N-(acetylphenyl)adamantane-1-carboxamide | 121768-33-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(acetylphenyl)adamantane-1-carboxamide
• 英文别名: N-(4-acetylphenyl)adamantane-1-carboxamide
• CAS: 121768-33-0
• 化学式: C₁₉H₂₃NO₂
• mdl: MFCD01825679
• 分子量: 297.397
• InChiKey: ZTMRQHBDPMLFHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(对羟基苯基)-2-硫脲 、 N-(acetylphenyl)adamantane-1-carboxamide 在 溴 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 3.0h， 以32%的产率得到N-(4-{2-[(4-hydrophenyl)amino]-1,3-thiazol-4-yl}phenyl)adamantane-1-carboxamide
  参考文献：
  名称：

  Exploring the Chemical Space of Multitarget Ligands Using Aligned Self-Organizing Maps

  摘要：

  Design of multitarget drugs and polypharmacological compounds has become popular during the past decade. However, the main approach to design such compounds is to link two selective ligands via a flexible linker. Although such, chimeric ligands often have reasonable potency in vitro, the in vivo efficacy is low due to high molecular weight, low ligand efficiency, and poor pharmacokinetic profile. We developed an unprecedented in silico approach for fragment-based design of multitarget ligands. It relies on superposition of the chemical spaces related to the affinity on single targets represented by self-organizing maps. We used this approach for screening of molecular fragments, which bind to the enzymes 5-lipoxygenase (5-LO) and soluble epoxide hydrolase (sEH). Using STD-NMR and activity-based assays, we were able to identify fragments binding to both targets. Furthermore, we were able to expand one of the fragments to a potent dual inhibitor bearing a reasonable molecular weight (MW = 446) and high affinity to both targets (IC50 of 0.03 mu M toward 5-LO and 0.17 mu M toward sEH).

  DOI：

  10.1021/ml4002562
• 作为产物：
  描述：

  金刚烷酰氯 、 4-氨基苯乙酮 在 吡啶 作用下， 以 1,4-二氧六环 为溶剂， 以75%的产率得到N-(acetylphenyl)adamantane-1-carboxamide
  参考文献：
  名称：

  Exploring the Chemical Space of Multitarget Ligands Using Aligned Self-Organizing Maps

  摘要：

  Design of multitarget drugs and polypharmacological compounds has become popular during the past decade. However, the main approach to design such compounds is to link two selective ligands via a flexible linker. Although such, chimeric ligands often have reasonable potency in vitro, the in vivo efficacy is low due to high molecular weight, low ligand efficiency, and poor pharmacokinetic profile. We developed an unprecedented in silico approach for fragment-based design of multitarget ligands. It relies on superposition of the chemical spaces related to the affinity on single targets represented by self-organizing maps. We used this approach for screening of molecular fragments, which bind to the enzymes 5-lipoxygenase (5-LO) and soluble epoxide hydrolase (sEH). Using STD-NMR and activity-based assays, we were able to identify fragments binding to both targets. Furthermore, we were able to expand one of the fragments to a potent dual inhibitor bearing a reasonable molecular weight (MW = 446) and high affinity to both targets (IC50 of 0.03 mu M toward 5-LO and 0.17 mu M toward sEH).

  DOI：

  10.1021/ml4002562

文献信息

• SKWARSKI, DIONIZY;MALISZEWSKA, HALINA, ACTA POL. PHARM., 45,(1988) N, C. 301-305
  作者：SKWARSKI, DIONIZY、MALISZEWSKA, HALINA

  DOI：——

  日期：——
• Exploring the Chemical Space of Multitarget Ligands Using Aligned Self-Organizing Maps
  作者：Janosch Achenbach、Franca-Maria Klingler、René Blöcher、Daniel Moser、Ann-Kathrin Häfner、Carmen B. Rödl、Simon Kretschmer、Björn Krüger、Frank Löhr、Holger Stark、Bettina Hofmann、Dieter Steinhilber、Ewgenij Proschak

  DOI：10.1021/ml4002562

  日期：2013.12.12

  Design of multitarget drugs and polypharmacological compounds has become popular during the past decade. However, the main approach to design such compounds is to link two selective ligands via a flexible linker. Although such, chimeric ligands often have reasonable potency in vitro, the in vivo efficacy is low due to high molecular weight, low ligand efficiency, and poor pharmacokinetic profile. We developed an unprecedented in silico approach for fragment-based design of multitarget ligands. It relies on superposition of the chemical spaces related to the affinity on single targets represented by self-organizing maps. We used this approach for screening of molecular fragments, which bind to the enzymes 5-lipoxygenase (5-LO) and soluble epoxide hydrolase (sEH). Using STD-NMR and activity-based assays, we were able to identify fragments binding to both targets. Furthermore, we were able to expand one of the fragments to a potent dual inhibitor bearing a reasonable molecular weight (MW = 446) and high affinity to both targets (IC50 of 0.03 mu M toward 5-LO and 0.17 mu M toward sEH).