N-[(2R)-1-amino-6-[(1-amino-2-chloroethylidene)amino]-1-oxohexan-2-yl]benzamide | 1404060-43-0

• 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: N-[(2R)-1-amino-6-[(1-amino-2-chloroethylidene)amino]-1-oxohexan-2-yl]benzamide
• CAS: 1404060-43-0
• 化学式: C₁₅H₂₁ClN₄O₂
• 分子量: 324.81
• InChiKey: LXHVEMWJSQIYGG-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  、 2-氯-1-乙氧基乙胺 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 N-[(2R)-1-amino-6-[(1-amino-2-chloroethylidene)amino]-1-oxohexan-2-yl]benzamide
  参考文献：
  名称：

  d-Amino Acid-Based Protein Arginine Deiminase Inhibitors: Synthesis, Pharmacokinetics, and in Cellulo Efficacy

  摘要：

  The protein arginine deiminases (PADs) are known to play a crucial role in the onset and progression of multiple inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, and cancer. However, it is not known how each of the five PAD isozymes contributes to disease pathogenesis. As such, potent, selective, and bioavailable PAD inhibitors will be useful chemical probes to elucidate the specific roles of each isozyme. Because D-amino amino acids often possess enhanced in cellulo stability, and perhaps unique selectivities, we synthesized a series of D-amino acid analogues of our Pan-PAD inhibitor Cl-amicline, hypothesizing that this change would provide inhibitors with enhanced pharmacokinetic properties. Herein, we demonstrate that D-Cl-amidine and D-o-F-amidine are potent and highly selective inhibitors of PAD1. The pharmacokinetic properties of D-Cl-amidine were moderately improved over those of L-Cl-amidine, and this compound exhibited similar cell killing in a PAD1 expressing, triple-negative MDA-MB-231 breast cancer cell line. These inhibitors represent an important step in our efforts to develop stable, bioavailable, and highly selective inhibitors for all of the PAD isozymes.

  DOI：

  10.1021/ml300288d

文献信息

• <scp>d</scp>-Amino Acid-Based Protein Arginine Deiminase Inhibitors: Synthesis, Pharmacokinetics, and in Cellulo Efficacy
  作者：Kevin L. Bicker、Lynne Anguish、Alexander A. Chumanevich、Michael D. Cameron、Xiangli Cui、Erin Witalison、Venkataraman Subramanian、Xuesen Zhang、Alena P. Chumanevich、Lorne J. Hofseth、Scott A. Coonrod、Paul R. Thompson

  DOI：10.1021/ml300288d

  日期：2012.12.13

  The protein arginine deiminases (PADs) are known to play a crucial role in the onset and progression of multiple inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, and cancer. However, it is not known how each of the five PAD isozymes contributes to disease pathogenesis. As such, potent, selective, and bioavailable PAD inhibitors will be useful chemical probes to elucidate the specific roles of each isozyme. Because D-amino amino acids often possess enhanced in cellulo stability, and perhaps unique selectivities, we synthesized a series of D-amino acid analogues of our Pan-PAD inhibitor Cl-amicline, hypothesizing that this change would provide inhibitors with enhanced pharmacokinetic properties. Herein, we demonstrate that D-Cl-amidine and D-o-F-amidine are potent and highly selective inhibitors of PAD1. The pharmacokinetic properties of D-Cl-amidine were moderately improved over those of L-Cl-amidine, and this compound exhibited similar cell killing in a PAD1 expressing, triple-negative MDA-MB-231 breast cancer cell line. These inhibitors represent an important step in our efforts to develop stable, bioavailable, and highly selective inhibitors for all of the PAD isozymes.