5-fluoro-N,2-dimethylbenzamide | 1332325-17-3

• 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: 5-fluoro-N,2-dimethylbenzamide
• CAS: 1332325-17-3
• 化学式: C₉H₁₀FNO
• mdl: MFCD19596596
• 分子量: 167.183
• InChiKey: MJYBYHBEAJWYCL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-fluoro-N,2-dimethylbenzamide 在 N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 偶氮二异丁腈 、 三苯基膦 作用下， 以 四氢呋喃 、 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 2-(aminomethyl)-5-fluoro-N-methylbenzamide
  参考文献：
  名称：

  Design of HIV-1 integrase inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75: A scaffold hopping approach using salicylate and catechol groups

  摘要：

  HIV-1 integrase (IN) is a validated therapeutic target for antiviral drug design. However, the emergence of viral strains resistant to clinically studied IN inhibitors demands the discovery of novel inhibitors that are structurally as well mechanistically different. Herein, we describe the design and discovery of novel IN inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75, which is essential for the HIV-1 integration as an IN cofactor. By merging the pharmacophores of salicylate and catechol, the 2,3-dihydroxybenzamide (5a) was identified as a new scaffold to inhibit the strand transfer reaction efficiently. Further structural modifications on the 2,3-dihydroxybenzamide scaffold revealed that the heteroaromatic functionality attached on the carboxamide portion and the piperidin-1-ylsulfonyl substituted at the phenyl ring are beneficial for the activity, resulting in a low micromolar IN inhibitor (5p, IC(50) = 5 mu M) with more than 40-fold selectivity for the strand transfer over the 3'-processing reaction. More significantly, this active scaffold remarkably inhibited the interaction between IN and LEDGF/p75 cofactor. The prototype example, N-(cyclohexylmethyl)-2,3-dihydroxy-5-(piperidin-1-ylsulfonyl) benzamide (5u) inhibited the IN-LEDGF/p75 interaction with an IC(50) value of 8 mu M. Using molecular modeling, the mechanism of action was hypothesized to involve the chelation of the divalent metal ions inside the IN active site. Furthermore, the inhibitor of IN-LEDGF/p75 interaction was properly bound to the LEDGF/p75 binding site on IN. This work provides a new and efficient approach to evolve novel HIV-1 IN inhibitors from rational integration and optimization of previously reported inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.058
• 作为产物：
  描述：

  5-氟-2-甲基苯甲酸 、 甲胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 6.5h， 以82%的产率得到5-fluoro-N,2-dimethylbenzamide
  参考文献：
  名称：

  Design of HIV-1 integrase inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75: A scaffold hopping approach using salicylate and catechol groups

  摘要：

  HIV-1 integrase (IN) is a validated therapeutic target for antiviral drug design. However, the emergence of viral strains resistant to clinically studied IN inhibitors demands the discovery of novel inhibitors that are structurally as well mechanistically different. Herein, we describe the design and discovery of novel IN inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75, which is essential for the HIV-1 integration as an IN cofactor. By merging the pharmacophores of salicylate and catechol, the 2,3-dihydroxybenzamide (5a) was identified as a new scaffold to inhibit the strand transfer reaction efficiently. Further structural modifications on the 2,3-dihydroxybenzamide scaffold revealed that the heteroaromatic functionality attached on the carboxamide portion and the piperidin-1-ylsulfonyl substituted at the phenyl ring are beneficial for the activity, resulting in a low micromolar IN inhibitor (5p, IC(50) = 5 mu M) with more than 40-fold selectivity for the strand transfer over the 3'-processing reaction. More significantly, this active scaffold remarkably inhibited the interaction between IN and LEDGF/p75 cofactor. The prototype example, N-(cyclohexylmethyl)-2,3-dihydroxy-5-(piperidin-1-ylsulfonyl) benzamide (5u) inhibited the IN-LEDGF/p75 interaction with an IC(50) value of 8 mu M. Using molecular modeling, the mechanism of action was hypothesized to involve the chelation of the divalent metal ions inside the IN active site. Furthermore, the inhibitor of IN-LEDGF/p75 interaction was properly bound to the LEDGF/p75 binding site on IN. This work provides a new and efficient approach to evolve novel HIV-1 IN inhibitors from rational integration and optimization of previously reported inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.058

文献信息

• [EN] NEW COMPOUNDS INHIBITORS OF THE YAP/TAZ-TEAD INTERACTION AND THEIR USE IN THE TREATMENT OF MALIGNANT MESOTHELIOMA<br/>[FR] NOUVEAUX COMPOSÉS INHIBITEURS DE L'INTERACTION YAP/TAZ-TEAD ET LEUR UTILISATION DANS LE TRAITEMENT DU MÉSOTHÉLIOME MALIN
  申请人：INVENTIVA

  公开号：WO2017064277A1

  公开（公告）日：2017-04-20

  The invention relates to compounds of formula (I) wherein R1, R2, R3, R4, R5 and R6 are as defined in the description. The compounds of formula (I) are inhibitors of the YAP/TAZ-TEAD interaction.

  该发明涉及公式（I）中的化合物，其中R1、R2、R3、R4、R5和R6如描述中所定义。公式（I）中的化合物是YAP/TAZ-TEAD相互作用的抑制剂。
• US3956391A
  申请人：——

  公开号：US3956391A

  公开（公告）日：1976-05-11
• US4107311A
  申请人：——

  公开号：US4107311A

  公开（公告）日：1978-08-15