4-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[1-((4-methylsulfonyl)butyl) cyclopentyl]carbonyl]-L-phenylalanine methyl ester | 220878-64-8

• 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: 4-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[1-((4-methylsulfonyl)butyl) cyclopentyl]carbonyl]-L-phenylalanine methyl ester
• 英文别名: methyl (2S)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[[1-(4-methylsulfonylbutyl)cyclopentanecarbonyl]amino]propanoate
• CAS: 220878-64-8
• 化学式: C₂₈H₃₄Cl₂N₂O₆S
• 分子量: 597.56
• InChiKey: UOKPKRFJJCQVTG-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[1-((4-methylsulfonyl)butyl) cyclopentyl]carbonyl]-L-phenylalanine methyl ester 在 sodium borohydrid 、 ammonium chloride 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 为溶剂， 以0.89 g (47%)的产率得到4-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[1-((4-methylsulfonyl) butyl)cyclopentyl]carbonyl]-L-phenylalanine alcohol
  参考文献：
  名称：

  Phenylalaninol derivatives

  摘要：

  已经发现以下化合物的公式：和其药学上可以接受的盐和酯，其中X和Y的定义如下，比其衍生的相应羧酸更容易被吸收且更具生物利用度，两者都是VCAM-1与VLA-4在体内结合的有效抑制剂，并且在治疗炎症性疾病中有用，其中这种结合作用会引发炎症。

  公开号：

  US06420600B1
• 作为产物：
  描述：

  环戊烷甲酸甲酯 在 sodium hydroxide 、 双氧水 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 生成 4-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[1-((4-methylsulfonyl)butyl) cyclopentyl]carbonyl]-L-phenylalanine methyl ester
  参考文献：
  名称：

  N-Cycloalkanoyl-l-Phenylalanine Derivatives as VCAM/VLA-4 Antagonists

  摘要：

  A systematic structure-activity relationship investigation of the lead compound I resulted the identification of several N-[(substituted alkyl)cycloalkanoyl]-4-[((2,6-dichlorophenyl)carbonyl)amino]-L-phenylalanine derivatives as potent VCAM/VLA-4 antagonists. The data are consistent with a model of these compounds in which these alkanoylphenylalanines reside in a compact gauche (-) bioactive conformation. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00386-4

文献信息

• Phenylalaninol derivatives
  申请人：Hoffman-La Roche Inc.

  公开号：US06420600B1

  公开（公告）日：2002-07-16

  It has been discovered that compounds of the formula: and the pharmaceutically acceptable salts and esters thereof wherein X and Y are as defined below, are more readily absorbed and more bioavailable than the corresponding carboxylic acids from which they are derived, both of which are effective inhibitors of the binding of VCAM-1 to VLA-4 in vivo and are useful in treating inflammation in inflammatory diseases in which such binding acts to bring on the inflammation.

  已经发现以下化合物的公式：和其药学上可以接受的盐和酯，其中X和Y的定义如下，比其衍生的相应羧酸更容易被吸收且更具生物利用度，两者都是VCAM-1与VLA-4在体内结合的有效抑制剂，并且在治疗炎症性疾病中有用，其中这种结合作用会引发炎症。
• PHENYLALANINOL DERIVATIVES
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1154987B1

  公开（公告）日：2004-04-21
• US6420600B1
  申请人：——

  公开号：US6420600B1

  公开（公告）日：2002-07-16
• [EN] PHENYLALANINOL DERIVATIVES<br/>[FR] DÉRIVÉS DE PHÉNYLALANINOL
  申请人：HOFFMANN LA ROCHE

  公开号：WO2000048988A1

  公开（公告）日：2000-08-24

  Compounds of formula (1) and the pharmaceutically acceptable salts and esters thereof wherein X and Y are as defined in the specification, are effective inhibitors of the binding of VCAM-1 to VLA-4 in vivo and are useful in treating inflammation in inflammatory diseases in which such binding acts to bring on the inflammation.
• N-Cycloalkanoyl-l-Phenylalanine Derivatives as VCAM/VLA-4 Antagonists
  作者：Achyutharao Sidduri、Jefferson W Tilley、Kenneth Hull、Jian Ping Lou、Gerry Kaplan、Allen Sheffron、Li Chen、Robert Campbell、Robert Guthrie、Tai-Nan Huang、Nicholas Huby、Karen Rowan、Virginia Schwinge、Louis M Renzetti

  DOI：10.1016/s0960-894x(02)00386-4

  日期：2002.9

  A systematic structure-activity relationship investigation of the lead compound I resulted the identification of several N-[(substituted alkyl)cycloalkanoyl]-4-[((2,6-dichlorophenyl)carbonyl)amino]-L-phenylalanine derivatives as potent VCAM/VLA-4 antagonists. The data are consistent with a model of these compounds in which these alkanoylphenylalanines reside in a compact gauche (-) bioactive conformation. (C) 2002 Elsevier Science Ltd. All rights reserved.