyl)phenyl]-1H-imidazol-2-yl}phenyl)-isoxazole-5-carboxylic acid ethyl ester
• 英文别名: ethyl 3-[4-[5-[4-[(E)-3-(dodecylamino)-3-oxoprop-1-enyl]phenyl]-4-[4-[(E)-3-[(2-methylpropan-2-yl)oxy]-3-oxoprop-1-enyl]phenyl]-1H-imidazol-2-yl]phenyl]-1,2-oxazole-5-carboxylate
• CAS: 274904-56-2
• 化学式: C₄₉H₅₈N₄O₆
• 分子量: 799.023
• InChiKey: NMWYTZAMAMZYNI-RWRHWQIFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.3
• 重原子数：
  59
• 可旋转键数：
  24
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-(4-{4-[4-((E)-2-tert-butyloxycarbonyl-vinyl)phenyl]-5-[4-(2-dodecylcarbamoyl-vinyl)phenyl]-1H-imidazol-2-yl}phenyl)-isoxazole-5-carboxylic acid ethyl ester 在 lithium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以55%的产率得到3-(4-{4-[4-((E)-2-Carboxy-vinyl)-phenyl]-5-[4-((E)-2-dodecylcarbamoyl-vinyl)-phenyl]-1H-imidazol-2-yl}-phenyl)-isoxazole-5-carboxylic acid
  参考文献：
  名称：

  Development of Potent Non-Carbohydrate Imidazole-Based Small Molecule Selectin Inhibitors with Antiinflammatory Activity

  摘要：

  A novel series of non-carbohydrate imidazole-based selectin inhibitors has been discovered via high-throughput screening using a P-selectin ELISA-based assay system. The initial lead 1 had an IC(50) of 17 muM in the P-selectin ELISA; this potency was significantly improved via an extensive SAR exploration. One of the current lead compounds (29) has an IC(50) of 300 nM in a P-selectin ELISA; it also has good activity in P- and E-selectin cell adhesion assays and shows efficacy in vivo. These compounds represent a novel series of sLe(X) mimetics with antiinflammatory activity. Their unique profile supports our interest in their further evaluation as drug candidates for the treatment of inflammation. Herein we describe the syntheses, optimization, and SAR of this series of novel potent selectin antagonists.

  DOI：

  10.1021/jm000508c
• 作为产物：
  描述：

  N-十二烷基丙烯酰胺 在 palladium diacetate 、 TEA 、 ammonium acetate 、 溶剂黄146 、 三(邻甲基苯基)磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 3-(4-{4-[4-((E)-2-tert-butyloxycarbonyl-vinyl)phenyl]-5-[4-(2-dodecylcarbamoyl-vinyl)phenyl]-1H-imidazol-2-yl}phenyl)-isoxazole-5-carboxylic acid ethyl ester
  参考文献：
  名称：

  Development of Potent Non-Carbohydrate Imidazole-Based Small Molecule Selectin Inhibitors with Antiinflammatory Activity

  摘要：

  A novel series of non-carbohydrate imidazole-based selectin inhibitors has been discovered via high-throughput screening using a P-selectin ELISA-based assay system. The initial lead 1 had an IC(50) of 17 muM in the P-selectin ELISA; this potency was significantly improved via an extensive SAR exploration. One of the current lead compounds (29) has an IC(50) of 300 nM in a P-selectin ELISA; it also has good activity in P- and E-selectin cell adhesion assays and shows efficacy in vivo. These compounds represent a novel series of sLe(X) mimetics with antiinflammatory activity. Their unique profile supports our interest in their further evaluation as drug candidates for the treatment of inflammation. Herein we describe the syntheses, optimization, and SAR of this series of novel potent selectin antagonists.

  DOI：

  10.1021/jm000508c

文献信息

• [EN] 5-MEMBERED HETEROCYCLES FOR THE TREATMENT OF HUMAN DISEASES INVOLVING MODULATORS OF SELECTINS<br/>[FR] HETEROCYCLES A 5 CHAINONS POUR LE TRAITEMENT DE MALADIES HUMAINES DANS LESQUELLES INTERVIENNENT DES MODULATEURS DE SELECTINES
  申请人：ONTOGEN CORP

  公开号：WO2000033836A1

  公开（公告）日：2000-06-15

  Compounds of formulas (1), (2) and (3) are disclosed, where at least one and no more than two of R?1, R2, R3, R4 or R5¿ are as defined in Group 1. In said formulas R1 is typically a moiety containing a terminal carboxylic acid group such as phenoxy acetic acid, R2 is typically a hydrophobic moiety such as functionalized alkyl chain or a functionalized aryl group, and R3 is typically a functionalized aryl group, and they are within the scope of this invention. These compounds exhibit inhibitory activity against the Selectins and are indicated in the treatment of human diseases involving Selectins.
• Development of Potent Non-Carbohydrate Imidazole-Based Small Molecule Selectin Inhibitors with Antiinflammatory Activity
  作者：Deborah H. Slee、Suzanne J. Romano、Jinghua Yu、Truc N. Nguyen、Judy K. John、Neil K. Raheja、Frank U. Axe、Todd K. Jones、William C. Ripka

  DOI：10.1021/jm000508c

  日期：2001.6.1

  A novel series of non-carbohydrate imidazole-based selectin inhibitors has been discovered via high-throughput screening using a P-selectin ELISA-based assay system. The initial lead 1 had an IC(50) of 17 muM in the P-selectin ELISA; this potency was significantly improved via an extensive SAR exploration. One of the current lead compounds (29) has an IC(50) of 300 nM in a P-selectin ELISA; it also has good activity in P- and E-selectin cell adhesion assays and shows efficacy in vivo. These compounds represent a novel series of sLe(X) mimetics with antiinflammatory activity. Their unique profile supports our interest in their further evaluation as drug candidates for the treatment of inflammation. Herein we describe the syntheses, optimization, and SAR of this series of novel potent selectin antagonists.