{(S)-1-[Hydroxy-(5-isopropyl-[1,3,4]oxadiazol-2-yl)-methyl]-2-methyl-propyl}-carbamic acid tert-butyl ester | 1027934-86-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: {(S)-1-[Hydroxy-(5-isopropyl-[1,3,4]oxadiazol-2-yl)-methyl]-2-methyl-propyl}-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S)-1-hydroxy-3-methyl-1-(5-propan-2-yl-1,3,4-oxadiazol-2-yl)butan-2-yl]carbamate
• CAS: 1027934-86-6
• 化学式: C₁₅H₂₇N₃O₄
• 分子量: 313.397
• InChiKey: MLHYFKFUCRXSAR-VUWPPUDQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  97.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  {(S)-1-[Hydroxy-(5-isopropyl-[1,3,4]oxadiazol-2-yl)-methyl]-2-methyl-propyl}-carbamic acid tert-butyl ester 在 N-甲基吗啉 、 盐酸 、 三氯化铝 、 草酰氯 、 1-羟基苯并三唑 、 二甲基亚砜 、 苯甲醚 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 硝基甲烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 2-[5-amino-6-oxo-2-(4-fluorophenyl)-1,6-dihydro-1-pyrimidinyl]-N-[(1S)-1-[[5-(1-methylethyl)-1,3,4-oxadiazole-2-yl]carbonyl]-2-methylpropyl]acetamide
  参考文献：
  名称：

  Development of Orally Active Nonpeptidic Inhibitors of Human Neutrophil Elastase

  摘要：

  5-Amino-2-phenylpyrimidin-6-ones, some of their desamino derivatives, and miscellaneous derivatives were synthesized and biologically evaluated on both in vitro activity and oral activity in an acute hemorrhagic assay. These compounds contained an alpha -keto-1,3,4-oxadiazole moiety to bind covalently to the Ser-195 hydroxy group of human neutrophil elastase (HNE). Among those tested, compounds 11a-c,e,i-1(F), 11d,e,k(H), ald,e,k(F), and ald,e(H) showed a good oral profile. RS-Mixture 3(H) was selected for clinical evaluation based on its oral potency, duration of action, enzyme selectivity, safety profile, and ease of synthesis. Structure-activity relationships (SARs) are discussed.

  DOI：

  10.1021/jm000410y
• 作为产物：
  描述：

  N-BOC-2(S)-2-AMINO-3-METHYL-BUTAL聽 、 2-异丙基-1,3,4-噁二唑 在 正丁基锂 、 magnesium bromide 作用下， 以 正己烷 、 四氢呋喃 为溶剂， 反应 1.5h， 生成 {(S)-1-[Hydroxy-(5-isopropyl-[1,3,4]oxadiazol-2-yl)-methyl]-2-methyl-propyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Development of Orally Active Nonpeptidic Inhibitors of Human Neutrophil Elastase

  摘要：

  5-Amino-2-phenylpyrimidin-6-ones, some of their desamino derivatives, and miscellaneous derivatives were synthesized and biologically evaluated on both in vitro activity and oral activity in an acute hemorrhagic assay. These compounds contained an alpha -keto-1,3,4-oxadiazole moiety to bind covalently to the Ser-195 hydroxy group of human neutrophil elastase (HNE). Among those tested, compounds 11a-c,e,i-1(F), 11d,e,k(H), ald,e,k(F), and ald,e(H) showed a good oral profile. RS-Mixture 3(H) was selected for clinical evaluation based on its oral potency, duration of action, enzyme selectivity, safety profile, and ease of synthesis. Structure-activity relationships (SARs) are discussed.

  DOI：

  10.1021/jm000410y