Z-Phe-D-Trp-D-Trp-OMe | 140834-94-2

• 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: Z-Phe-D-Trp-D-Trp-OMe
• 英文别名: methyl (2R)-3-(1H-indol-3-yl)-2-[[(2R)-3-(1H-indol-3-yl)-2-[[(2S)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoyl]amino]propanoyl]amino]propanoate
• CAS: 140834-94-2
• 化学式: C₄₀H₃₉N₅O₆
• 分子量: 685.78
• InChiKey: GQMXGYRHPPPVFO-LIVOIKKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.11
• 重原子数：
  51.0
• 可旋转键数：
  14.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  154.41
• 氢给体数：
  5.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  Z-Phe-D-Trp-D-Trp-OMe 在 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以89.1%的产率得到Z-Phe-D-Trp-D-Trp-OH
  参考文献：
  名称：

  Studies on neurokinin antagonists. 1. The design of novel tripeptides possessing glutaminyl-D-tryptophylphenylalanine sequence as substance P antagonists

  摘要：

  To discover a novel and low molecular weight substance P (SP) antagonist we postulated that the essential binding domain of peptide ligands was only a small portion in the whole structure. On the basis of this assumption, we selected the known octapeptide SP antagonist D-Pro-Gln-Gln-D-Trp-Phe-D-Trp-D-Trp-Phe-NH2 (1) as a lead and synthesized its fragment tripeptides which were evaluated for their activity to block H-3-SP binding on guinea pig lung membranes. The protected tripeptide N(alpha)-[N(alpha)-[N(alpha)-(tert-butyloxycarbonyl)-L-glutaminyl]-N1-formyl-D-tryptophyl]-L-phenylalanine benzyl ester [Boc-Gln-D-Trp(CHO)-Phe-OBzl (4a)], corresponding to the Gln-D-Trp-Phe part of 1, exhibited 7-fold potent inhibitory activity in comparison with 1. Studies on structure-activity relationships revealed that the D-tryptophan, L-phenylalanine, and benzyl ester were quite important to maintain the high binding affinity. It was also indicated that 4a antagonized the SP-induced contraction of isolated guinea pig trachea strips (IC50 = 4.7 x 10(-6) M).

  DOI：

  10.1021/jm00089a011
• 作为产物：
  描述：

  N-苄氧羰基-D-色氨酸 在 palladium on activated charcoal 盐酸 、 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 Z-Phe-D-Trp-D-Trp-OMe
  参考文献：
  名称：

  Studies on neurokinin antagonists. 1. The design of novel tripeptides possessing glutaminyl-D-tryptophylphenylalanine sequence as substance P antagonists

  摘要：

  To discover a novel and low molecular weight substance P (SP) antagonist we postulated that the essential binding domain of peptide ligands was only a small portion in the whole structure. On the basis of this assumption, we selected the known octapeptide SP antagonist D-Pro-Gln-Gln-D-Trp-Phe-D-Trp-D-Trp-Phe-NH2 (1) as a lead and synthesized its fragment tripeptides which were evaluated for their activity to block H-3-SP binding on guinea pig lung membranes. The protected tripeptide N(alpha)-[N(alpha)-[N(alpha)-(tert-butyloxycarbonyl)-L-glutaminyl]-N1-formyl-D-tryptophyl]-L-phenylalanine benzyl ester [Boc-Gln-D-Trp(CHO)-Phe-OBzl (4a)], corresponding to the Gln-D-Trp-Phe part of 1, exhibited 7-fold potent inhibitory activity in comparison with 1. Studies on structure-activity relationships revealed that the D-tryptophan, L-phenylalanine, and benzyl ester were quite important to maintain the high binding affinity. It was also indicated that 4a antagonized the SP-induced contraction of isolated guinea pig trachea strips (IC50 = 4.7 x 10(-6) M).

  DOI：

  10.1021/jm00089a011