Cbz-Ile-Glu(OtBu)-Ala-OH | 890660-21-6

• 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: Cbz-Ile-Glu(OtBu)-Ala-OH
• 英文别名: 4-(2-benzyloxycarbonylamino-3-methylpentanoylamino)-4-(1-carboxyethylcarbamoyl)butyric acid tert-butyl ester
• CAS: 890660-21-6
• 化学式: C₂₆H₃₉N₃O₈
• 分子量: 521.611
• InChiKey: ATDSDJQZVCPKTF-VKRLORBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.52
• 重原子数：
  37.0
• 可旋转键数：
  13.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  160.13
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  Cbz-Ile-Glu(OtBu)-Ala-OH 、 2-amino-1-(5-phenyl-[1,3,4]oxadiazol-2-yl)-pentan-1-ol hydrochloride 在 N-甲基吗啉 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 1.17h， 以33%的产率得到4-(2-benzyloxycarbonylamino-3-methylpentanoylamino)-4-(1-{1-[hydroxy-(5-phenyl-[1,3,4]oxadiazol-2-yl)methyl]butylcarbamoyl}ethylcarbamoyl)butyric acid tert-butyl ester
  参考文献：
  名称：

  [EN] PROTEASOME INHIBITORS : PEPTIDE DERIVATIVES HAVING C-TERMINAL HETEROARYL GROUPS
  [FR] INHIBITEURS DU PROTEASOME : DERIVES PEPTIDIQUES COMPRENANT DES GROUPES HETEROARYLE C-TERMINAUX

  摘要：

  公开号：

  WO2004014882A3
• 作为产物：
  描述：

  L-谷氨酸-5-叔丁基酯 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 42.5h， 生成 Cbz-Ile-Glu(OtBu)-Ala-OH
  参考文献：
  名称：

  Optimization of Subsite Binding to the β5 Subunit of the Human 20S Proteasome Using Vinyl Sulfones and 2-Keto-1,3,4-oxadiazoles:  Syntheses and Cellular Properties of Potent, Selective Proteasome Inhibitors

  摘要：

  Beginning with the peptide sequence Cbz-Ile-Glu(OtBu)-Ala-Leu found in PSI (3), a series of vinyl sulfones (VS) were synthesized for evaluation as inhibitors of the chymotrypsin-like activity of the 20S proteasome. Variations at the key P3 position confirmed the importance of a long side chain capped with a hydrophobic group for optimal potency, consistent with a model of binding to the S3 subsite. The tert-butyl glutamic ester initially used at P3 gave plasma unstable, insoluble compounds and was replaced with the better isostere, N-beta-neopentyl asparagine. The inhibitors were shortened by replacing the N-terminal Cbz-isoleucine with a p-tosyl group without loss of potency. Small L-amino acids were used at P2, where D-substitution was not tolerated. The resulting optimized P4-P3-P2 sequence was grafted onto a novel proteasome inhibitor warhead, 2-keto-1,3,4-oxadiazoles (KOD), to produce reversible, subnanomolar proteasome inhibitors that were 1000-fold selective versus cathepsin B (CatB), cathepsin S (CatS), and trypsin-like as well as PGPH-like proteasome activity. A number of compounds in both the VS and the KOD series exhibited growth inhibitory effects against the human prostate cancer cell line PC3 at submicromolar concentrations.

  DOI：

  10.1021/jm058289o