H-Tyr-D-Arg-Gly-4-nitro-L-phenylalanyl-Pro-NH2 diacetate | 88331-14-0

• 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: H-Tyr-D-Arg-Gly-4-nitro-L-phenylalanyl-Pro-NH2 diacetate
• 英文别名: L-tyrosyl-D-arginylglycyl-L-4-nitrophenylalanyl-L-prolinamide diacetate；BW443C；H-Tyr-D-Arg-Gly-Phe(4-NO2)-Pro-NH2.CH3CO2H；acetic acid;(2S)-1-[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-3-(4-nitrophenyl)propanoyl]pyrrolidine-2-carboxamide
• CAS: 88331-14-0
• 化学式: 2C₂H₄O₂*C₃₁H₄₂N₁₀O₈
• 分子量: 802.842
• InChiKey: KUFWHEYTKALCIE-DKVOZMMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.88
• 重原子数：
  53
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  345
• 氢给体数：
  9
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  1-amidino-3,5-dimethylpyrazole acetate 、 H-Tyr-D-Arg-Gly-4-nitro-L-phenylalanyl-Pro-NH2 diacetate 在 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 以42%的产率得到N1-amidino-L-tyrosyl-D-arginylglycyl-L-4-nitrophenylalanyl-L-prolinamide diacetate
  参考文献：
  名称：

  Peripherally acting enkephalin analogs. 1. Polar pentapeptides

  摘要：

  The design, synthesis, and biological activity of a series of highly polar enkephalin-related pentapeptides are reported. These analogues incorporate structural features that exclude them from the central nervous system and thereby restrict their action to peripherally located receptors. Hydrophilic analogues were obtained by introduction of polar D-amino acid residues at position 2 and, in certain cases, by conversion of the N-terminal amino group of the Tyr residue to a guanidino function. The peptides were synthesized by classical solution methods. All compounds demonstrated in vitro opioid activity in the GPI and all were shown to possess antinociceptive activity in chemically induced writhing models. The analgesic effects were shown to be predominantly peripherally mediated by antagonism of antinociception with the peripheral antagonist N-methylnalorphine. Comparative data obtained in writhing and hot-plate tests were also supportive of a peripheral mode of action. Compound 13a, L-tyrosyl-D-arginylglycyl-L-4-nitrophenylalanyl-L-prolinamide (BW 443C), was identified as having a favorable pharmacological profile, indicating a high level of peripheral selectivity, and worthy of further investigation.

  DOI：

  10.1021/jm00400a012
• 作为产物：
  描述：

  N-(tert-butyloxycarbonyl)-L-tyrosyl-D-arginine hydrochloride 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 、 苯甲醚 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 为溶剂， 反应 73.25h， 生成 H-Tyr-D-Arg-Gly-4-nitro-L-phenylalanyl-Pro-NH2 diacetate
  参考文献：
  名称：

  Peripherally acting enkephalin analogs. 1. Polar pentapeptides

  摘要：

  The design, synthesis, and biological activity of a series of highly polar enkephalin-related pentapeptides are reported. These analogues incorporate structural features that exclude them from the central nervous system and thereby restrict their action to peripherally located receptors. Hydrophilic analogues were obtained by introduction of polar D-amino acid residues at position 2 and, in certain cases, by conversion of the N-terminal amino group of the Tyr residue to a guanidino function. The peptides were synthesized by classical solution methods. All compounds demonstrated in vitro opioid activity in the GPI and all were shown to possess antinociceptive activity in chemically induced writhing models. The analgesic effects were shown to be predominantly peripherally mediated by antagonism of antinociception with the peripheral antagonist N-methylnalorphine. Comparative data obtained in writhing and hot-plate tests were also supportive of a peripheral mode of action. Compound 13a, L-tyrosyl-D-arginylglycyl-L-4-nitrophenylalanyl-L-prolinamide (BW 443C), was identified as having a favorable pharmacological profile, indicating a high level of peripheral selectivity, and worthy of further investigation.

  DOI：

  10.1021/jm00400a012

文献信息

• Peripherally acting enkephalin analogs. 1. Polar pentapeptides
  作者：George W. Hardy、Lawrence A. Lowe、Pang Yih Sang、Dean S. A. Simpkin、Samuel Wilkinson、Rhonda L. Follenfant、Terence W. Smith

  DOI：10.1021/jm00400a012

  日期：1988.5

  The design, synthesis, and biological activity of a series of highly polar enkephalin-related pentapeptides are reported. These analogues incorporate structural features that exclude them from the central nervous system and thereby restrict their action to peripherally located receptors. Hydrophilic analogues were obtained by introduction of polar D-amino acid residues at position 2 and, in certain cases, by conversion of the N-terminal amino group of the Tyr residue to a guanidino function. The peptides were synthesized by classical solution methods. All compounds demonstrated in vitro opioid activity in the GPI and all were shown to possess antinociceptive activity in chemically induced writhing models. The analgesic effects were shown to be predominantly peripherally mediated by antagonism of antinociception with the peripheral antagonist N-methylnalorphine. Comparative data obtained in writhing and hot-plate tests were also supportive of a peripheral mode of action. Compound 13a, L-tyrosyl-D-arginylglycyl-L-4-nitrophenylalanyl-L-prolinamide (BW 443C), was identified as having a favorable pharmacological profile, indicating a high level of peripheral selectivity, and worthy of further investigation.