1-氟-2-萘酸 | 574-97-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 1-氟-2-萘酸
• 英文名称: 1-fluoro-2-naphthoic acid
• 英文别名: 1-Fluoronaphthalene-2-carboxylic acid；1-fluoronaphthalene-2-carboxylic acid
• CAS: 574-97-0
• 化学式: C₁₁H₇FO₂
• 分子量: 190.174
• InChiKey: XKFQSLSAPMCGQS-UHFFFAOYSA-N

物化性质

• 熔点：
  193-194 °C
• 沸点：
  328.4±17.0 °C(Predicted)
• 密度：
  1.355±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 储存条件：
  存储在室温下

反应信息

• 作为反应物：
  描述：

  1-氟-2-萘酸 、 苯基溴化镁 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以80%的产率得到1-苯基萘-2-羧酸
  参考文献：
  名称：

  METHOD FOR PREPARING CHEMICAL COMPOUNDS OF INTEREST BY NUCLEOPHILIC AROMATIC SUBSTITUTION OF AROMATIC CARBOXYLIC ACID DERIVATIVES SUPPORTING AT LEAST ONE ELECTRO-ATTRACTIVE GROUP

  摘要：

  通过芳香亲核取代法制备羧酸衍生物的方法，其中羧酸衍生物具有单个羧基官能团，或其盐之一，该羧酸衍生物在羧基官能团的邻位具有一个离去基团，该离去基团优选为氟原子或氯原子或烷氧基，手性或非手性，优选为甲氧基，如果有的话，该羧酸衍生物未被电子亲合基团取代；与反应物MNu发生反应，其中M为金属，Nu为亲核试剂，手性或非手性，芳香亲核取代反应在无催化剂和无保护/去保护起始化合物的酸官能团的步骤的情况下进行。

  公开号：

  US20120316337A1
• 作为产物：
  描述：

  二氧化碳 、 1-氟萘 在 仲丁基锂 作用下， 以 四氢呋喃 、 环己烷 为溶剂， 反应 2.5h， 以73%的产率得到1-氟-2-萘酸
  参考文献：
  名称：

  萘甲酸的手性配体介导的亲核芳香取代：快速有效地获得轴向手性联芳基。

  摘要：

  通过亲核芳族取代的联芳基对映体富集的过渡无金属合成（S Ñ报道的萘甲酸的Ar）反应。用对映纯反式-1，2-二甲氧基环己烷可获得最好的对映体控制。该反应提供了对映富集的双萘，苯基萘和菲基萘的有效途径。

  DOI：

  10.1002/ejoc.202000317

文献信息

• [EN] NOVEL AGENTS TARGETING CYP51<br/>[FR] NOUVEAUX AGENTS CIBLANT CYP51
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2015048306A1

  公开（公告）日：2015-04-02

  The invention provides inhibitors of a sterol C14-demethylase, a new series of 4- aminopyridyl-based lead inhibitors targeting Trypanosoma cruzi CYP51 (TcCYP51) developed using structure-based drug design as well as structure -property relationship (SPR) analyses. The screening hit starting point, LP 10 (KD < 42 nM; EC50 of 0.65 μΜ), has been optimized to give the potential leads that have low nanomolar binding affinity to TcCYP51 and significant activity against T. cruzi amastigotes cultured in human myoblasts. Many of the optimized compounds have improved microsome stability, and most are selective against the T. cruzi CYP51 relative to human CYPs 1A2, 2D6 and 3A4 (<50% inhibition at 1 μΜ). A rationale for the improvement of microsome stability and selectivity of inhibitors against human metabolic CYP enzymes is presented. In addition, the binding mode of several compounds of the invention with the T. brucei CYP51 (TbCYP51) ortholog has been characterized by x-ray structure analysis. Orally active compounds and their cyclodextrin complexes have been shown to be effective against Chagas-infected mice.

  该发明提供了一种甾醇C14-去甲基酶的抑制剂，这是一种新系列基于4-氨基吡啶的首选抑制剂，通过基于结构的药物设计以及结构-性质关系（SPR）分析来瞄准Trypanosoma cruzi CYP51（TcCYP51）而开发的。筛选起始点LP 10（KD < 42 nM；EC50为0.65 μΜ）已经经过优化，产生了具有低纳摩尔级别结合亲和力和对在人类肌细胞培养的T. cruzi游离体的显著活性的潜在首选抑制剂。许多经过优化的化合物具有改善的微粒体稳定性，大多数相对于人类CYPs 1A2、2D6和3A4对T. cruzi CYP51具有选择性（在1 μΜ下<50%的抑制）。提出了改善微粒体稳定性和抑制剂对人类代谢CYP酶的选择性的理由。此外，通过X射线结构分析表征了该发明的几种化合物与T. brucei CYP51（TbCYP51）同源物的结合方式。口服活性化合物及其环糊精复合物已被证明对克氏病感染的小鼠有效。
• <i>ortho</i>-Lithium/Magnesium Carboxylate-Driven Aromatic Nucleophilic Substitution Reactions on Unprotected Naphthoic Acids
  作者：Regadia Aissaoui、Arnaud Nourry、Ariane Coquel、Thi Thanh Hà Dao、Aicha Derdour、Jean-Jacques Helesbeux、Olivier Duval、Anne-Sophie Castanet、Jacques Mortier

  DOI：10.1021/jo202017z

  日期：2012.1.6

  acids furnishing substituted naphthoic acids occurs in good to excellent yields upon reaction with alkyl/vinyl/aryl organolithium and Grignard reagents, in the absence of a metal catalyst without the need to protect the carboxyl (CO2H) group. This novel nucleophilic aromatic substitution is presumed to proceed via a precoordination of the organometallic with the substrate, followed by an addition/elimination

  在不需要金属催化剂的情况下，与烷基/乙烯基/芳基有机锂和格利雅试剂反应后，提供取代萘酸的1-萘甲酸和2-萘甲酸中的邻氟或甲氧基取代反应的收率非常好。保护羧基（CO 2 H）。据推测，该新的亲核芳族取代是通过有机金属与底物的预配位，然后添加/消除来进行的。
• Rational Development of 4-Aminopyridyl-Based Inhibitors Targeting Trypanosoma cruzi CYP51 as Anti-Chagas Agents
  作者：Jun Yong Choi、Claudia M. Calvet、Shamila S. Gunatilleke、Claudia Ruiz、Michael D. Cameron、James H. McKerrow、Larissa M. Podust、William R. Roush

  DOI：10.1021/jm401067s

  日期：2013.10.10

  A new series of 4-aminopyridyl-based lead inhibitors targeting Trypanosoma cruzi CYP51 (TcCYP51) has been developed using structure-based drug design as well as structure-property relationship (SPR) analyses. The screening hit starting point, LP10 (K-D <= 42 nM; EC50 = 0.65 mu M), has been optimized to give the potential leads 14t, 27i, 27q, 27r, and 27t, which have low-nanomolar binding affinity to TcCYR51 and significant activity against T. cruzi amastigotes cultured in human myoblasts (EC50 = 14-18 nM for 27i and 27r). Many of the optimized compounds have improved microsome stability, and most are selective against human CYPs 1A2, 2D6, and 3A4 (<50% inhibition at 1 mu M). A rationale for the improvement in microsome stability and selectivity of inhibitors against human metabolic CYP enzymes is presented. In addition, the binding mode of 14t with the Trypanosoma brucei CYP51 (TbCYP51) orthologue has been characterized by X-ray structure analysis.
• The Basicity Gradient-Driven Migration of Iodine: Conferring Regioflexibility on the Substitution of Fluoroarenes
  作者：Thierry Rausis、Manfred Schlosser

  DOI：10.1002/1099-0690(200210)2002:19<3351::aid-ejoc3351>3.0.co;2-i

  日期：2002.10
• Synthesis of monomeric and oligomeric naphtho- and biaryl-fused 1,8-diaza-14-crown-4 macrocycles
  作者：Arthur G. Schultz、Zihong Guo

  DOI：10.1016/0040-4039(94)02345-c

  日期：1995.1

  Efficient syntheses of naphtho- and biaryl-fused 1,8-diaza-14-crown-4 macrocycles 4a, 4b, 7a, and 7b and related oligomeric systems 11 and 15 are described, An X-ray structure determination for the N,N-dicyanomethyl substituted macrocycle 8 is reported.