N-methyl-L-phenylalanyl-L-leucine methyl ester | 66444-36-8

• 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: N-methyl-L-phenylalanyl-L-leucine methyl ester
• 英文别名: H-MePhe-Leu-OMe；methyl (2S)-4-methyl-2-[[(2S)-2-(methylamino)-3-phenylpropanoyl]amino]pentanoate
• CAS: 66444-36-8
• 化学式: C₁₇H₂₆N₂O₃
• 分子量: 306.405
• InChiKey: KFHOFFLJCSKNIS-GJZGRUSLSA-N

物化性质

• 沸点：
  456.0±40.0 °C(Predicted)
• 密度：
  1.055±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-methyl-L-phenylalanyl-L-leucine methyl ester 在 sodium hydroxide 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 为溶剂， 反应 4.0h， 生成 N-(benzyloxycarbonyl)-L-tyrosyl-D-threonylglycyl-N-methyl-L-phenylalanyl-L-leucyl-L-threonine benzyl ester
  参考文献：
  名称：

  Investigation of the structural parameters involved in the .mu. and .delta. opioid receptor discrimination of linear enkephalin-related peptides

  摘要：

  The previous rules proposed for selective recognition of mu and delta opioid receptors by modified enkephalins were investigated through an extensive structure-activity study. Thus, modifications of the sequence of TRIMU 4 (Tyr-D-Ala-Gly-NHCH(CH3)CH2CH(CH3)2, a peptide that exhibits mu selectivity close to that of DAGO (Try-D-Ala-Gly-N(Me)Phe-Gly.ol), were performed for two positions, 2 and 4, critical for mu recognition. The drastic loss of potency following introduction of L-Ala or Aib in position 2 emphasizes the importance of the stereochemistry and the steric size of the X2 amino acid for optimal mu binding. The enhancement of the intrinsic flexibility of the C-terminal alkyl chain of TRIMU 4 through removal of a methyl group leads to TRIMU 5 (Tyr-D-Ala-Gly-NHCH2CH2CH(CH3)2), a peptide with a mu selectivity similar to that of DAGO. In contrast, introduction of an O-tert-butyl Ser2 residue increases affinity for delta receptors. In the hexapeptide series derived from DSLET (Tyr-D-Ser-Gly-Phe-Leu-Thr), a D-Thr2 moiety was shown to be very efficient in improving delta recognition and delta selectivity appeared also to be modulated by the nature of the sixth residue. The potencies of the 24 peptides studied to inhibit the electrically evoked contractions of the GPI or MVD are relatively well correlated with their affinities for brain mu or delta receptors labeled with [3H]DAGO or [3H]DSLET, respectively. Moreover, the analgesic potency (hot plate test) of the peptides is related to their affinity for rat brain mu receptors. The wide range of receptor affinities exhibited by the compounds reported here could be useful to study the physiological role of mu and delta receptors.

  DOI：

  10.1021/jm00397a019
• 作为产物：
  描述：

  methyl L-phenylalanyl-L-leucinate hydrochloride 在 三乙基硅烷 、 三氟乙酸 作用下， 以 氯仿 、 水 为溶剂， 反应 22.0h， 生成 N-methyl-L-phenylalanyl-L-leucine methyl ester
  参考文献：
  名称：

  Immonium ion based synthetic methodology: a novel method for the N-methylation of dipeptides and amino acid derivatives via retro aza Diels-Alder reactions

  摘要：

  DOI：

  10.1021/jo00235a021

文献信息

• Organic compounds
  申请人：Sandoz Ltd.

  公开号：US04247543A1

  公开（公告）日：1981-01-27

  The invention provides polypeptides of the formula, A-B-Gly-D-E-F wherein A is Tyr or substituted Tyr, B is, for example, -Gly-, -(D)-Ala-, or -(D)-Met-, D is Phe or substituted Phe, E is, for example, -Leu-, -Nle-, -Nva-, -Ile- or -Val-, and F is -NR.sub.7 CHR.sub.8 CH.sub.2 OR.sub.3 ', wherein, for example, R.sub.3 ' may be hydrogen or alkyl--CO--, R.sub.7 is hydrogen or alkyl and R.sub.8 is alkyl, which compounds possess pharmacological activity, for example, analgesic activity.

  本发明提供了多肽的公式A-B-Gly-D-E-F，其中A是酪氨酸或取代酪氨酸，B是例如-Gly-，-(D)-Ala-或-(D)-Met-，D是苯丙氨酸或取代苯丙氨酸，E是例如-Leu-，-Nle-，-Nva-，-Ile-或-Val-，F是-NR.sub.7 CHR.sub.8 CH.sub.2 OR.sub.3 '，其中，例如，R.sub.3'可以是氢或烷基--CO--，R.sub.7是氢或烷基，R.sub.8是烷基，这些化合物具有药理活性，例如镇痛活性。
• GRIECO, PAUL A.;BAHSAS, ALI, J. ORG. CHEM., 52,(1987) N 26, 5746-5749
  作者：GRIECO, PAUL A.、BAHSAS, ALI

  DOI：——

  日期：——
• Investigation of the structural parameters involved in the .mu. and .delta. opioid receptor discrimination of linear enkephalin-related peptides
  作者：G. Gacel、J. M. Zajac、P. Delay-Goyet、V. Dauge、B. P. Roques

  DOI：10.1021/jm00397a019

  日期：1988.2

  The previous rules proposed for selective recognition of mu and delta opioid receptors by modified enkephalins were investigated through an extensive structure-activity study. Thus, modifications of the sequence of TRIMU 4 (Tyr-D-Ala-Gly-NHCH(CH3)CH2CH(CH3)2, a peptide that exhibits mu selectivity close to that of DAGO (Try-D-Ala-Gly-N(Me)Phe-Gly.ol), were performed for two positions, 2 and 4, critical for mu recognition. The drastic loss of potency following introduction of L-Ala or Aib in position 2 emphasizes the importance of the stereochemistry and the steric size of the X2 amino acid for optimal mu binding. The enhancement of the intrinsic flexibility of the C-terminal alkyl chain of TRIMU 4 through removal of a methyl group leads to TRIMU 5 (Tyr-D-Ala-Gly-NHCH2CH2CH(CH3)2), a peptide with a mu selectivity similar to that of DAGO. In contrast, introduction of an O-tert-butyl Ser2 residue increases affinity for delta receptors. In the hexapeptide series derived from DSLET (Tyr-D-Ser-Gly-Phe-Leu-Thr), a D-Thr2 moiety was shown to be very efficient in improving delta recognition and delta selectivity appeared also to be modulated by the nature of the sixth residue. The potencies of the 24 peptides studied to inhibit the electrically evoked contractions of the GPI or MVD are relatively well correlated with their affinities for brain mu or delta receptors labeled with [3H]DAGO or [3H]DSLET, respectively. Moreover, the analgesic potency (hot plate test) of the peptides is related to their affinity for rat brain mu receptors. The wide range of receptor affinities exhibited by the compounds reported here could be useful to study the physiological role of mu and delta receptors.
• Immonium ion based synthetic methodology: a novel method for the N-methylation of dipeptides and amino acid derivatives via retro aza Diels-Alder reactions
  作者：Paul A. Grieco、Ali Bahsas

  DOI：10.1021/jo00235a021

  日期：1987.12