(2S)-3-methyl-2-(((phenylamino)thioxomethyl)amino)-N-((3S)-tetrahydro-2-oxo-3-furanyl)butanamide | 900802-88-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)-3-methyl-2-(((phenylamino)thioxomethyl)amino)-N-((3S)-tetrahydro-2-oxo-3-furanyl)butanamide
• 英文别名: (2S)-3-methyl-N-[(3S)-2-oxooxolan-3-yl]-2-(phenylcarbamothioylamino)butanamide
• CAS: 900802-88-2
• 化学式: C₁₆H₂₁N₃O₃S
• 分子量: 335.427
• InChiKey: FLRXODOASASQHL-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S)-3-methyl-2-(((phenylamino)thioxomethyl)amino)-N-((3S)-tetrahydro-2-oxo-3-furanyl)butanamide 在 二异丁基氢化铝 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 3.0h， 以1.3 g的产率得到(2S)-3-methyl-2-(((phenylamino)thioxomethyl)amino)-N-((3S)-tetrahydro-2-hydroxy-3-furanyl)butanamide
  参考文献：
  名称：

  Exploration of Orally Available Calpain Inhibitors 2:  Peptidyl Hemiacetal Derivatives

  摘要：

  We previously reported a potent calpain inhibitor 1 ( SJA6017, N-( 4-fluorophenyl)-L-valyl-L-leucinal), which displayed relatively low oral bioavailability ( BA). Replacing the metabolically labile aldehyde moiety of 1 with more chemically stable warheads, such as a cyclic hemiacetal, hydrazone, and alpha-ketoamide, provided the inhibitors with improved in vitro metabolic stability. Cyclic hemiacetal 2 was the most stable of these compounds. The optimization of 2 led to hemiacetal 8 ( SNJ-1715) which exhibited high potency, good aqueous solubility, excellent oral BA, and prolonged plasma half-life in rats. Furthermore, 8 showed neuroprotective efficacy via oral administration in a rat retinal ischemia model.

  DOI：

  10.1021/jm060157n
• 作为产物：
  描述：

  Boc-L-缬氨酸羟基琥珀酰亚胺酯 在 盐酸 、 三乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 (2S)-3-methyl-2-(((phenylamino)thioxomethyl)amino)-N-((3S)-tetrahydro-2-oxo-3-furanyl)butanamide
  参考文献：
  名称：

  Exploration of Orally Available Calpain Inhibitors 2:  Peptidyl Hemiacetal Derivatives

  摘要：

  We previously reported a potent calpain inhibitor 1 ( SJA6017, N-( 4-fluorophenyl)-L-valyl-L-leucinal), which displayed relatively low oral bioavailability ( BA). Replacing the metabolically labile aldehyde moiety of 1 with more chemically stable warheads, such as a cyclic hemiacetal, hydrazone, and alpha-ketoamide, provided the inhibitors with improved in vitro metabolic stability. Cyclic hemiacetal 2 was the most stable of these compounds. The optimization of 2 led to hemiacetal 8 ( SNJ-1715) which exhibited high potency, good aqueous solubility, excellent oral BA, and prolonged plasma half-life in rats. Furthermore, 8 showed neuroprotective efficacy via oral administration in a rat retinal ischemia model.

  DOI：

  10.1021/jm060157n

文献信息

• Cyclic hemiacetal derivative and use thereof
  申请人：Nakamura Masayuki

  公开号：US20050119499A1

  公开（公告）日：2005-06-02

  A compound represented by the following formula (I) wherein R 1 is a lower alkyl group, R 2 is a hydrogen, a halogen, a cyano group, a lower alkyl group or a lower alkoxy group, and n is 0 or 1, which has a calpain inhibitory activity, is provided.

  下式(I)代表的化合物 其中 R 1 是低级烷基，R 2 是氢、卤素、氰基、低级烷基或低级烷氧基，n 是 0 或 1，该化合物具有钙蛋白酶抑制活性。
• CYCLIC HEMIACETAL DERIVATIVE AND USE THEREOF
  申请人：Senju Pharmaceutical Co., Ltd.

  公开号：EP1489076B1

  公开（公告）日：2008-08-13
• US7202274B2
  申请人：——

  公开号：US7202274B2

  公开（公告）日：2007-04-10