Boc-Phe-MeβAla-OBzl | 188687-69-6

• 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-Phe-MeβAla-OBzl
• 英文别名: benzyl 3-[methyl-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]propanoate
• CAS: 188687-69-6
• 化学式: C₂₅H₃₂N₂O₅
• 分子量: 440.539
• InChiKey: CUTGLZDNLUHVDA-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Boc-Phe-MeβAla-OBzl 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.42h， 生成 H-Tyr(Bzl)-D-Arg(Cbz2)-Phe-MeβAla-OBzl
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of an Orally Available and Long-Acting Analgesic Peptide, N^α-Amidino-Tyr-d-Arg-Phe-MeβAla-OH (ADAMB)

  摘要：

  A novel dermorphin tetrapeptide N-alpha-amidino-Tyr-D-Arg-Phe-MebetaAla-OH (ADAMB) was designed based on the structures of several dermorphin tetrapeptide analogues, including N-alpha-amidino-Tyr-D-Arg-Phe-Gly-OH (ADA-DER), H-Tyr-D-Arg-Phe-betaAla-OH (TAPA), and H-Tyr-D-Arg-Phe-Sar-OH (DAS-DER). These parent compounds were known to show a weak oral analgesic activity in animals and/or to possess a different mechanism of analgesia from othery mu-opioid peptides. Six analogues of ADAMB were also synthesized to investigate the effect on potency of N-terminal amidination and N-methyl-beta-alanine (MebetaAla) substitution at position 4. Compounds were assessed using the tail pressure test in mice after subcutaneous and oral administration. Among the peptides tested, ADAMB showed the strongest oral antinociceptive activity, with an ED50 of 5.8 vs 22.2 mg/kg for morphine, as well as a 38-fold stronger activity after subcutaneous administration. ADAMB also showed long-lasting antinociceptive activity, with 50% of the maximum effect persisting in the tail pressure test at 10 h after oral administration (10 mg/kg). In contrast, orally administered morphine (80 mg/kg) showed a rapid decrease of activity in the same. test and its antinociceptive effect disappeared within 4 h. When the antinociceptive effect of ADAMB was compared with that of analogues possessing betaAla(4) (1) or Sar(4) (2), as well as analogues with N-substitution (3-6), it was found that both the N-alpha-amidino substitution and the MebetaAla(4) were synergistically involved in creating ADAMB's exceptionally high antinociceptive activity.

  DOI：

  10.1021/jm010357t
• 作为产物：
  描述：

  BOC-L-苯丙氨酸 、 benzyl N-methyl-4-aminobutanoate p-toluenesulfonate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙酸乙酯 为溶剂， 以95.9%的产率得到Boc-Phe-MeβAla-OBzl
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of an Orally Available and Long-Acting Analgesic Peptide, N^α-Amidino-Tyr-d-Arg-Phe-MeβAla-OH (ADAMB)

  摘要：

  A novel dermorphin tetrapeptide N-alpha-amidino-Tyr-D-Arg-Phe-MebetaAla-OH (ADAMB) was designed based on the structures of several dermorphin tetrapeptide analogues, including N-alpha-amidino-Tyr-D-Arg-Phe-Gly-OH (ADA-DER), H-Tyr-D-Arg-Phe-betaAla-OH (TAPA), and H-Tyr-D-Arg-Phe-Sar-OH (DAS-DER). These parent compounds were known to show a weak oral analgesic activity in animals and/or to possess a different mechanism of analgesia from othery mu-opioid peptides. Six analogues of ADAMB were also synthesized to investigate the effect on potency of N-terminal amidination and N-methyl-beta-alanine (MebetaAla) substitution at position 4. Compounds were assessed using the tail pressure test in mice after subcutaneous and oral administration. Among the peptides tested, ADAMB showed the strongest oral antinociceptive activity, with an ED50 of 5.8 vs 22.2 mg/kg for morphine, as well as a 38-fold stronger activity after subcutaneous administration. ADAMB also showed long-lasting antinociceptive activity, with 50% of the maximum effect persisting in the tail pressure test at 10 h after oral administration (10 mg/kg). In contrast, orally administered morphine (80 mg/kg) showed a rapid decrease of activity in the same. test and its antinociceptive effect disappeared within 4 h. When the antinociceptive effect of ADAMB was compared with that of analogues possessing betaAla(4) (1) or Sar(4) (2), as well as analogues with N-substitution (3-6), it was found that both the N-alpha-amidino substitution and the MebetaAla(4) were synergistically involved in creating ADAMB's exceptionally high antinociceptive activity.

  DOI：

  10.1021/jm010357t