2(R)-{2-[4-(3-thienyl)phenyl]ethyl}-4(S)-butylpentanedioic acid 5-tert-butyl ester | 187827-30-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2(R)-{2-[4-(3-thienyl)phenyl]ethyl}-4(S)-butylpentanedioic acid 5-tert-butyl ester
• 英文别名: (2R,4S)-4-[(2-methylpropan-2-yl)oxycarbonyl]-2-[2-(4-thiophen-3-ylphenyl)ethyl]octanoic acid
• CAS: 187827-30-1
• 化学式: C₂₅H₃₄O₄S
• 分子量: 430.609
• InChiKey: QEXCPIFFIGGJQR-RTWAWAEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  30
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  91.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2(R)-{2-[4-(3-thienyl)phenyl]ethyl}-4(S)-butylpentanedioic acid 5-tert-butyl ester 在 N-甲基吗啉 、 1-羟基苯并三唑 、 苯甲醚 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (2S,4R)-2-Butyl-4-((S)-2,2-dimethyl-1-methylcarbamoyl-propylcarbamoyl)-6-(4-thiophen-3-yl-phenyl)-hexanoic acid
  参考文献：
  名称：

  Inhibition of Stromelysin-1 (MMP-3) by P₁‘-Biphenylylethyl Carboxyalkyl Dipeptides

  摘要：

  Carboxyalkyl peptides containing a biphenylylethyl group at the P-1' position were found to be potent inhibitors of stromelysin-1 (MMP-3) and gelatinase A (MMP-2), in the range of 10-50 nM, but poor inhibitors of collagenase (MMP-1). Combination of a biphenylylethyl moiety at P-1', a tert-butyl group at P-2', and a methyl group at P-3' produced orally bioavailable inhibitors as measured by an in vivo model of MMP-3 degradation of radiolabeled transferrin in the mouse pleural cavity. The X-ray structure of a complex of a P-1'-biphenyl inhibitor and the catalytic domain of MMP-3 is described. Inhibitors that contained halogenated biphenylylethyl residues at P-1' proved to be superior in terms of enzyme potency and oral activity with 2(R)-[2-(4'-fluoro-4-biphenylyl)ethyl]-4(S)-n-butyl -1,5-pentanedioic acid 1-(alpha(S)-tert-butylglycine methylamide) amide (L-758,354, 26) having a K-i of 10 nM against MMP-3 and an ED(50) of 11 mg/kg po in the mouse pleural cavity assay. This compound was evaluated in acute (MMP-3 and IL-1 beta injection in the rabbit) and chronic (rat adjuvant-induced arthritis and mouse collagen-induced arthritis) models of cartilage destruction but showed activity only in the MMP-3 injection model (ED(50) = 6 mg/kg iv).

  DOI：

  10.1021/jm960465t
• 作为产物：
  描述：

  4-(P-碘苯基)丁酸 在 titanium(IV) isopropylate 、 4-二甲氨基吡啶 、 N,N-二甲基丙烯基脲 、 lithium hydroxide 、 四(三苯基膦)钯 、 正丁基锂 、 四丁基氟化铵 、 双氧水 、 四氯化钛 、 碳酸氢钠 、 sodium carbonate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 potassium bromide 、 sodium sulfite 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 19.5h， 生成 2(R)-{2-[4-(3-thienyl)phenyl]ethyl}-4(S)-butylpentanedioic acid 5-tert-butyl ester
  参考文献：
  名称：

  Inhibition of Stromelysin-1 (MMP-3) by P₁‘-Biphenylylethyl Carboxyalkyl Dipeptides

  摘要：

  Carboxyalkyl peptides containing a biphenylylethyl group at the P-1' position were found to be potent inhibitors of stromelysin-1 (MMP-3) and gelatinase A (MMP-2), in the range of 10-50 nM, but poor inhibitors of collagenase (MMP-1). Combination of a biphenylylethyl moiety at P-1', a tert-butyl group at P-2', and a methyl group at P-3' produced orally bioavailable inhibitors as measured by an in vivo model of MMP-3 degradation of radiolabeled transferrin in the mouse pleural cavity. The X-ray structure of a complex of a P-1'-biphenyl inhibitor and the catalytic domain of MMP-3 is described. Inhibitors that contained halogenated biphenylylethyl residues at P-1' proved to be superior in terms of enzyme potency and oral activity with 2(R)-[2-(4'-fluoro-4-biphenylyl)ethyl]-4(S)-n-butyl -1,5-pentanedioic acid 1-(alpha(S)-tert-butylglycine methylamide) amide (L-758,354, 26) having a K-i of 10 nM against MMP-3 and an ED(50) of 11 mg/kg po in the mouse pleural cavity assay. This compound was evaluated in acute (MMP-3 and IL-1 beta injection in the rabbit) and chronic (rat adjuvant-induced arthritis and mouse collagen-induced arthritis) models of cartilage destruction but showed activity only in the MMP-3 injection model (ED(50) = 6 mg/kg iv).

  DOI：

  10.1021/jm960465t