Boc-Trp-Nle-(N-Me)Asp(OBn)-Phe-NH2 | 141982-67-4

• 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: Boc-Trp-Nle-(N-Me)Asp(OBn)-Phe-NH2
• 英文别名: benzyl (3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-3-(1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]hexanoyl]-methylamino]-4-oxobutanoate
• CAS: 141982-67-4
• 化学式: C₄₃H₅₄N₆O₈
• 分子量: 782.937
• InChiKey: OYOWALZFTGQJAK-ZYADHFCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.45
• 重原子数：
  57.0
• 可旋转键数：
  19.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  202.02
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  Boc-Trp-Nle-(N-Me)Asp(OBn)-Phe-NH2 在 palladium on activated charcoal 吡啶 、 亚磷酸氢二甲酯 、 三氧化硫 、 氢气 、 苯甲醚 、 三乙胺 作用下， 以 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、405.3 kPa 条件下， 反应 121.0h， 生成 (des-NH2)Tyr(SO3^-)-Nle-Gly-Trp-Nle-(N-Me)Asp-Phe
  参考文献：
  名称：

  Synthesis and biological activity of CCK heptapeptide analogs. Effects of conformational constraints and standard modifications on receptor subtype selectivity, functional activity in vitro, and appetite suppression in vivo

  摘要：

  A series of modifications of the CCK7 analogue (des-NH2)Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp-Phe-NH2 was prepared and tested for binding to guinea pig CCK-A and CCK-B receptors and in CCK-A-mediated functional assays. Selected analogues also were tested for appetite suppressant activity in rats. Several conformationally restricted residues in the C-terminal tetrapeptide region, including DELTA(Z)-Phe33, (N-Me)Phe33, (N-Me)Asp32, (N-Me)Leu31, and 3PP31 (3PP = trans-3-n-propyl-L-proline) were found to be acceptable modifications at one or both receptor subtypes. The (N-Me)Asp32 and (N-Me)Leu31 modifications afforded potent and selective CCK-A and CCK-B ligands, respectively. SAR studies in the N-terminal acyldipeptide region examined structural requirements for the side chain at position 28, where Gly and Pro replacements were found to possess high affinity at both receptor subtypes. Other conformationally restrictive modifications were less active. All of the analogues that showed high affinity (<10 nM) for the CCK-A receptor also were full agonists in amylase release and most were full or nearly full agonists in the phosphoinositide (PI) turnover assay, the most notable exception being the DELTA(Z)-Phe33 analogue, which showed 69% of the maximal response in the PI assay. Potent activity in suppression of food intake in rats was found for selected analogues.

  DOI：

  10.1021/jm00094a001
• 作为产物：
  描述：

  L-苯丙氨酰胺盐酸盐 在 盐酸 、 三甲基乙酰氯 、 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 乙酸乙酯 为溶剂， 反应 8.42h， 生成 Boc-Trp-Nle-(N-Me)Asp(OBn)-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