(S)-2-((2S,4R)-4-(azetidin-1-yl)-1-(3-cyanophenylsulfonyl)pyrrolidine-2-carboxamido)-3-(4-(3,5-dichloroisonicotinamido)phenyl)propanoic acid | 1206805-64-2

• 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: (S)-2-((2S,4R)-4-(azetidin-1-yl)-1-(3-cyanophenylsulfonyl)pyrrolidine-2-carboxamido)-3-(4-(3,5-dichloroisonicotinamido)phenyl)propanoic acid
• 英文别名: (2S)-2-[[(2S,4R)-4-(azetidin-1-yl)-1-(3-cyanophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid
• CAS: 1206805-64-2
• 化学式: C₃₀H₂₈Cl₂N₆O₆S
• 分子量: 671.561
• InChiKey: ZVYKWIXTSCOLQS-NYMACZPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  181
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  ethyl (2S)-2-[[(2S,4R)-4-(azetidin-1-yl)-1-(3-cyanophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoate 在 水 、 lithium hydroxide 作用下， 以 乙腈 为溶剂， 生成 (S)-2-((2S,4R)-4-(azetidin-1-yl)-1-(3-cyanophenylsulfonyl)pyrrolidine-2-carboxamido)-3-(4-(3,5-dichloroisonicotinamido)phenyl)propanoic acid
  参考文献：
  名称：

  Discovery of N-{N-[(3-cyanobenzene) sulfonyl]-4(R)-(3,3-difluoropiperidin-1-yl)-(l)-prolyl}-4-[(3′,5′-dichloro-isonicotinoyl) amino]-(l)-phenylalanine (MK-0617), a highly potent and orally active VLA-4 antagonist

  摘要：

  A series of prolyl-N-isonicotinoyl-(L)-4-aminophenylalanine derivatives substituted at the proline 4-position with cyclic amines was evaluated as VLA-4 antagonists. The ring size and presence or absence of fluorine affected potency and receptor occupancy. The analog with 3,3-difluoropiperidine at the proline 4-position (13) was the most potent compound and had very good duration of receptor occupancy in vitro. The ethyl ester prodrug of 13 demonstrated excellent receptor occupancy after oral dosing in rats. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.111

文献信息

• Heterocycle-substituted proline dipeptides as potent VLA-4 antagonists
  作者：Thomas S. Reger、Jasmine Zunic、Nicholas Stock、Bowei Wang、Nicholas D. Smith、Benito Munoz、Mitchell D. Green、Michael F. Gardner、Joyce P. James、Weichao Chen、Kenneth Alves、Qian Si、Kelly M. Treonze、Russell B. Lingham、Richard A. Mumford

  DOI：10.1016/j.bmcl.2009.12.009

  日期：2010.2

  A variety of N-linked tertiary amines and heteroarylamines were examined at the 4-position of sulfonylated proline dipeptides in order to improve VLA-4 receptor off-rates and overcome the issue of CYP3A4 time-dependent inhibition of ester prodrugs. A tight-binding inhibitor 5j with a long off-rate provided sustained receptor occupancy despite poor oral pharmacokinetics. (C) 2009 Elsevier Ltd. All rights reserved.