3-imidazol-1-yl-3-[4-(6-methoxynaphthalen-2-ylamino)phenyl]-2,2-dimethylpropionic acid methyl ester | 1202273-79-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-imidazol-1-yl-3-[4-(6-methoxynaphthalen-2-ylamino)phenyl]-2,2-dimethylpropionic acid methyl ester
• 英文别名: 3-Imidazol-1-yl-3-[4-(6-methoxy-naphthalen-2-ylamino)-phenyl]-2,2-dimethyl-propionic acid methyl ester；methyl 3-imidazol-1-yl-3-[4-[(6-methoxynaphthalen-2-yl)amino]phenyl]-2,2-dimethylpropanoate
• CAS: 1202273-79-7
• 化学式: C₂₆H₂₇N₃O₃
• 分子量: 429.519
• InChiKey: MUEVWLXTTJDOEB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  65.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-imidazol-1-yl-3-[4-(6-methoxynaphthalen-2-ylamino)phenyl]-2,2-dimethylpropionic acid methyl ester 在 三氯化硼 、 四丁基碘化铵 作用下， 以 二氯甲烷 为溶剂， 以49%的产率得到3-[4-(6-hydroxy-naphthalen-2-ylamino)-phenyl]-3-imidazol-1-yl-2,2-dimethyl-propionic acid methyl ester
  参考文献：
  名称：

  维甲酸4-羟化酶（CYP26）的小分子抑制剂：咪唑3-（4-（芳基-2-基氨基）苯基）丙酸甲酯的合成及生物评价

  摘要：

  描述了新型咪唑甲基3-（4-（芳基-2-基氨基）苯基）丙酸酯在MCF-7 CYP26A1微粒体测定中的合成和强抑制活性。CYP26A1 mRNA的诱导用于评估化合物增强类视黄醇反应性神经母细胞瘤细胞系中全反式视黄酸（ATRA）的生物学效应的能力。最有希望的抑制剂3-咪唑-1-基-2-甲基-3- [4-（萘-2-基氨基）-苯基]-丙酸甲酯（20），IC 50为3 nM（相比用利阿罗唑IC 50 540纳米和R116010 IC 50为10nM）中的溶液用于CYP选择性使用CYP酶，致突变性（艾姆斯画面），和肝稳定性的面板进一步评估。

  DOI：

  10.1021/jm101583w
• 作为产物：
  描述：

  6-甲氧基萘-2-硼酸 在 吡啶 、 copper diacetate 、 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 48.0h， 生成 3-imidazol-1-yl-3-[4-(6-methoxynaphthalen-2-ylamino)phenyl]-2,2-dimethylpropionic acid methyl ester
  参考文献：
  名称：

  [EN] CYP26 INHIBITORS
  [FR] INHIBITEURS DE CYP26

  摘要：

  公式（I）的化合物，其中X选择自O、S、NH或CH2；Rd和Rp是可选的萘基取代物；RHet是咪唑基、三唑基或吡啶基；Rc是C1-4烷基，通过选择的基团取代，包括：羟基、氨基、酰胺基、羧基、C1-7烷基酯、C5-7芳基-C1-2烷基酯、磺胺基、亚砜胺基、羟胺基和四唑基。

  公开号：

  WO2009153566A1

文献信息

• Synthesis and Biological Evaluation of 3-(1<i>H</i>-Imidazol- and Triazol-1-yl)-2,2-dimethyl-3-[4-(naphthalen-2-ylamino)phenyl]propyl Derivatives as Small Molecule Inhibitors of Retinoic Acid 4-Hydroxylase (CYP26)
  作者：Mohamed S. Gomaa、Caroline E. Bridgens、Gareth J. Veal、Christopher P. F. Redfern、Andrea Brancale、Jane L. Armstrong、Claire Simons

  DOI：10.1021/jm200695m

  日期：2011.10.13

  len-2-ylamino)-phenyl]-3-[1,2,4]triazol-1-yl-propionic acid methyl ester (17) (IC50 = 0.35 nM as compared with liarozole IC50 = 540 nM and R116010 IC50 = 10 nM) was evaluated for CYP selectivity and hepatic stability. Compounds with CYP26 inhibitory IC50 values ≤50 nM enhanced the biological activity of exogenous ATRA, as evidenced by a 3.7–5.8-fold increase in CYP26A1 mRNA in SH-SY5Y neuroblastoma

  新型3-（1 H-咪唑-和三唑-1-基）-2,2-二甲基-3-（4-（萘-2-基氨基）苯基）丙基衍生物的合成及其强抑制活性描述了7种CYP26A1微粒体测定法。这项研究的重点是修饰血红素结合唑基和柔性C3链对抑制活性和选择性的影响。最有希望的抑制剂2,2-二甲基-3- [4-（萘-2-基氨基）-苯基] -3- [1,2,4]三唑-1-基-丙酸甲酯（17）（IC与利拉唑IC 50 = 540 nM和R116010 IC 50 = 10 nM相比，评估了50 = 0.35 nM的CYP选择性和肝稳定性。具有CYP26抑制IC 50的化合物值≤50nM增强外源性ATRA的生物活性，与单独使用ATRA相比，SH-SY5Y神经母细胞瘤细胞中CYP26A1 mRNA的增加3.7-5.8倍证明了这一点。所有化合物均显示出与R116010相当或更好的活性，且诱导作用与CYP26抑制数据密切相关。这些研究突
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