3-(3-benzyl-ureido)-2-{[1-(3,5-dimethyl-benzenesulfonyl)-pyrrolidine-2-carbonyl]-amino}-propionic acid

• 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: 3-(3-benzyl-ureido)-2-{[1-(3,5-dimethyl-benzenesulfonyl)-pyrrolidine-2-carbonyl]-amino}-propionic acid
• 英文别名: prolyl-2,3-diaminopropionic acid (DAP) scaffold, 19；(2S)-3-(benzylcarbamoylamino)-2-[[(2S)-1-(3,5-dimethylphenyl)sulfonylpyrrolidine-2-carbonyl]amino]propanoic acid
• 化学式: C₂₄H₃₀N₄O₆S
• 分子量: 502.591
• InChiKey: ACPGEFYNFSMQSQ-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  153
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3,5-二甲基苯磺酰基氯 、 Fmoc-L-脯氨酸 、 异氰酸苄酯 、 Fmoc-3-[[(烯丙氧基)羰基]氨基]-L-丙氨酸 生成 3-(3-benzyl-ureido)-2-{[1-(3,5-dimethyl-benzenesulfonyl)-pyrrolidine-2-carbonyl]-amino}-propionic acid
  参考文献：
  名称：

  Small Molecule Inhibitors of Integrin α2β1

  摘要：

  Interactions between the integrin, alpha 21, and extracellular matrix (ECM), particularly collagen, play a pivotal role in platelet adhesion and thrombus formation. Platelets interact with collagen in the subendothelial matrix that is exposed by vascular damage. To evaluate the potential of alpha 2 beta 1 inhibitors for anticancer and antithrombotic applications, we have developed a series of small molecule inhibitors of this integrin based on a prolyl-2,3-diaminopropionic acid (DAP) scaffold using solid-phase parallel synthesis. A benzene-sulfonamide substituent at the N-terminus of the dipepetide and a benzyl urea at the DAP side chain resulted in tight and highly selective inhibition of alpha 2 beta 1-mediated adhesion of human platelets and other cells to collagen.

  DOI：

  10.1021/jm070252b

文献信息

• INHIBITORS OF THE ALPHA2BETA1/GPIa-IIA INTEGRIN
  申请人：Degrado William F.

  公开号：US20090233968A1

  公开（公告）日：2009-09-17

  Novel compounds inhibiting the integrin α2β1/GPIa-IIa receptor are disclosed. Also disclosed are pharmaceutical compositions containing the compounds, as well as methods of their therapeutic use. The compounds disclosed are useful, inter alia, as inhibitors of integrin α2β1/GPIa-IIa-mediated activity.
• US8258159B2
  申请人：——

  公开号：US8258159B2

  公开（公告）日：2012-09-04
• [EN] INHIBITORS OF THE a2ß1/GPIa-IIa INTEGRIN<br/>[FR] INHIBITEURS D'INTEGRINE A2B1/GPIA-IIA
  申请人：UNIV PENNSYLVANIA

  公开号：WO2006133338A1

  公开（公告）日：2006-12-14

  [EN] Novel compounds inhibiting the integrin a2ßl/GPIa-IIa receptor are disclosed. Also disclosed are pharmaceutical compositions containing the compounds, as well as methods of their therapeutic use. The compounds disclosed are useful, inter alia, as inhibitors of integrin a2ßl/GPIa-IIa-mediated activity.
  [FR] La présente invention a trait à de nouveaux composés inhibiteurs du récepteur de l'intégrine a2ßl/GPIa-IIa. L'invention a également trait à des compositions pharmaceutiques contenant les composés, ainsi qu'à leurs procédés d'utilisation thérapeutique. Les composés de l'invention sont utiles, entre autres, comme inhibiteurs de l'activité médiée par l'intégrine a2ßl/GPIa-IIa.
• Small Molecule Inhibitors of Integrin α2β1
  作者：Sungwook Choi、Gaston Vilaire、Cezary Marcinkiewicz、Jeffrey D. Winkler、Joel S. Bennett、William F. DeGrado

  DOI：10.1021/jm070252b

  日期：2007.11.1

  Interactions between the integrin, alpha 21, and extracellular matrix (ECM), particularly collagen, play a pivotal role in platelet adhesion and thrombus formation. Platelets interact with collagen in the subendothelial matrix that is exposed by vascular damage. To evaluate the potential of alpha 2 beta 1 inhibitors for anticancer and antithrombotic applications, we have developed a series of small molecule inhibitors of this integrin based on a prolyl-2,3-diaminopropionic acid (DAP) scaffold using solid-phase parallel synthesis. A benzene-sulfonamide substituent at the N-terminus of the dipepetide and a benzyl urea at the DAP side chain resulted in tight and highly selective inhibition of alpha 2 beta 1-mediated adhesion of human platelets and other cells to collagen.