TY042 | 1181341-90-1

• 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: TY042
• 英文别名: H-Tyr-D-Ala-Gly-Phe-Ser(Glc)-Pro-Leu-Trp-NH-3,5-Bzl(CF3)2；(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypropanoyl]-N-[(2S)-1-[[(2S)-1-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pyrrolidine-2-carboxamide
• CAS: 1181341-90-1
• 化学式: C₆₃H₇₆F₆N₁₀O₁₅
• 分子量: 1327.34
• InChiKey: WMTKHCQGJKXVST-PYIJLGDTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  94
• 可旋转键数：
  28
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  385
• 氢给体数：
  14
• 氢受体数：
  22

反应信息

• 作为产物：
  描述：

  Fmoc-甘氨酸 、 Fmoc-L-亮氨酸 、 Fmoc-L-脯氨酸 、 Fmoc-L-苯丙氨酸 、 Fmoc-O-叔丁基-L-酪氨酸 、 Fmoc-D-丙氨酸 、 葡萄糖丝氨酸 、 3,5-双(三氟甲基)苄胺 、 Fmoc-L-色氨酸(Boc)-OH 在 盐酸 、 原甲酸三甲酯 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 TY042
  参考文献：
  名称：

  Improving Metabolic Stability by Glycosylation: Bifunctional Peptide Derivatives That Are Opioid Receptor Agonists and Neurokinin 1 Receptor Antagonists

  摘要：

  In order to obtain a metabolically more stable analgesic peptide derivative, O-beta-glycosylated serine (Ser(Glc)) was introduced into TY027 (Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-3',5'-Bzl(CF3)(2)) which was a previously reported bifunctional compound with delta/mu opioid agonist and neurokinin-1 receptor antagonist activities and with a half-life of 4.8 h in rat plasma. Incorporation of Ser(Glc) into various positions of TY027 gave analogues with variable bioactivities. Analogue 6 (Tyr-D-Ala-Gly-Phe-Nle-Pro-Leu-Ser(Glc)-Trp-NH-3',5'-Bzl(CF3)(2)) was found to have effective bifunctional activities with a well-defined conformation with two beta-turns based on the NMR conformational analysis in the presence of DPC micelles. In addition, 6 showed significant improvement In its metabolic stability (70 +/- 9% of 6 was intact after 24 h incubation in rat plasma). This improved metabolic stability, along, with its effective and delta selective bifunctional activities, suggests that 6 Could be all interesting research tool and possibly a promising candidate as a novel analgesic drug.

  DOI：

  10.1021/jm900473p