(2S,3S,5S)-2-amino-1-cyclohexyl-3-hydroxy-5-(n-butylcarbamoyl)-6-methylheptane hydrochloride | 132154-76-8

• 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,3S,5S)-2-amino-1-cyclohexyl-3-hydroxy-5-(n-butylcarbamoyl)-6-methylheptane hydrochloride
• 英文别名: [αS-(αR*,γR*,δR*)]δ-Amino-N-butyl-γ-hydroxy-α-(1-methylethyl)-cyclohexanehexanamide hydrochloride
• CAS: 132154-76-8
• 化学式: C₁₉H₃₈N₂O₂*ClH
• 分子量: 362.984
• InChiKey: OSCAGQDAAPBGKK-UVJOBNTFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.65
• 重原子数：
  24.0
• 可旋转键数：
  10.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  75.35
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (2S,3S,5S)-2-amino-1-cyclohexyl-3-hydroxy-5-(n-butylcarbamoyl)-6-methylheptane hydrochloride 、 (2S,4S)-3-aza-2-butyl-4-<<4-(1,3-dioxabutyl)piperidin-1-yl>carbonyl>-5-phenylpentanoic acid 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 (2S,4S)-3-aza-2-butyl-4-<<4-(1,3-dioxabutyl)piperidin-1-yl>carbonyl>-5-phenylpentanamide of (2S,3S,5S)-2-amino-1-cyclohexyl-3-hydroxy-5-(n-butylcarbamoyl)-6-methylheptane
  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
• 作为产物：
  描述：

  5-[2-[(Butylamino)carbonyl]-3-methylbutyl]-4-(cyclohexylmethyl)-2,2-dimethyl-3-oxazolidinecarboxylic acid, 1,1-dimethylethyl ester 以 1,4-二氧六环 、 盐酸 、 甲醇 为溶剂， 以54%的产率得到(2S,3S,5S)-2-amino-1-cyclohexyl-3-hydroxy-5-(n-butylcarbamoyl)-6-methylheptane hydrochloride
  参考文献：
  名称：

  5-amino-6-cyclohexyl-4-hydroxy-hexanamide derivatives as inhibitors of

  摘要：

  已经合成了一系列公式I的5-氨基-6-环己基-4-羟基-己酰胺衍生物。作为β-淀粉样前体蛋白β-淀粉样蛋白的产生抑制剂，这些化合物预计可有效治疗患有或易感患有与β-淀粉样蛋白脑积累相关的疾病或症状，例如阿尔茨海默病和唐氏综合症的患者。

  公开号：

  US05703129A1