N-吡啶-3-基-L-苯丙氨酸酰胺 | 88932-75-6

• 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
• 中文名称: N-吡啶-3-基-L-苯丙氨酸酰胺
• 英文名称: 3-(L-phenylalanylamino)pyridine
• 英文别名: Phenylalanyl-3-aminopyridine；(2S)-2-amino-3-phenyl-N-pyridin-3-ylpropanamide
• CAS: 88932-75-6
• 化学式: C₁₄H₁₅N₃O
• mdl: MFCD13244764
• 分子量: 241.293
• InChiKey: DVQVJRFKIRFPAA-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  68
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-吡啶-3-基-L-苯丙氨酸酰胺 在 N-甲基吗啉 、 盐酸 、 氯甲酸异丁酯 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 ((S)-1-(4-Hydroxy-benzyl)-2-oxo-2-{(S)-2-[(S)-2-phenyl-1-(pyridin-3-ylcarbamoyl)-ethylcarbamoyl]-pyrrolidin-1-yl}-ethyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Development of Potent Bifunctional Endomorphin-2 Analogues with Mixed μ-/δ-Opioid Agonist and δ-Opioid Antagonist Properties

  摘要：

  The C terminus of endomorphin-2 (EM-2) analogues (Tyr-Pro-Phe-NH-X) was modified with aromatic, heteroaromatic, or aliphatic groups (X = phenethyl,benzyl, phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, tert-butyl, cyclohexyl, or adamantyl; 3-18) to study their effect on opioid activity. Only 9 (1-naphthyl), 11 (5-quinolyl), 16 (cyclohexyl), and 18 (2-adamantyl) exhibited mu-opioid receptor affinity in the nanomolar range (K-i = 2.41-6.59 nM), which, however, was 3- to 10-fold less than the parent peptide. Replacement of Tyr(1) by Dmt (2',6'-dimethyl-L-tyrosine) (19-32) exerted profound effects: (i) acquisition of high mu-opioid receptor affinity (K-i = 0.11-0.52 nM) except 23 (Ph); (ii) presence of potent functional mu-opioid receptor agonism (IC50 < 1 nM) for 19 ([Dmt(1)]EM-2), 27 (1-naphthyl), 29 (5-quinolyl), and 32 (5-isolquinolyl); (iii) association of weak delta-opioid antagonist activity (pA(2) = 5.41-7.18) except 19 ([Dmt(1)]EM-2), 20 (H), 27 (1-naphthyl), and in particular 29 (5-quinolyl) with its potent delta-agonism (IC50 = 0.62 nM, pA(2) = 5.88); (iv) production of antinociception after ic administration of 32 (5-isoquinolyl) in mice, a bioactivity absent in the corresponding Tyr(1) analogue (14); and (v) preferential cis orientation (cis/trans = 3:2 to 7:3) at the Dmt-Pro amide bond, in contrast to the Tyr-Pro amide trans orientation (cis/trans = 1:2 to 1:3). Thus, [Dmt(1)]EM-2 analogues with hydrophobic C-terminal extensions provide model compounds with potent mu-opioid receptor bioactivity and dual functional agonism.

  DOI：

  10.1021/jm030649p
• 作为产物：
  描述：

  phthaloyl-L-phenylalanyl chloride 在 一水合肼 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 12.0h， 生成 N-吡啶-3-基-L-苯丙氨酸酰胺
  参考文献：
  名称：

  Synthesis and analgesic activities of urea derivatives of α-amino-N-pyridyl benzene propanamide

  摘要：

  New urea L-phenyl alanine derivatives of 4-aminopyridine have been synthesized and evaluated for analgesic activity with the PBQ writhing test in mice and the Randall-Selitto test in rats. Potent oral activity (ID50 < 10 mg/kg) and good tolerance were found in alkyl, arylalkyl and carboxyalkyl urea derivatives. The analgesic activity was found to be totally dependent on the pyridine moiety and was at least partly inhibited by pretreatment with (alpha) methyltyrosine, as was the case for 4-aminopyridine. These compounds are therefore pharmacologically interesting as new analgesic derivatives of 4-aminopyridine. They have a higher oral activity and a better activity/tolerance profile.

  DOI：

  10.1016/0223-5234(94)90070-1

文献信息

• Design and synthesis of thiol containing inhibitors of matrix metalloproteinases
  作者：Cynthia A. Fink、J.Eric Carlson、Charles Boehm、Patricia McTaggart、Ying Qiao、John Doughty、Vishwas Ganu、Richard Melton、Ronald Goldberg

  DOI：10.1016/s0960-894x(98)00716-1

  日期：1999.1

  A series of thiol containing derivatives was prepared. Several of these compounds were found to inhibit matrix metalloproteinases 1, 3, and 9 with selectivity towards 3 and 9. Compounds 15, 20, and 22 were administered to rats orally at 75 mumol/kg. Drug levels of compounds 20 and 22 in the plasma were found to exceed the IC50 values for MMP 3 and 9 four hours after administration.

  制备了一系列含硫醇的衍生物。发现这些化合物中的几种抑制基质金属蛋白酶1、3和9，对3和9具有选择性。将化合物15、20和22以75μmol/ kg口服给予大鼠。发现给药后四小时血浆中化合物20和22的药物水平超过MMP 3和9的IC50值。
• Metal-driven folding and assembly of a minimal β-sheet into a 3D-porous honeycomb framework
  作者：Nikhil Bajpayee、Salil Pophali、Thangavel Vijayakanth、Shyamapada Nandi、Aamod V. Desai、Vinod Kumar、Rahul Jain、Santu Bera、Linda J. W. Shimon、Rajkumar Misra

  DOI：10.1039/d3cc05185d

  日期：——

  Metal-mediated supramolecular assembly of a minimal β-sheet peptide revealed a hetero terminal peptide assembled into a 3D porous honeycomb framework.

  金属介导的最小 β 片肽超分子组装揭示了异端肽组装成三维多孔蜂巢框架的过程。
• Hydrogelation Through Self-Assembly of Fmoc-Peptide Functionalized Cationic Amphiphiles: Potent Antibacterial Agent
  作者：Sisir Debnath、Anshupriya Shome、Dibyendu Das、Prasanta Kumar Das

  DOI：10.1021/jp909520w

  日期：2010.4.8

  The present work reports a new class of antibacterial hydrogelators based on anti-inflammatory N-fluorenyl-9-methoxycarbonyl (Fmoc) amino acid/peptides functionalized cationic amphiphiles. These positively charged hydrogelators were rationally designed and developed by the incorporation of a pyridinium moiety at the C-terminal of Fmoc amino acid/peptides, because the pyridinium-based amphiphiles are a known antibacterial agent due to their cell membrane penetration properties. The Fmoc amino acid/peptide-based cationic amphiphiles efficiently gelate (minimum gelation concentration similar to 0.6-2.2%, w/v) water at room temperature. Judicious variation of amino acid and their sequences revealed the architectural dependence of the molecules on their gelation ability. Several microscopic techniques like field-emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM) were used to obtain the visual insight of the morphology of the gel network. A number of spectroscopic techniques like circular dichroism, FTIR, photoluminescence, and XRD were utilized to know the involvement of several noncovalent interactions and participation of the different segments of the molecules during gelation. Spectroscopic results showed that the pi-pi interaction and intermolecular hydrogen bonding are the major responsible factors for the self-assembled gelation process that are oriented through an antiparallel beta-sheet arrangement of the peptide backbone. These Fmoc-based cationic molecules exhibited efficient antibacterial activity against both Gram-positive and Gram-negative bacteria.
• Development of Potent Bifunctional Endomorphin-2 Analogues with Mixed μ-/δ-Opioid Agonist and δ-Opioid Antagonist Properties
  作者：Yoshio Fujita、Yuko Tsuda、Tingyou Li、Takashi Motoyama、Motohiro Takahashi、Yoshiro Shimizu、Toshio Yokoi、Yusuke Sasaki、Akihiro Ambo、Atsuko Kita、Yunden Jinsmaa、Sharon D. Bryant、Lawrence H. Lazarus、Yoshio Okada

  DOI：10.1021/jm030649p

  日期：2004.7.1

  The C terminus of endomorphin-2 (EM-2) analogues (Tyr-Pro-Phe-NH-X) was modified with aromatic, heteroaromatic, or aliphatic groups (X = phenethyl,benzyl, phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, tert-butyl, cyclohexyl, or adamantyl; 3-18) to study their effect on opioid activity. Only 9 (1-naphthyl), 11 (5-quinolyl), 16 (cyclohexyl), and 18 (2-adamantyl) exhibited mu-opioid receptor affinity in the nanomolar range (K-i = 2.41-6.59 nM), which, however, was 3- to 10-fold less than the parent peptide. Replacement of Tyr(1) by Dmt (2',6'-dimethyl-L-tyrosine) (19-32) exerted profound effects: (i) acquisition of high mu-opioid receptor affinity (K-i = 0.11-0.52 nM) except 23 (Ph); (ii) presence of potent functional mu-opioid receptor agonism (IC50 < 1 nM) for 19 ([Dmt(1)]EM-2), 27 (1-naphthyl), 29 (5-quinolyl), and 32 (5-isolquinolyl); (iii) association of weak delta-opioid antagonist activity (pA(2) = 5.41-7.18) except 19 ([Dmt(1)]EM-2), 20 (H), 27 (1-naphthyl), and in particular 29 (5-quinolyl) with its potent delta-agonism (IC50 = 0.62 nM, pA(2) = 5.88); (iv) production of antinociception after ic administration of 32 (5-isoquinolyl) in mice, a bioactivity absent in the corresponding Tyr(1) analogue (14); and (v) preferential cis orientation (cis/trans = 3:2 to 7:3) at the Dmt-Pro amide bond, in contrast to the Tyr-Pro amide trans orientation (cis/trans = 1:2 to 1:3). Thus, [Dmt(1)]EM-2 analogues with hydrophobic C-terminal extensions provide model compounds with potent mu-opioid receptor bioactivity and dual functional agonism.
• Synthesis and analgesic activities of urea derivatives of α-amino-N-pyridyl benzene propanamide
  作者：E Sartori、F Camy、JM Teulon、F Camborde、J Meignen、F Hertz、A Cloarec

  DOI：10.1016/0223-5234(94)90070-1

  日期：1994.1

  New urea L-phenyl alanine derivatives of 4-aminopyridine have been synthesized and evaluated for analgesic activity with the PBQ writhing test in mice and the Randall-Selitto test in rats. Potent oral activity (ID50 < 10 mg/kg) and good tolerance were found in alkyl, arylalkyl and carboxyalkyl urea derivatives. The analgesic activity was found to be totally dependent on the pyridine moiety and was at least partly inhibited by pretreatment with (alpha) methyltyrosine, as was the case for 4-aminopyridine. These compounds are therefore pharmacologically interesting as new analgesic derivatives of 4-aminopyridine. They have a higher oral activity and a better activity/tolerance profile.