Boc-Phe-Lys(Z)-CH2Cl | 52780-89-9

• 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: Boc-Phe-Lys(Z)-CH2Cl
• 英文别名: Boc-Phe-Lys(Cbz)-CH2Cl；benzyl N-[(5S)-7-chloro-5-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]-6-oxoheptyl]carbamate
• CAS: 52780-89-9
• 化学式: C₂₉H₃₈ClN₃O₆
• 分子量: 560.09
• InChiKey: XYSNCEBWKCNNJT-ZEQRLZLVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  39
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Boc-Phe-Lys(Z)-CH2Cl 在 N-甲基吗啉 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 24.25h， 生成 naphth-2-oyl-Phe-Lys(Cbz)-CH2Cl
  参考文献：
  名称：

  Exploring the Sn Binding Pockets in Gingipains by Newly Developed Inhibitors:  Structure-Based Design, Chemistry, and Activity

  摘要：

  Arg-gingipains (Rgps) and Lys-gingipain (Kgp) are cysteine proteinases secreted by Porphyromonas gingivalis, the major pathogen implicated in periodontal disease. Gingipains are essential to the bacterium for its virulence and survival, and development of inhibitors targeting these proteins provides an approach to treat periodontal diseases. Here, we present the first example of structure-based design of gingipains inhibitors, with the use of the crystal structure of RgpB and the homology model of Kgp. Chloromethyl ketones were selected as suitable compounds to explore the specificity of the Sn binding region of both enzymes. Three series of inhibitors bearing Arg or Lys at P1 and different substituents at P2 and P3 were designed, synthesized, and tested. High potency (k(obs)/[I] similar to 10(7) M-1 s(-1)) was achieved for small ligands, such as the dipeptide analogues. The detailed analysis of Sn binding pockets revealed the molecular basis of inhibitory affinity and provided insight into the structure-activity relationship.

  DOI：

  10.1021/jm0600141
• 作为产物：
  描述：

  苄基叔丁基(7-重氮-6-氧代庚烷-1,5-二基)(S)-二氨基甲酸酯 在 N-甲基吗啉 、 盐酸 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 25.0h， 生成 Boc-Phe-Lys(Z)-CH2Cl
  参考文献：
  名称：

  Exploring the Sn Binding Pockets in Gingipains by Newly Developed Inhibitors:  Structure-Based Design, Chemistry, and Activity

  摘要：

  Arg-gingipains (Rgps) and Lys-gingipain (Kgp) are cysteine proteinases secreted by Porphyromonas gingivalis, the major pathogen implicated in periodontal disease. Gingipains are essential to the bacterium for its virulence and survival, and development of inhibitors targeting these proteins provides an approach to treat periodontal diseases. Here, we present the first example of structure-based design of gingipains inhibitors, with the use of the crystal structure of RgpB and the homology model of Kgp. Chloromethyl ketones were selected as suitable compounds to explore the specificity of the Sn binding region of both enzymes. Three series of inhibitors bearing Arg or Lys at P1 and different substituents at P2 and P3 were designed, synthesized, and tested. High potency (k(obs)/[I] similar to 10(7) M-1 s(-1)) was achieved for small ligands, such as the dipeptide analogues. The detailed analysis of Sn binding pockets revealed the molecular basis of inhibitory affinity and provided insight into the structure-activity relationship.

  DOI：

  10.1021/jm0600141

文献信息

• Amino Acids and Peptides. LII. Design and Synthesis of Opioid Mimetics Containing a Pyrazinone Ring and Examination of Their Opioid Receptor Binding Activity.
  作者：Yoshio OKADA、Masaki TSUKATANI、Hiroaki TAGUCHI、Toshio YOKOI、Sharon D. BRYANT、Lawrence H. LAZARUS

  DOI：10.1248/cpb.46.1374

  日期：——

  An amino group was introduced to the 3 or 6 position of a pyrazinone ring by cyclization of dipeptidyl chloromethyl ketones. Boc-Tyr-OH was coupled with the amino funciton, followed by removal of the Boc group to give pyrazinone ring-containing tyrosine derivatives. Of the various tyrosine derivatives prepared, 5-methyl-6-β-phenethyl-3-tyrosylaminobutyl-2(1H)-pyrazinone exhibited strong binding to the μ-opioid receptor with a Ki value of 55.8 nM and to the δ-opioid receptor with a Ki value of 2165 nM and with a Kiμ/Kiδ value of 0.026.

  通过二肽基氯甲基酮的环化反应，将氨基引入吡嗪酮环的3位或6位。将Boc-酪氨酸与氨基进行偶联，随后去除Boc保护基，得到含吡嗪酮环的酪氨酸衍生物。在制备的各种酪氨酸衍生物中，5-甲基-6-β-苯乙基-3-酪氨酰氨基丁基-2(1H)-吡嗪酮表现出对μ-阿片受体的强结合作用，其Ki值为55.8 nM，对δ-阿片受体的Ki值为2165 nM，且Kiμ/Kiδ值为0.026。