3-<1-oxo-2(S)-<<(phenylmethyl)thio>methyl>butyl>-4(S)-(1-methylethyl)-2-oxazolidinone | 142542-55-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 3-<1-oxo-2(S)-<<(phenylmethyl)thio>methyl>butyl>-4(S)-(1-methylethyl)-2-oxazolidinone
• 英文别名: 3-(1-oxo-2(S)-{[(phenylmethyl)thio]methyl}butyl)-4(S)-(1-methylethyl)-2-oxazolidinone；3-(1-Oxo-2-(S)-(((phenylmethyl)thio)methyl)butyl)-4-(S)-(1-methylethyl)-2-oxazolidinone；(4S)-3-[(2S)-2-(benzylsulfanylmethyl)butanoyl]-4-propan-2-yl-1,3-oxazolidin-2-one
• CAS: 142542-55-0
• 化学式: C₁₈H₂₅NO₃S
• 分子量: 335.467
• InChiKey: LSUPQXPSNGBENM-HZPDHXFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  71.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-<1-oxo-2(S)-<<(phenylmethyl)thio>methyl>butyl>-4(S)-(1-methylethyl)-2-oxazolidinone 在 正丁基锂 、 氨 、 氢溴酸 、 sodium 、 溶剂黄146 作用下， 反应 8.75h， 生成 2(S)-(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
• 作为产物：
  描述：

  (S)-4-异丙基-2-唑烷酮 在 正丁基锂 、 二异丙胺 作用下， 反应 3.0h， 生成 3-<1-oxo-2(S)-<<(phenylmethyl)thio>methyl>butyl>-4(S)-(1-methylethyl)-2-oxazolidinone
  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

文献信息

• Fluorinated hydroxyalkylquinoline acids as leukotriene antagonists
  申请人：Merck Frosst Canada, Inc.

  公开号：US05270324A1

  公开（公告）日：1993-12-14

  Compounds having the formula I: ##STR1## are leukotriene antagonists and inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection.

  具有I式的化合物：##STR1## 是白三烯拮抗剂和白三烯生物合成抑制剂。这些化合物可用作抗哮喘，抗过敏，抗炎和细胞保护剂。它们还可用于治疗心绞痛，脑血管痉挛，肾小球肾炎，肝炎，内毒素血症，葡萄膜炎和移植排斥。
• Thiopyrano (2,3,4-c,d) indoles as inhibitors of leukotriene biosynthesis
  申请人：MERCK FROSST CANADA INC.

  公开号：EP0518426A1

  公开（公告）日：1992-12-16

  Compounds having the formula I: are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, psoriasis, uveitis and allograft rejection and in preventing the formation of atherosclerotic plaques.

  具有式 I 的化合物： 是白三烯生物合成的抑制剂。这些化合物可用作抗哮喘、抗过敏、抗炎和细胞保护剂。它们还可用于治疗心绞痛、脑痉挛、肾小球肾炎、肝炎、内毒素血症、银屑病、葡萄膜炎和异体移植排斥反应，以及预防动脉粥样硬化斑块的形成。
• Unsaturated hydroxyalkylquinoline acids as leukotriene antagonists
  申请人：MERCK FROSST CANADA INC.

  公开号：EP0480717B1

  公开（公告）日：1998-04-15
• US5202321A
  申请人：——

  公开号：US5202321A

  公开（公告）日：1993-04-13
• US5270324A
  申请人：——

  公开号：US5270324A

  公开（公告）日：1993-12-14