(S)-2-{[(S)-1-(3,5-Dichloro-benzenesulfonyl)-pyrrolidine-2-carbonyl]-amino}-3-(4-hydroxy-phenyl)-propionic acid methyl ester | 425388-71-2

• 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-{[(S)-1-(3,5-Dichloro-benzenesulfonyl)-pyrrolidine-2-carbonyl]-amino}-3-(4-hydroxy-phenyl)-propionic acid methyl ester
• 英文别名: Bes(3,5-diCl)-Pro-Tyr-OMe；methyl (2S)-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoate
• CAS: 425388-71-2
• 化学式: C₂₁H₂₂Cl₂N₂O₆S
• 分子量: 501.387
• InChiKey: LZFRKRUOGUNPNC-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-2-{[(S)-1-(3,5-Dichloro-benzenesulfonyl)-pyrrolidine-2-carbonyl]-amino}-3-(4-hydroxy-phenyl)-propionic acid methyl ester 在 lithium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 生成 (S)-2-{[(S)-1-(3,5-Dichloro-benzenesulfonyl)-pyrrolidine-2-carbonyl]-amino}-3-(4-hydroxy-phenyl)-propionic acid
  参考文献：
  名称：

  Substituted N-(3,5-Dichlorobenzenesulfonyl)-l-prolyl-phenylalanine analogues as potent VLA-4 antagonists

  摘要：

  A series of substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl- and alpha-methyl-L-prolyl-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists. The compounds showed excellent potency with a wide variety of neutral, polar, electron withdrawing or donating groups on the phenylalanine ring (IC50 similar to I nM). Heteroaryl ring substitution for phenylalanine was also well tolerated. Pharmacokinetic studies in rat were performed on a representative set of compounds in both series. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00821-6
• 作为产物：
  描述：

  3,5-二氯苯磺酰氯 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (S)-2-{[(S)-1-(3,5-Dichloro-benzenesulfonyl)-pyrrolidine-2-carbonyl]-amino}-3-(4-hydroxy-phenyl)-propionic acid methyl ester
  参考文献：
  名称：

  The discovery of small molecule carbamates as potent dual α4β1/α4β7 integrin antagonists

  摘要：

  The alpha(4)beta(1) and alpha(4)beta(7) integrins are implicated in several inflammatory disease states. Systematic SAR studies of an alpha(4)beta(1)-specific arylsulfonyl-Pro-Tyr lead led to the identification of a new alpha(4)beta(7) binding site, best captured by O-carbamates of Tyr for this structural class. Several compounds showed a 200- to 400-fold improvement in alpha(4)beta(7) binding affinity while maintaining subnanomolar alpha(4)beta(1) activity, for example 21, VCAM-Ig alpha(4)beta(1) IC50 = 0.13 nM. VCAM-Ig alpha(4)beta(7) IC50 = 1.92 nM. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00710-7

文献信息

• Substituted N-(3,5-Dichlorobenzenesulfonyl)-l-prolyl-phenylalanine analogues as potent VLA-4 antagonists
  作者：Ihor E Kopka、David N Young、Linus S Lin、Richard A Mumford、Plato A Magriotis、Malcolm MacCoss、Sander G Mills、Gail Van Riper、Ermengilda McCauley、Linda E Egger、Usha Kidambi、John A Schmidt、Kathryn Lyons、Ralph Stearns、Stella Vincent、Adria Colletti、Zhen Wang、Sharon Tong、Junying Wang、Song Zheng、Karen Owens、Dorothy Levorse、William K Hagmann

  DOI：10.1016/s0960-894x(01)00821-6

  日期：2002.2

  A series of substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl- and alpha-methyl-L-prolyl-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists. The compounds showed excellent potency with a wide variety of neutral, polar, electron withdrawing or donating groups on the phenylalanine ring (IC50 similar to I nM). Heteroaryl ring substitution for phenylalanine was also well tolerated. Pharmacokinetic studies in rat were performed on a representative set of compounds in both series. (C) 2002 Elsevier Science Ltd. All rights reserved.
• The discovery of small molecule carbamates as potent dual α4β1/α4β7 integrin antagonists
  作者：Linda L. Chang、Quang Truong、Richard A. Mumford、Linda A. Egger、Usha Kidambi、Kathryn Lyons、Ermengilda McCauley、Gail Van Riper、Stella Vincent、John A. Schmidt、Malcolm MacCoss、William K. Hagmann

  DOI：10.1016/s0960-894x(01)00710-7

  日期：2002.1

  The alpha(4)beta(1) and alpha(4)beta(7) integrins are implicated in several inflammatory disease states. Systematic SAR studies of an alpha(4)beta(1)-specific arylsulfonyl-Pro-Tyr lead led to the identification of a new alpha(4)beta(7) binding site, best captured by O-carbamates of Tyr for this structural class. Several compounds showed a 200- to 400-fold improvement in alpha(4)beta(7) binding affinity while maintaining subnanomolar alpha(4)beta(1) activity, for example 21, VCAM-Ig alpha(4)beta(1) IC50 = 0.13 nM. VCAM-Ig alpha(4)beta(7) IC50 = 1.92 nM. (C) 2002 Elsevier Science Ltd. All rights reserved.