3-N-(9-fluorenylmethoxycarbonyl)-amino-2-cyclohexylpropionic acid | 683217-61-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 3-N-(9-fluorenylmethoxycarbonyl)-amino-2-cyclohexylpropionic acid
• 英文别名: 2-Cyclohexyl-3-(9h-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 683217-61-0
• 化学式: C₂₄H₂₇NO₄
• 分子量: 393.483
• InChiKey: MYCOAJZXTGFHDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2-叔丁氧基-2-氧代乙氧基)苯甲酸 、 3-N-(9-fluorenylmethoxycarbonyl)-amino-2-cyclohexylpropionic acid 、 3-羟基-4-甲基-2-硝基苯甲酸 、 Fmoc-Lys(Dde)-OH 生成 2-[3-[[(5S)-6-[(3-amino-2-cyclohexyl-3-oxopropyl)amino]-5-[(3-hydroxy-4-methyl-2-nitrobenzoyl)amino]-6-oxohexyl]carbamoyl]phenoxy]acetic acid
  参考文献：
  名称：

  Aminodeoxychorismate Synthase Inhibitors from One-Bead One-Compound Combinatorial Libraries:  “Staged” Inhibitor Design

  摘要：

  4-Amino-4-deoxychorismate synthase (ADCS) catalyzes the first step in the conversion of chorismate into p-aminobenzoate, which is incorporated into folic acid. We aim to discover compounds that inhibit ADCS and serve as leads for a new class of antimicrobial compounds. This report presents (1) synthesis of a mass-tag encoded library based on a "staged" design, (2) massively parallel fluorescence-based on-bead screening, (3) rapid structural identification of hits, and (4) full kinetic analysis of ADCS. All inhibitors are competitive against chorismate and Mg2+. The most potent ADCS inhibitor identified has a K-i of 360 mu M. We show that the combinatorial diversity elements add substantial binding affinity by interacting with residues outside of but proximal to the active site. The methods presented here constitute a paradigm for inhibitor discovery through active site targeting, enabled by rapid library synthesis, facile massively parallel screening, and straightforward hit identification.

  DOI：

  10.1021/jm0609869