L-高苯丙氨酸叔丁酯盐酸盐 | 130316-46-0

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 苯丙氨酸类衍生物
• 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
• 中文名称: L-高苯丙氨酸叔丁酯盐酸盐
• 英文名称: (S)-2-Amino-4-phenyl-butyric acid tert-butyl ester; hydrochloride
• 英文别名: L-Homophenylalanine tert-butyl ester hydrochloride；tert-butyl (2S)-2-amino-4-phenylbutanoate;hydrochloride
• CAS: 130316-46-0
• 化学式: C₁₄H₂₁NO₂*ClH
• 分子量: 271.787
• InChiKey: ZBJGZYBRHPJMEG-YDALLXLXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.71
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  52.3
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2922499990
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  L-高苯丙氨酸叔丁酯盐酸盐 在 palladium on activated charcoal 氢气 、 sodium acetate 、 sodium cyanoborohydride 作用下， 以 甲醇 、 乙醇 为溶剂， 25.0 ℃ 、405.3 kPa 条件下， 反应 20.0h， 生成 N-(1(S)-(tert-Butyloxycarbonyl)-3-phenylpropyl)-L-leucine
  参考文献：
  名称：

  Nonpeptide renin inhibitors employing a novel 3-aza (or oxa)-2,4-dialkyl glutaric acid moiety as a P2/P3 amide bond replacement

  摘要：

  A new series of renin inhibitors has been developed. The inhibitors feature a novel replacement for the P2/P3 dipeptide moiety normally associated with renin inhibitors. The dipeptide replacement was a (2S,4S)-3-aza(or oxa)-2,4-di-alkylglutaric acid amide. Extensive structure-activity relationship studies determined that optimum potency was achieved when inhibitors employed a benzyl and butyl group at the C(4) and C(2) carbon position, respectively. In addition, maximum in vitro potency was obtained when the N-terminus was functionalized by incorporating a 4-(1,3-dioxabutyl)piperidine amide. SAR data suggested that the 1,3-dioxabutyl group (methoxymethyl ether) interacted by hydrogen bonding to groups in the S4 domain of renin. This hypothesis was strengthened when a 4-butylpiperidine amide was substituted and inhibitor potency decreased dramatically. Inhibitors employing this novel dipeptide mimic were prepared by coupling the glutaric acid amides with either the transition-state mimic (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (18) or the hydroxyethylene dipeptide isostere. The glutaric acid amides were prepared by two general procedures. The first procedure involved the reductive amination of alpha-amino acid esters with alpha-keto esters. The second procedure involved the displacement reaction of alpha-bromo esters or acids with alpha-amino acid amides.

  DOI：

  10.1021/jm00088a006

文献信息

• Nonpeptide renin inhibitors employing a novel 3-aza (or oxa)-2,4-dialkyl glutaric acid moiety as a P2/P3 amide bond replacement
  作者：William R. Baker、Anthony K. L. Fung、Hollis D. Kleinert、Herman H. Stein、Jacob J. Plattner、Yoek Lin Armiger、Stephen L. Condon、Jerome Cohen、David A. Egan

  DOI：10.1021/jm00088a006

  日期：1992.5

  A new series of renin inhibitors has been developed. The inhibitors feature a novel replacement for the P2/P3 dipeptide moiety normally associated with renin inhibitors. The dipeptide replacement was a (2S,4S)-3-aza(or oxa)-2,4-di-alkylglutaric acid amide. Extensive structure-activity relationship studies determined that optimum potency was achieved when inhibitors employed a benzyl and butyl group at the C(4) and C(2) carbon position, respectively. In addition, maximum in vitro potency was obtained when the N-terminus was functionalized by incorporating a 4-(1,3-dioxabutyl)piperidine amide. SAR data suggested that the 1,3-dioxabutyl group (methoxymethyl ether) interacted by hydrogen bonding to groups in the S4 domain of renin. This hypothesis was strengthened when a 4-butylpiperidine amide was substituted and inhibitor potency decreased dramatically. Inhibitors employing this novel dipeptide mimic were prepared by coupling the glutaric acid amides with either the transition-state mimic (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (18) or the hydroxyethylene dipeptide isostere. The glutaric acid amides were prepared by two general procedures. The first procedure involved the reductive amination of alpha-amino acid esters with alpha-keto esters. The second procedure involved the displacement reaction of alpha-bromo esters or acids with alpha-amino acid amides.