N-[(3,5-dichlorophenyl)sulfonyl]-4(R)-azido-(L)-proline | 1160824-85-0

• 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-[(3,5-dichlorophenyl)sulfonyl]-4(R)-azido-(L)-proline
• 英文别名: (2S,4R)-4-azido-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carboxylic acid
• CAS: 1160824-85-0
• 化学式: C₁₁H₁₀Cl₂N₄O₄S
• 分子量: 365.197
• InChiKey: GMGGBXJYVSKDPI-SCZZXKLOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  97.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-amino-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoate hydrochloride 、 N-[(3,5-dichlorophenyl)sulfonyl]-4(R)-azido-(L)-proline 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-{N-[(3,5-dichlorophenyl)sulfonyl]-4(R)-azido-(L)-prolyl}-4-[(3',5'-dichloro-isonicotinoyl)amino]-(L)-phenylalanine methyl ester
  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
• 作为产物：
  描述：

  N-[(3,5-dichlorophenyl)sulfonyl]-4(R)-azido-(L)-proline methyl ester 在 甲醇 、 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以1.5 g的产率得到N-[(3,5-dichlorophenyl)sulfonyl]-4(R)-azido-(L)-proline
  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.