[2-(4-Carbamimidoyl-phenyl)-ethyl]-carbamic acid tert-butyl ester | 791839-12-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [2-(4-Carbamimidoyl-phenyl)-ethyl]-carbamic acid tert-butyl ester
• 英文别名: tert-Butyl 4-carbamimidoylphenethylcarbamate；tert-butyl N-[2-(4-carbamimidoylphenyl)ethyl]carbamate
• CAS: 791839-12-8
• 化学式: C₁₄H₂₁N₃O₂
• 分子量: 263.34
• InChiKey: LHRYHKVACQCZOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  88.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [2-(4-Carbamimidoyl-phenyl)-ethyl]-carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以85%的产率得到4-(2-aminoethyl)benzimidamide
  参考文献：
  名称：

  Design, synthesis, and evaluation of oxyanion-hole selective inhibitor substituents for the S1 subsite of factor Xa

  摘要：

  We have designed, synthesized, and evaluated the factor Xa inhibitory activities of p-amidinophenyl-sulfones, amines, and alcohols intended to take advantage of the polarity and hydrogen-bonding potential of the oxyanion hole region of the S1 specificity pocket. We demonstrate that placement of an anionic group within the oxyanion bole region of the catalytic site substantially enhances activity, with small flexible groups favored over bulkier ones. Ab initio pK(a) calculations suggest that the hydroxyl substituent frequently used for benzamidine moieties may be ionized to form an anionic group, consistent with the general trend. One nonamidine based substituent also shows promising activity. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.054
• 作为产物：
  描述：

  4-(2-硝基乙基)苯甲腈 在 盐酸 、 盐酸羟胺 、 乙酸酐 、 potassium carbonate 、 N,N-二异丙基乙胺 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 65.0 ℃ 、3.55 MPa 条件下， 反应 49.5h， 生成 [2-(4-Carbamimidoyl-phenyl)-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Increasing C-Terminal Hydrophobicity Improves the Cell Permeability and Antiproliferative Activity of PACE4 Inhibitors against Prostate Cancer Cell Lines

  摘要：

  The serine protease, PACE4, is a proprotein convertase that plays a substantial role in malignancy of prostate cancer. Our initial selective PACE4 inhibitor (Ac-LLLLRVKR-NH2) has evolved to the current lead compound C23 (Ac-DLeu-LLLRVK-Amba), which is active both in vitro and in vivo. By screening natural residues, except Cys, in C-terminal P1' position, it was established that increasing hydrophobicity was improving cell permeability, which was directly translated into PCa cells antiproliferative activity. This cell antiproliferation enhancement seems independent from effect of P1' residue on PACE4 affinity. Replacement of PI-Amba of C23 by Acpa ((S)-2-amino-3-(4-carbamimidoylphenyl)propanoic acid) followed by addition of tryptamine in P1' resulted in compound 32 exhibiting superior PCa cells antiproliferative activity over the reference compound C23 (3-fold). This study sheds light on key factors that improve cell penetrating property and antiproliferative activity of PACE4 inhibitors.

  DOI：

  10.1021/acs.jmedchem.8b01144

文献信息

• Increasing C-Terminal Hydrophobicity Improves the Cell Permeability and Antiproliferative Activity of PACE4 Inhibitors against Prostate Cancer Cell Lines
  作者：Vahid Dianati、Anna Kwiatkowska、Frédéric Couture、Roxane Desjardins、Yves L. Dory、Robert Day

  DOI：10.1021/acs.jmedchem.8b01144

  日期：2018.9.27

  The serine protease, PACE4, is a proprotein convertase that plays a substantial role in malignancy of prostate cancer. Our initial selective PACE4 inhibitor (Ac-LLLLRVKR-NH2) has evolved to the current lead compound C23 (Ac-DLeu-LLLRVK-Amba), which is active both in vitro and in vivo. By screening natural residues, except Cys, in C-terminal P1' position, it was established that increasing hydrophobicity was improving cell permeability, which was directly translated into PCa cells antiproliferative activity. This cell antiproliferation enhancement seems independent from effect of P1' residue on PACE4 affinity. Replacement of PI-Amba of C23 by Acpa ((S)-2-amino-3-(4-carbamimidoylphenyl)propanoic acid) followed by addition of tryptamine in P1' resulted in compound 32 exhibiting superior PCa cells antiproliferative activity over the reference compound C23 (3-fold). This study sheds light on key factors that improve cell penetrating property and antiproliferative activity of PACE4 inhibitors.
• Design, synthesis, and evaluation of oxyanion-hole selective inhibitor substituents for the S1 subsite of factor Xa
  作者：Sochanchingwung Rumthao、Oukseub Lee、Qi Sheng、WenTao Fu、Debbie C. Mulhearn、David Crich、Andrew D. Mesecar、Michael E. Johnson

  DOI：10.1016/j.bmcl.2004.07.054

  日期：2004.10

  We have designed, synthesized, and evaluated the factor Xa inhibitory activities of p-amidinophenyl-sulfones, amines, and alcohols intended to take advantage of the polarity and hydrogen-bonding potential of the oxyanion hole region of the S1 specificity pocket. We demonstrate that placement of an anionic group within the oxyanion bole region of the catalytic site substantially enhances activity, with small flexible groups favored over bulkier ones. Ab initio pK(a) calculations suggest that the hydroxyl substituent frequently used for benzamidine moieties may be ionized to form an anionic group, consistent with the general trend. One nonamidine based substituent also shows promising activity. (C) 2004 Elsevier Ltd. All rights reserved.