2(R)-(mercaptomethyl)butanoic acid | 147936-77-4

• 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)-(mercaptomethyl)butanoic acid
• 英文别名: (2R)-2-(sulfanylmethyl)butanoic acid
• CAS: 147936-77-4
• 化学式: C₅H₁₀O₂S
• 分子量: 134.199
• InChiKey: GOSBUVMCOAWATC-BYPYZUCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  38.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  <1-(4-chlorobenzyl)-4-methyl-6-<(5-phenylpyridin-2-yl)methoxy>-4,5-dihydro-1H-thiopyrano<2,3,4-cd>indol-2-yl>methanol 、 2(R)-(mercaptomethyl)butanoic acid 在 三氟化硼乙醚 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 0.05h， 以71%的产率得到3-[({1-(4-chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)methoxy]-4,5-dihydro-1H-thiopyrano(2,3,4-cd)indol-2-yl}methyl)thio]-2(R)-ethylpropanoic acid
  参考文献：
  名称：

  Thiopyrano[2,3,4-cd]indoles as 5-Lipoxygenase Inhibitors: Synthesis, Biological Profile, and Resolution of 2-[2-[1-(4-Chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)methoxy]-4,5-dihydro-1H-thiopyrano[2,3,4-cd]indol-2-yl]ethoxy]butanoic Acid

  摘要：

  Leukotriene biosynthesis inhibitors have potential as new therapies for asthma and inflammatory diseases. The recently disclosed thiopyrano[2,3,4-cd] indole class of 5-lipoxygenase (5-LO) inhibitors has been investigated with particular emphasis on the side chain bearing the acidic functionality. The SAR studies have shown that the inclusion of a heteroatom (O or S) in conjunction with an alpha-ethyl substituted acid leads to inhibitors of improved potency. The most potent inhibitor prepared contains a 2-ethoxybutanoic acid side chain. This compound, 14d (2-[2-[1-(4-chlorobenzyl)-4-methyl-6-[ (5-phenylpyridin-2-yl)methoxy]-4,5-dihydro-1H-thiopyrano[2,3,4-cd]indol-2-yl]ethoxy]-butanoic acid, L-699,333), inhibits 5-HPETE production by human 5-LO and LTB(4) biosynthesis by human PMN leukocytes and human whole blood (IC(50)s Of 22 nM, 7 nM and 3.8 mu M, respectively). The racemic acid 14d has been shown to be functionally active in a rat pleurisy model (inhibition of LTB(4), ED(50) = 0.65 mg/kg, 6 h pretreatment) and in the hyperreactive rat model of antigen-induced dyspnea(50% inhibition at 2 and 4 h pretreatment; 0.5 mg/kg po). In addition, 14d shows excellent functional activity against antigen-induced bronchoconstriction in the conscious squirrel monkey [89% inhibition of the increase in R(L) and 68% inhibition in the decrease in C-dyn (0.1 mg/kg, n = 3)] and in the conscious sheep models of asthma (iv infusion at 2.5 mu g/kg/min). Acid 14d is highly selective as an inhibitor of 5-LO activity when compared to the inhibition of human 15-LO, porcine 12-LO and ram seminal vesicle cyclooxygenase (IC50 > 5 mu M) Or competition in a FLAP binding assay (IC5O > 10 mu M). Resolution of 14d affords 14g, the most potent diastereomer, which inhibits the 5-HPETE production of human 5-LO and LTB(4) biosynthesis of human PMN leukocytes and human whole blood with IC(50)s Of 8 nM, 4 nM, and 1 mu M respectively. The in vitro and in vivo profile of 14d is comparable to that of MK-0591, which has showed biochemical efficacy in inhibiting ex vivo LTB(4) biosynthesis and urinary LTE(4) excretion in clinical trials.

  DOI：

  10.1021/jm00034a013
• 作为产物：
  描述：

  在 氨 、 氢溴酸 、 sodium 、 溶剂黄146 作用下， 反应 6.5h， 生成 2(R)-(mercaptomethyl)butanoic acid
  参考文献：
  名称：

  Thiopyrano[2,3,4-cd]indoles as 5-Lipoxygenase Inhibitors: Synthesis, Biological Profile, and Resolution of 2-[2-[1-(4-Chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)methoxy]-4,5-dihydro-1H-thiopyrano[2,3,4-cd]indol-2-yl]ethoxy]butanoic Acid

  摘要：

  Leukotriene biosynthesis inhibitors have potential as new therapies for asthma and inflammatory diseases. The recently disclosed thiopyrano[2,3,4-cd] indole class of 5-lipoxygenase (5-LO) inhibitors has been investigated with particular emphasis on the side chain bearing the acidic functionality. The SAR studies have shown that the inclusion of a heteroatom (O or S) in conjunction with an alpha-ethyl substituted acid leads to inhibitors of improved potency. The most potent inhibitor prepared contains a 2-ethoxybutanoic acid side chain. This compound, 14d (2-[2-[1-(4-chlorobenzyl)-4-methyl-6-[ (5-phenylpyridin-2-yl)methoxy]-4,5-dihydro-1H-thiopyrano[2,3,4-cd]indol-2-yl]ethoxy]-butanoic acid, L-699,333), inhibits 5-HPETE production by human 5-LO and LTB(4) biosynthesis by human PMN leukocytes and human whole blood (IC(50)s Of 22 nM, 7 nM and 3.8 mu M, respectively). The racemic acid 14d has been shown to be functionally active in a rat pleurisy model (inhibition of LTB(4), ED(50) = 0.65 mg/kg, 6 h pretreatment) and in the hyperreactive rat model of antigen-induced dyspnea(50% inhibition at 2 and 4 h pretreatment; 0.5 mg/kg po). In addition, 14d shows excellent functional activity against antigen-induced bronchoconstriction in the conscious squirrel monkey [89% inhibition of the increase in R(L) and 68% inhibition in the decrease in C-dyn (0.1 mg/kg, n = 3)] and in the conscious sheep models of asthma (iv infusion at 2.5 mu g/kg/min). Acid 14d is highly selective as an inhibitor of 5-LO activity when compared to the inhibition of human 15-LO, porcine 12-LO and ram seminal vesicle cyclooxygenase (IC50 > 5 mu M) Or competition in a FLAP binding assay (IC5O > 10 mu M). Resolution of 14d affords 14g, the most potent diastereomer, which inhibits the 5-HPETE production of human 5-LO and LTB(4) biosynthesis of human PMN leukocytes and human whole blood with IC(50)s Of 8 nM, 4 nM, and 1 mu M respectively. The in vitro and in vivo profile of 14d is comparable to that of MK-0591, which has showed biochemical efficacy in inhibiting ex vivo LTB(4) biosynthesis and urinary LTE(4) excretion in clinical trials.

  DOI：

  10.1021/jm00034a013