N-EtPhe(4-F)-NH2 | 78981-74-5

• 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-EtPhe(4-F)-NH2
• 英文别名: (2S)-2-(ethylamino)-3-(4-fluorophenyl)propanamide
• CAS: 78981-74-5
• 化学式: C₁₁H₁₅FN₂O
• 分子量: 210.251
• InChiKey: LIZUVCPFZKSVHR-JTQLQIEISA-N

物化性质

• 熔点：
  117.5-118.5 °C(Solvent: Diethyl ether)
• 沸点：
  369.8±37.0 °C(Predicted)
• 密度：
  1.130±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-EtPhe(4-F)-NH2 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 、 溶剂黄146 、 苯甲醚 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 81.0h， 生成 (R)-5-Guanidino-2-[(S)-2-guanidino-3-(4-hydroxy-phenyl)-propionylamino]-pentanoic acid ({[(S)-1-carbamoyl-2-(4-fluoro-phenyl)-ethyl]-ethyl-carbamoyl}-methyl)-amide; compound with acetic acid
  参考文献：
  名称：

  Peripherally acting enkephalin analogs. 2. Polar tri- and tetrapeptides

  摘要：

  The design, synthesis, and biological activity of a series of D-Arg2-enkephalin-derived tetrapeptide amides and tripeptide aralkylamides are reported. These polar analogues were designed to be excluded from the central nervous system with their action thus limited to peripheral opioid receptors. The effects of the nature of the aromatic ring, aryl ring substitution, and aralkylamine chain length on activity were investigated; in a number of cases the N-terminal amino group of Tyr1 was converted to a guanidino group to further increase hydrophilicity. The peptides were all synthesized by classical solution methodology. The opioid activity of the peptides was assessed in vitro on the guinea pig ileum and their antinociceptive activity was determined in vivo in chemically induced writhing models (peripheral activity) and in the hot-plate test (central activity), in rodents. That the analgesic effects were predominantly mediated in the periphery was demonstrated by antagonism of antinociception by the peripheral opioid antagonist N-methylnalorphine and by comparison of the activities in the writhing and hot-plate tests. As a class, the tetrapeptides were more potent than the tripeptides; N alpha-amidination generally increased activity. A number of compounds exhibited very potent opioid activity and had the desired pharmacological profile, indicating a high degree of peripheral selectivity.

  DOI：

  10.1021/jm00125a028
• 作为产物：
  描述：

  BOC-L-4-氟苯丙氨酸 在 N-甲基吗啉 、 盐酸 、 氨 、 碳酸氢钠 、 溶剂黄146 、 苯甲醚 、 氯甲酸异丁酯 作用下， 以 乙醇 为溶剂， 反应 8.08h， 生成 N-EtPhe(4-F)-NH2
  参考文献：
  名称：

  Peripherally acting enkephalin analogs. 2. Polar tri- and tetrapeptides

  摘要：

  The design, synthesis, and biological activity of a series of D-Arg2-enkephalin-derived tetrapeptide amides and tripeptide aralkylamides are reported. These polar analogues were designed to be excluded from the central nervous system with their action thus limited to peripheral opioid receptors. The effects of the nature of the aromatic ring, aryl ring substitution, and aralkylamine chain length on activity were investigated; in a number of cases the N-terminal amino group of Tyr1 was converted to a guanidino group to further increase hydrophilicity. The peptides were all synthesized by classical solution methodology. The opioid activity of the peptides was assessed in vitro on the guinea pig ileum and their antinociceptive activity was determined in vivo in chemically induced writhing models (peripheral activity) and in the hot-plate test (central activity), in rodents. That the analgesic effects were predominantly mediated in the periphery was demonstrated by antagonism of antinociception by the peripheral opioid antagonist N-methylnalorphine and by comparison of the activities in the writhing and hot-plate tests. As a class, the tetrapeptides were more potent than the tripeptides; N alpha-amidination generally increased activity. A number of compounds exhibited very potent opioid activity and had the desired pharmacological profile, indicating a high degree of peripheral selectivity.

  DOI：

  10.1021/jm00125a028

文献信息

• Study of intramolecular aminolysis in peptides containing N-alkylamino acids at position 2
  作者：Vladimir V. Ryakhovsky、Andrey S. Ivanov

  DOI：10.1016/j.tet.2012.06.056

  日期：2012.9

  IA more strongly than aqueous ammonia, while tertiary amines were less effective. Peptides with methionine-S-oxide residues were more labile than the unoxidized analogs, suggesting intramolecular assistance of the S-oxide group in aminolysis. Surprisingly, intermediate compounds of the formula Boc–Met-MeXaa-Sar–NHR underwent rapid cleavage (endopeptolysis) upon attempted acidolytic deprotection.

  许多肽和蛋白质，含Ñ α -烷基氨基酸（包括脯氨酸）在所述第二位置，很容易发生分子内氨解（IA）具有N-末端二肽序列的消除2,5-二酮哌嗪（DKP）。我们合成了一系列短肽，在2位含有N-烷基氨基酸，并研究了它们在乙酸和胺存在下的稳定性。在第二侧链和第三个氨基酸残基，并且烷基化在存在Ñ α第三氨基酸残基的减慢IA。ñ α-第一个氨基酸残基中的烷基残基仅在包含三个或更多个残基的肽中阻碍IA。第一个氨基酸的侧链没有显着影响裂解率。乙酸比氨水对IA的促进作用更强，而叔胺的效果较差。具有蛋氨酸-S-氧化物残基的肽比未氧化的类似物更不稳定，这表明在氨解中S-氧化物基团的分子内辅助。出人意料的是，式Boc–Met-MeXaa-Sar–NHR的中间体化合物在尝试进行酸解脱保护后迅速裂解（内肽水解）。
• Pharmacologically active peptides, their preparation and pharmaceutical compositions containing them
  申请人：ELI LILLY AND COMPANY

  公开号：EP0030845A2

  公开（公告）日：1981-06-24

  Compounds of the formula and pharmaceutically acceptable non-toxic acid addition salts thereof, in which Land D define the chirality; R1 is hydrogen or C1-C3 primary alkyl; R2 is C1-C4 primary or secondary alkyl, allyl, cyclopropylmethyl, C1-C2 hydroxyalkyl, or -(CH2)m-U-CH3 in which U is -S- or S-0 and mis 1 or 2; R3 is hydrogen, C1-C4 primary or secondary alkyl, cyclopropylmethyl, allyl or propargyl; and in which R, is hydrogen, acetyl, or acetoxymethyl and R5 is C1-C3 alkyl; are useful analgesic agents. These compounds are prepared by deblocking the correspondingly blocked compound of formula I with a deblocking agent.

  式化合物 及其药学上可接受的无毒酸加成盐，其中 Land D 定义了手性； R1 是氢或 C1-C3 伯烷基； R2 是 C1-C4 伯烷基或仲烷基、 烯丙基、环丙基甲基、C1-C2 羟基烷基或-(CH2)m-U-CH3，其中 U 是-S-或 S-0 且误为 1 或 2；R3 是氢、C1-C4 伯或仲烷基、环丙基甲基、烯丙基或丙炔基；以及 其中 R，是氢、乙酰基或乙酰氧甲基，R5 是 C1-C3 烷基；这些都是有用的镇痛剂。这些化合物的制备方法是用解嵌剂对相应的式 I 嵌段化合物进行解嵌。
• HARDY, GEORGE W.;LOWE, LAWRENCE A.;MILLS, GAIL;PANG, YIH SANG;SIMPKIN, DE+, J. MED. CHEM., 32,(1989) N, C. 1108-1118
  作者：HARDY, GEORGE W.、LOWE, LAWRENCE A.、MILLS, GAIL、PANG, YIH SANG、SIMPKIN, DE+

  DOI：——

  日期：——
• Peripherally acting enkephalin analogs. 2. Polar tri- and tetrapeptides
  作者：George W. Hardy、Lawrence A. Lowe、Gail Mills、Pang Yih Sang、Dean S. A. Simpkin、Rhonda L. Follenfant、Clare Shankley、Terence W. Smith

  DOI：10.1021/jm00125a028

  日期：1989.5

  The design, synthesis, and biological activity of a series of D-Arg2-enkephalin-derived tetrapeptide amides and tripeptide aralkylamides are reported. These polar analogues were designed to be excluded from the central nervous system with their action thus limited to peripheral opioid receptors. The effects of the nature of the aromatic ring, aryl ring substitution, and aralkylamine chain length on activity were investigated; in a number of cases the N-terminal amino group of Tyr1 was converted to a guanidino group to further increase hydrophilicity. The peptides were all synthesized by classical solution methodology. The opioid activity of the peptides was assessed in vitro on the guinea pig ileum and their antinociceptive activity was determined in vivo in chemically induced writhing models (peripheral activity) and in the hot-plate test (central activity), in rodents. That the analgesic effects were predominantly mediated in the periphery was demonstrated by antagonism of antinociception by the peripheral opioid antagonist N-methylnalorphine and by comparison of the activities in the writhing and hot-plate tests. As a class, the tetrapeptides were more potent than the tripeptides; N alpha-amidination generally increased activity. A number of compounds exhibited very potent opioid activity and had the desired pharmacological profile, indicating a high degree of peripheral selectivity.