N-{N-[(3,5-dichlorophenyl)sulfonyl]-4(R)-azetidinyl-(L)-prolyl}-4-[(3',5'-dichloroisonicotinoyl)amino]-(L)-phenylalanine | 462123-40-6

• 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
• 英文名称: N-{N-[(3,5-dichlorophenyl)sulfonyl]-4(R)-azetidinyl-(L)-prolyl}-4-[(3',5'-dichloroisonicotinoyl)amino]-(L)-phenylalanine
• 英文别名: (2S)-2-[[(2S,4R)-4-(azetidin-1-yl)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid
• CAS: 462123-40-6
• 化学式: C₂₉H₂₇Cl₄N₅O₆S
• 分子量: 715.441
• InChiKey: DWWRBBBYJCGWGH-YNJKOYDBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  157
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  ethyl (2S)-2-[[(2S,4R)-4-(azetidin-1-yl)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoate 在 lithium hydrochloride monohydrate 、 水 作用下， 以 乙腈 为溶剂， 生成 N-{N-[(3,5-dichlorophenyl)sulfonyl]-4(R)-azetidinyl-(L)-prolyl}-4-[(3',5'-dichloroisonicotinoyl)amino]-(L)-phenylalanine
  参考文献：
  名称：

  Discovery of N-{N-[(3-Cyanophenyl)sulfonyl]-4(R)-cyclobutylamino-(l)-prolyl}-4-[(3′,5′-dichloroisonicotinoyl)amino]-(l)-phenylalanine (MK-0668), an Extremely Potent and Orally Active Antagonist of Very Late Antigen-4

  摘要：

  Extremely potent very late antigen-4 (VLA-4) antagonists with picomolar, whole blood activity and slow dissociation rates were discovered by incorporating an amino substituent on the proline fragment of the initial lead structure. This level of potency against the unactivated form of VLA-4 was shown to be sufficient to overcome the poor pharmacokinetic profiles typical of this class of VLA-4 antagonists, and sustained activity as measured by receptor occupancy was achieved in preclinical species after oral dosing.

  DOI：

  10.1021/jm900257b

文献信息

• Discovery of <i>N</i>-{<i>N</i>-[(3-Cyanophenyl)sulfonyl]-4(<i>R</i>)-cyclobutylamino-(<scp>l</scp>)-prolyl}-4-[(3′,5′-dichloroisonicotinoyl)amino]-(<scp>l</scp>)-phenylalanine (MK-0668), an Extremely Potent and Orally Active Antagonist of Very Late Antigen-4
  作者：Linus S. Lin、Thomas Lanza、James P. Jewell、Ping Liu、Carrie Jones、Gerard R. Kieczykowski、Kelly Treonze、Qian Si、Salony Manior、Gloria Koo、Xinchun Tong、Junying Wang、Anne Schuelke、James Pivnichny、Regina Wang、Conrad Raab、Stella Vincent、Philip Davies、Malcolm MacCoss、Richard A. Mumford、William K. Hagmann

  DOI：10.1021/jm900257b

  日期：2009.6.11

  Extremely potent very late antigen-4 (VLA-4) antagonists with picomolar, whole blood activity and slow dissociation rates were discovered by incorporating an amino substituent on the proline fragment of the initial lead structure. This level of potency against the unactivated form of VLA-4 was shown to be sufficient to overcome the poor pharmacokinetic profiles typical of this class of VLA-4 antagonists, and sustained activity as measured by receptor occupancy was achieved in preclinical species after oral dosing.