3,4-dichloro-N-(4-fluorobenzyl)aniline

• 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: 3,4-dichloro-N-(4-fluorobenzyl)aniline
• 英文别名: 3,4-dichloro-N-[(4-fluorophenyl)methyl]aniline
• 化学式: C₁₃H₁₀Cl₂FN
• mdl: MFCD03210771
• 分子量: 270.134
• InChiKey: IXMMFUMVGXKTGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.076
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,4-dichloro-N-(4-fluorobenzyl)aniline 在 盐酸 、 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 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 3-((3,4-dichlorophenyl)(4-fluorobenzyl)amino)-N-(4-methoxyphenyl)propanamide
  参考文献：
  名称：

  抑制胆固醇酯转移蛋白（CETP）的新型β-丙酰胺的合成

  摘要：

  摘要合成了一系列新的β-丙酰胺衍生物作为胆固醇酯转移蛋白（CETP）抑制剂。以前，人们观察到H3（IC 50 2μmol/ L）可以适度抑制CETP（Xie et al。，2016）。基于H3的结构修饰导致成功的CETP抑制剂的发现，称为1-甲基-4-芳基吡唑。使用类似的方法，化合物Q08被鉴定为高效CETP抑制剂，体外IC 50为490 nmol / L。

  DOI：

  10.1016/j.cclet.2016.10.016
• 作为产物：
  描述：

  (3,4-Dichloro-phenyl)-(4-fluoro-benzylidene)-amine 在 sodium tetrahydroborate 作用下， 生成 3,4-dichloro-N-(4-fluorobenzyl)aniline
  参考文献：
  名称：

  抑制胆固醇酯转移蛋白（CETP）的新型β-丙酰胺的合成

  摘要：

  摘要合成了一系列新的β-丙酰胺衍生物作为胆固醇酯转移蛋白（CETP）抑制剂。以前，人们观察到H3（IC 50 2μmol/ L）可以适度抑制CETP（Xie et al。，2016）。基于H3的结构修饰导致成功的CETP抑制剂的发现，称为1-甲基-4-芳基吡唑。使用类似的方法，化合物Q08被鉴定为高效CETP抑制剂，体外IC 50为490 nmol / L。

  DOI：

  10.1016/j.cclet.2016.10.016

文献信息

• Sulfonic acid functionalized covalent organic frameworks as efficient catalyst for the one-pot tandem reactions
  作者：Kai Gong、Cunhao Li、Daquan Zhang、Huilin Lu、Yunyun Wang、Haoran Li、Huimin Zhang

  DOI：10.1016/j.mcat.2022.112139

  日期：2022.2

  the cyclotrimerization reaction of acetyls, which was used as a pre-established network to introduce propyl sulfonic acid through post-synthetic modification strategy, for the fabrication of SO3H-COF with graphene-like multilayer structure. SO3H-COF was employed as an effective heterogeneous catalyst for the synthesis of benzimidazoles, the synthesis of benzodiazepines and one-pot reductive amination

  通过乙酰基的环三聚反应预先设计和合成了一种含有羟基的共价有机骨架（HO-COF），该骨架被用作预先建立的网络，通过合成后修饰策略引入丙基磺酸，用于制备 SO具有类石墨烯多层结构的3 H-COF。SO 3 H-COF 作为一种有效的多相催化剂用于苯并咪唑的合成、苯二氮卓类的合成和羰基化合物的一锅还原胺化。结果表明，所开发的方案具有活性高、底物范围广、反应时间短、收率高等优点。SO 3的独特结构H-COF具有优异的催化性能、良好的稳定性和循环性能。
• HIV integrase inhibitors
  申请人：——

  公开号：US20030181490A1

  公开（公告）日：2003-09-25

  The present invention relates to the inhibition of HIV integrase, and to the treatment of AIDS or ARC by administering compounds of the formula 1 wherein R 1 is C 1 -C 4 alkyl, carbocyclic radical, heterocyclic radical, aryl-C 1 -C 2 alkylene, aryloxy-C 1 -C 2 alkylene, alkoxy-CC(O)—, wherein R 1 is optionally substituted from 1-3 times with halo, C 1 -C 2 alkyl or C 1 -C 2 alkoxy, or R 1 is H; R 2 is H or C 1 -C 4 alkyl; R 3 is H, C 1 -C 4 alkyl or phenyl-C 0 -C 2 alkylene which is optionally substituted with 1-3 R 5 ; R 4a is carbocylic radical, heterocyclic radical, aryloxy, aryl-C 1 -C 4 alkylene, aryl-cyclopropylene, aryl-NHC(O)—, wherein R 4a is optionally substituted with 1-3 R 5 ; and wherein each R 5 is independently selected from H, halo, C 1 -C 4 alkyl, C 1 -C 4 alkenyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, R 6 -phenyl, R 6 -phenoxy, R 6 -benzyl, R 6 -benzyloxy, NH 2 C (O)—, alkyl-NHC(O)—, wherein R 6 is H, halo; Z is a bond or a substituted or unsubstituted C 1 -C 4 alkylene group; and B 2 is 2

  本发明涉及抑制HIV整合酶的化合物，并通过给予式1中的化合物治疗艾滋病或ARC，其中R1为C1-C4烷基，碳环基，杂环基，芳基-C1-C2烷基，芳氧基-C1-C2烷基，烷氧基-CC（O）-，其中R1可以用卤素，C1-C2烷基或C1-C2烷氧基从1-3次取代，或R1为H；R2为H或C1-C4烷基；R3为H，C1-C4烷基或苯基-C0-C2烷基，该苯基-C0-C2烷基可以选择性地用1-3个R5取代；R4a为碳环基，杂环基，芳氧基，芳基-C1-C4烷基，芳基环丙基，芳基-NHC（O）-，其中R4a可以选择性地用1-3个R5取代；每个R5都是独立选择的H，卤素，C1-C4烷基，C1-C4烯基，C1-C4卤代烷基，C1-C4烷氧基，R6-苯基，R6-苯氧基，R6-苄基，R6-苄氧基，NH2C（O）-，烷基-NHC（O）-，其中R6为H，卤素；Z为键或取代或未取代的C1-C4烷基；B2为2。
• Discovery of novel N,N-3-phenyl-3-benzylaminopropionanilides as potent inhibitors of cholesteryl ester transfer protein in vivo
  作者：Honglei Xie、Yiqun Li、Changlin Bai、Ruifeng Wang、Chunchi Liu、Chenzhou Hao、Bin Lin、Maosheng Cheng、Dongmei Zhao

  DOI：10.1016/j.bmc.2016.03.002

  日期：2016.4

  Epidemiological studies have identified that the risk of cardiovascular events increases due to the decreased levels of high density lipoprotein-cholesterol and the elevated levels of low density lipoprotein-cholesterol. Herein, we report a novel series of N,N-3-phenyl-3-benzylaminopropionanilide derivatives, which were identified as potent cholesteryl ester transfer protein (CETP) inhibitor. The initial lead compound L10 (IC50 8.06 mu M) was found by pharmacophore-based virtual screening (Dong-Mei Zhao et al., Chin. Chem. Lett. 2014, 25, 299). After systematic structure variation and biological testing against CETP, two different series were identified as scaffolds for potent CETP inhibitors. One is N,N-3-phenyl-3-benzylaminopropanamide derivatives, which were investigated in our previous paper (Bioorg. Med. Chem. 2015, doi: http://dx.doi.org/10.1016/j.bmc.2015.12.010). The most potent compound HL16 in that series has the IC50 of 0.69 mu M. The other series is N, N-3-phenyl-3-benzylaminopropionanilide derivatives, which was investigated in current study. Further optimization of the structure-activity relationship (SAR) resulted in H16 (IC50 0.15 mu M), which was discovered as a potent CETP inhibitor in vitro by BODIPY-CE fluorescence assay. In addition, the results of pharmacodynamics studies showed that H16 exhibited both favorable HDL-C enhancement and LDL-C reduction in vivo by hamster. It also has an excellent stability in rat liver microsomal. (C) 2016 Elsevier Ltd. All rights reserved.
• Binding Mode Characterization and Early <i>in Vivo</i> Evaluation of Fragment-Like Thiols as Inhibitors of the Virulence Factor LasB from <i>Pseudomonas aeruginosa</i>
  作者：Andreas M. Kany、Asfandyar Sikandar、Jörg Haupenthal、Samir Yahiaoui、Christine K. Maurer、Ewgenij Proschak、Jesko Köhnke、Rolf W. Hartmann

  DOI：10.1021/acsinfecdis.8b00010

  日期：2018.6.8

  The increasing emergence of antibiotic resistance necessitates the development of anti-infectives with novel modes of action. Targeting bacterial virulence is considered a promising approach to develop novel antibiotics with reduced selection pressure. The extracellular collagenase elastase (LasB) plays a pivotal role in the infection process of Pseudomonas aeruginosa and therefore represents an attractive antivirulence target. Mercaptoacetamide-based thiols have been reported to inhibit LasB as well as collagenases from MMPs clostridia and bacillus species. The present work provides an insight into the structure activity relationship (SAR) of these fragment-like LasB inhibitors, demonstrating an inverse activity profile compared to similar inhibitors of clostridial collagenase H (CoIH). An X-ray cocrystal structure is presented, revealing distinct binding of two compounds to the active site of LasB, which unexpectedly maintains an open conformation. We further demonstrate in vivo efficacy in a Galleria mellonella infection model and high selectivity of the LasB inhibitors toward human matrix metalloproteinases (MMPs).
• US6803378B2
  申请人：——

  公开号：US6803378B2

  公开（公告）日：2004-10-12