2-[[(2S)-2-[[2-(4-hydroxyphenyl)acetyl]amino]hexanoyl]amino]acetic acid | 199541-48-5

• 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: 2-[[(2S)-2-[[2-(4-hydroxyphenyl)acetyl]amino]hexanoyl]amino]acetic acid
• CAS: 199541-48-5
• 化学式: C₁₆H₂₂N₂O₅
• 分子量: 322.361
• InChiKey: YYLPNDVHEUJXAN-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[[(2S)-2-[[2-(4-hydroxyphenyl)acetyl]amino]hexanoyl]amino]acetic acid 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 为溶剂， 反应 6.08h， 生成 Hpa-Nle-Gly-Trp-Nle-MeAsp-Phe-NH2
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Potent, Selective, Hexapeptide CCK-A Agonist Anorectic Agents

  摘要：

  Cholecystokinin (CCK) is a 33-amino acid peptide with multiple functions in both the central nervous system (via CCK-B receptors) and the periphery (via CCK-A receptors). CCK mediation of satiety via the A-receptor subtype suggest a role for CCK in the management of obesity. The carboxy terminal octapeptide (CCK-8) is fully active in this regard, but is lacking in receptor selectivity, metabolic stability, and oral bioavailability. Inversion of the chirality of Asp(7) in conjunction with N-methylation of Phe(8) produces compound 5 which exhibits high affinity and 2100-fold selectivity for CCK-A receptors. Compound 6 (Hpa(SO3H)-Me-Gly-Trp-Nle-MeAsp-Phe-NH2), derived from moving the N-methyl group from Phe to Asp, decreased CCK-B affinity substantially without affecting CCK-A affinity, giving a compound with 6600-fold selectivity for CCK-A receptors. These compounds inhibit food intake with nanomolar potency following intraperitoneal administration in fasted rats. In addition to greater potency, compound 6 produces weight loss in rats when administered over nine consecutive days. Intranasal administration of 6 potently inhibits feeding in beagle dogs. Compound 6 produces potent anorectic activity via the CCK-A receptor system.

  DOI：

  10.1021/jm970477u
• 作为产物：
  描述：

  N-Boc-L-正亮氨酸 在 盐酸 、 sodium hydroxide 、 三甲基乙酰氯 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.25h， 生成 2-[[(2S)-2-[[2-(4-hydroxyphenyl)acetyl]amino]hexanoyl]amino]acetic acid
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Potent, Selective, Hexapeptide CCK-A Agonist Anorectic Agents

  摘要：

  Cholecystokinin (CCK) is a 33-amino acid peptide with multiple functions in both the central nervous system (via CCK-B receptors) and the periphery (via CCK-A receptors). CCK mediation of satiety via the A-receptor subtype suggest a role for CCK in the management of obesity. The carboxy terminal octapeptide (CCK-8) is fully active in this regard, but is lacking in receptor selectivity, metabolic stability, and oral bioavailability. Inversion of the chirality of Asp(7) in conjunction with N-methylation of Phe(8) produces compound 5 which exhibits high affinity and 2100-fold selectivity for CCK-A receptors. Compound 6 (Hpa(SO3H)-Me-Gly-Trp-Nle-MeAsp-Phe-NH2), derived from moving the N-methyl group from Phe to Asp, decreased CCK-B affinity substantially without affecting CCK-A affinity, giving a compound with 6600-fold selectivity for CCK-A receptors. These compounds inhibit food intake with nanomolar potency following intraperitoneal administration in fasted rats. In addition to greater potency, compound 6 produces weight loss in rats when administered over nine consecutive days. Intranasal administration of 6 potently inhibits feeding in beagle dogs. Compound 6 produces potent anorectic activity via the CCK-A receptor system.

  DOI：

  10.1021/jm970477u