(2S)-2-amino-N-[(2R)-1-[[(4R,5S)-2-(2-amino-2-oxoethyl)-5-methyl-3-oxo-4,5-dihydro-1H-2-benzazepin-4-yl]amino]-1-oxopropan-2-yl]-3-(4-hydroxy-2,6-dimethylphenyl)propanamide;2,2,2-trifluoroacetic acid | 1333118-92-5

• 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: (2S)-2-amino-N-[(2R)-1-[[(4R,5S)-2-(2-amino-2-oxoethyl)-5-methyl-3-oxo-4,5-dihydro-1H-2-benzazepin-4-yl]amino]-1-oxopropan-2-yl]-3-(4-hydroxy-2,6-dimethylphenyl)propanamide;2,2,2-trifluoroacetic acid
• CAS: 1333118-92-5
• 化学式: C₂HF₃O₂*C₂₇H₃₅N₅O₅
• 分子量: 623.629
• InChiKey: ADURMEDVGTUTNN-ZPBMSFLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.13
• 重原子数：
  44
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  205
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2-[(4R,5R)-5-methyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxo-4,5-dihydro-1H-2-benzazepin-2-yl]acetic acid 、 三氟乙酸 在 氢氟酸 作用下， 以 苯甲醚 为溶剂， 反应 1.0h， 生成 (2S)-2-amino-N-[(2R)-1-[[(4R,5S)-2-(2-amino-2-oxoethyl)-5-methyl-3-oxo-4,5-dihydro-1H-2-benzazepin-4-yl]amino]-1-oxopropan-2-yl]-3-(4-hydroxy-2,6-dimethylphenyl)propanamide;2,2,2-trifluoroacetic acid
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Automated Docking of Constrained Analogues of the Opioid Peptide H-Dmt-d-Ala-Phe-Gly-NH₂ Using the 4- or 5-Methyl Substituted 4-Amino-1,2,4,5-tetrahydro-2-benzazepin-3-one Scaffold

  摘要：

  The Phe(3) residue of the N-terminal tetrapeptide of dermorphin (H-Dmt-D-Ala-Phe-Gly-NH2) was conformationally constrained using 4- or 5-methyl-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) stereoisomeric scaffolds. Several of the synthesized peptides were determined to be high affinity agonists for the mu opioid receptor (OPRM) with selectivity over the delta opioid receptor (OPRD). Interesting effects of the Aba configuration on ligand binding affinity were observed. H-Dmt-D-Ala-erythro-(4S,5S)-5-Me-Aba-Gly-NH2 9 and H-Dmt-threo-(4R,5S)-5-Me-Aba-Gly-NH2 12 exhibited subnanomolar affinity for OPRM, while they possess an opposite absolute configuration at position 4 of the Aba ring. However, in the 4-methyl substituted analogues, H-Dmt-D-Ala-(4R)-Me-Aba-Gly-NH2 14 was significantly more potent than the (4S)-derivative 13. These unexpected results were rationalized using the binding poses predicted by molecular docking simulations. Interestingly, H-Dmt-D-Ala-(4R)-Me-Aba-Gly-NH2 14 is proposed to bind in a different mode compared with the other analogues. Moreover, in contrast to Ac-4-Me-Aba-NH-Me, which adopts a beta-turn in solution and in the crystal structure, the binding mode of this analogue suggests an alternative receptor-bound conformation.

  DOI：

  10.1021/jm2003574