N-(tert-butyloxycarbonyl)-L-tyrosyl-D-methionylglycine methyl ester | 70777-31-0

• 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: N-(tert-butyloxycarbonyl)-L-tyrosyl-D-methionylglycine methyl ester
• 英文别名: Boc-Tyr-D-Met-Gly-OMe；methyl 2-[[(2R)-2-[[(2S)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-4-methylsulfanylbutanoyl]amino]acetate
• CAS: 70777-31-0
• 化学式: C₂₂H₃₃N₃O₇S
• 分子量: 483.586
• InChiKey: MMVVMZRPRXFUBF-SJORKVTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  33
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  168
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(tert-butyloxycarbonyl)-L-tyrosyl-D-methionylglycine methyl ester 在 sodium hydroxide 、 水 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 Boc Tyr D.Met Gly Phe Pro OMe
  参考文献：
  名称：

  Audigier; Mazarguil; Gout, European Journal of Medicinal Chemistry, 1980, vol. 15, # 2, p. 173 - 177

  摘要：

  DOI：
• 作为产物：
  描述：

  Boc tyrosine 在 sodium hydroxide 、 水 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 formamide 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(tert-butyloxycarbonyl)-L-tyrosyl-D-methionylglycine methyl ester
  参考文献：
  名称：

  Audigier; Mazarguil; Gout, European Journal of Medicinal Chemistry, 1980, vol. 15, # 2, p. 173 - 177

  摘要：

  DOI：

文献信息

• N-Adamantane-substituted tetrapeptide amides
  申请人：G. D. Searle & Co.

  公开号：US04273704A1

  公开（公告）日：1981-06-16

  N-Adamantane-substituted tetrapeptide amides and the pharmacologically acceptable salts thereof are disclosed herein. These compounds are analogs of enkephalin wherein the methionine or leucine of position 5 has been substituted by an adamantyl amide and the glycine of position 2 has been substituted by various amino acid residues. Optionally the tyrosine of position 1 and the phenylalanine of position 4 may be substituted by various amino acid residues. These compounds exhibit agonist activity at opiate receptor sites and are useful as analgesics.

  本文披露了N-戊二醛基取代的四肽酰胺及其药理学上可接受的盐。这些化合物是镇痛肽恩啡啶的类似物，其中第5位的蛋氨酸或亮氨酸被戊二醛基酰胺取代，第2位的甘氨酸被各种氨基酸残基取代。可选地，第1位的酪氨酸和第4位的苯丙氨酸可以被各种氨基酸残基取代。这些化合物在阿片受体位点表现出激动剂活性，并可用作镇痛剂。
• Cyclohexyl and phenyl substituted enkephalins
  申请人：G. D. Searle & Co.

  公开号：US04407746A1

  公开（公告）日：1983-10-04

  The invention discloses cyclohexyl and phenyl substituted enkephalin derivatives of the formula: ##STR1## Where R.sub.1, R.sub.2, R.sub.4, and R.sub.8 is hydrogen or alkyl of R.sub.3 is alkylthioalkyl or alkylsulfinylalkyl, X is: ##STR2## R.sub.5 is cyclohexylmethyl, phenylmethyl, optionally substituted by --NO.sub.2, R.sub.6 is cyclohexyl or phenyl optionally substituted by R.sub.7 and R.sub.7 is hydrogen, an alkyl ester of carboxylic acid or hydroxyalkyl and the pharmaceutically acceptable salts, which are useful as analgesic agents.

  本发明揭示了公式：##STR1##中的环己基和苯基取代的脑啡肽衍生物，其中R.sub.1，R.sub.2，R.sub.4和R.sub.8为氢或烷基，R.sub.3为烷基硫醇基或烷基亚砜基基，X为：##STR2##，R.sub.5为环己基甲基，苯基甲基，可选地取代为--NO.sub.2，R.sub.6为环己基或苯基，可选地取代为R.sub.7，R.sub.7为氢，羧酸酯的烷基或羟基烷基及其药学上可接受的盐，其作为镇痛剂。
• 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.
• Evidence of the preferential involvement of .mu.-receptors in analgesia using enkephalins highly selective for peripheral .mu. or .delta. receptors
  作者：Gilles Gacel、Marie Claude Fournie-Zaluski、Etienne Fellion、Bernard P. Roques

  DOI：10.1021/jm00142a002

  日期：1981.10

  In order to study the preferential involvement of mu or delta receptors in the analgesic effects of enkephalins, several peptides which selectively interact with these two kinds of receptors in peripheral organs were synthesized. The inhibitory potency on the electrically stimulated mouse vas deferens (delta receptors) of the short peptide Tyr-D-Ala-Gly-NH-CH(CH3)CH2CH(CH3)2 (6) is 2100 times lower (IC50 = 1220 nM) than that of the longer and more hydrophilic peptide Tyr-D-Ser-Gly-Phe-Leu-Thr (10) (IC50 = 0.58 nM). In contrast, the IC50 values of all the synthesized compounds on the guinea pig ileum assay (mu receptors) are in the same range (100-360 nM). Likewise, their analgesic activities in mice, measured on the hot-plate test after intracerebroventricular injection, are similar. Therefore, the dissociation between antinociceptive properties in mice and potencies on the mouse vas deferens unambiguously reflects a preferential implication of mu receptors in analgesia. The possible involvement of brain delta receptors in behavioral effects is discussed.
• MAZUR, R. H.;TYNER, D. A.;HALLINAN, E. A.
  作者：MAZUR, R. H.、TYNER, D. A.、HALLINAN, E. A.

  DOI：——

  日期：——