isoleucylhomoserine lactone hydrochloride | 704867-65-2

• 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: isoleucylhomoserine lactone hydrochloride
• 英文别名: (2S,3S)-2-amino-3-methyl-N-[(3S)-2-oxooxolan-3-yl]pentanamide
• CAS: 704867-65-2
• 化学式: C₁₀H₁₈N₂O₃
• 分子量: 214.265
• InChiKey: NQNZALWRYNEODB-FXQIFTODSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.21
• 重原子数：
  15.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  81.42
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  isoleucylhomoserine lactone hydrochloride 在 二异丁基氢化铝 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 、 甲苯 为溶剂， 反应 6.0h， 生成 (2S,3S)-3-Methyl-2-(3-phenyl-thioureido)-pentanoic acid ((S)-2-hydroxy-tetrahydro-furan-3-yl)-amide
  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：

  (2S)-2-((tert-butoxy)carbonylamino)-3-methyl-N-((3S)-tetrahydro-2-oxo-3-furanyl)pentanamide 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 18.0h， 生成 isoleucylhomoserine lactone hydrochloride
  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

• Pseudopeptide Inhibitors of Ras Farnesyl-Protein Transferase
  作者：Samuel L. Graham、S. Jane deSolms、Elizabeth A. Giuliani、Nancy E. Kohl、Scott D. Mosser、Allen I. Oliff、David L. Pompliano、Elaine Rands、Michael J. Breslin

  DOI：10.1021/jm00032a004

  日期：1994.3

  Inhibitors of Ras farnesyl-protein transferase are described. These are reduced pseudopeptides related to the C-terminal tetrapeptide of the Ras protein that signals farnesylation. Deletion of the carbonyl groups between the first two residues of the tetrapeptides either preserves or improves activity, depending on the peptide sequence. The most potent in vitro enzyme inhibitor described (IC50 = 5 nM) is Cys[PSICH2NH]Ile[PSICH2NH]Phe-Met(3). To obtain compounds able to suppress Ras farnesylation in cell culture, further structural modification to include a homoserine lactone prodrug was required. Compound 18(Cys[PSICH2NH]Ile[PSICH2NH]Ile-homoserine lactone)reduced the extent of Ras farnesylation by 50 % in NIH3T3 fibroblasts in culture at a concentration of 50 muM. Structure-activity studies also led to 12 (Cys[PSICH2NH]Val-Ile-Leu), a potent and selective inhibitor of a related enzyme, the type-I geranylgeranyl protein transferase.