2045-39-8

Usage

InChI:InChI=1/C8H8FNO2/c1-5(11)10-6-2-3-8(12)7(9)4-6/h2-4,12H,1H3,(H,10,11)

Upstream product

• 366-99-4 3-fluoro-4-methoxyaniline 
• 446-31-1 2-fluoro-4-aminobenzoic acid 
• 72-89-9 acetylcoenzyme A 
• 402-67-5 3-fluoro-1-nitrobenzene 
• 2369-20-2 N-(3-fluorophenyl)hydroxylamine 
• 399-96-2 4-amino-2-fluorophenol 
• 108-24-7 acetic anhydride 
• 123-54-6 acetylacetone 
• 403-19-0 2-fluoro-4-nitrophenol 
• 452-15-3 N-(3-fluoro-4-methoxyphenyl)acetamide 

Downstream Products

• 868733-51-1 N-(4-(2-chloropyridin-4-yloxy)-3-fluorophenyl)acetamide 
• 1025986-25-7 4-Amino-2-diethylaminomethyl-6-fluoro-phenol 
• 155020-43-2 3-<(diethylamino)methyl>-5-fluoro-4-hydroxyacetanilide 

Relevant academic research and scientific papers

De novo biosynthesis and whole-cell catalytic production of paracetamol on a gram scale in Escherichia coli

The synthetic drug paracetamol is one of the most commonly used analgesic, antipyretic agents around the world. Global massive demand promoted its synthesis in large quantities. Chemical synthesis is the main approach for paracetamol production. However, the reaction process contributes toward environmental pollution, and the reaction conditions are harsh. Herein, we reported the construction of the paracetamol de novo biosynthetic pathway in Escherichia coli. Five enzymes from different microbial sources were heterologously expressed into E. coli to construct the APAP (1) producing strain PA1. Through protein engineering of ABH (4-aminobenzoate hydroxylase) and PANAT (arylamine N-acetyltransferase), enhancement of the host cell resistance to the substrate or final product, and utilizing synthetic protein scaffolds to optimize the metabolic flux, the engineered strain could produce 942.5 mg L-1 (6.24 mM) paracetamol in a fed-batch 5 L fermenter directly from glucose or glycerol, which circumvents the fossil fuel resource use. Moreover, we established a whole-cell cascade biocatalytic synthesis way to paracetamol and analogues. Using p-aminobenzoate as the substrate, 4.2 g L-1 (27.7 mM) paracetamol can be formed after 9 h (95% conversion rate). After metabolic engineering, enzyme molecular modification, and other optimizations, we created the biotransformation strategy to manufacture paracetamol on a gram scale. This study provides a promising green and efficient alternative to the traditional chemical manufacturing method.

Redox-Neutral Selenium-Catalysed Isomerisation of para-Hydroxamic Acids into para-Aminophenols

A selenium-catalysed para-hydroxylation of N-aryl-hydroxamic acids is reported. Mechanistically, the reaction comprises an N?O bond cleavage and consecutive selenium-induced [2,3]-rearrangement to deliver para-hydroxyaniline derivatives. The mechanism is studied through both 18O-crossover experiments as well as quantum chemical calculations. This redox-neutral transformation provides an unconventional synthetic approach to para-aminophenols.

Substituted pyridazinone compound and application thereof

The invention provides a substituted pyridazinone compound and application thereof. The substituted pyridazinone compound is a compound shown in a general formula I, or a pharmaceutically acceptable salt, a prodrug, a hydrate or a solvent compound, a poly

PHENOXY-PYRIDYL-PYRIMIDINE COMPOUNDS AND METHODS OF USE

Described herein are phenoxy-pyridyl -pyrimidine compounds with inositol requiring enzyme 1 (IRE1) modulation activity or function having the Formula I structure or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I compounds, as well as methods of using such IRE1 modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.

H2O2-mediated oxidative formation of amides from aromatic amines and 1,3-diketones as acylation agents via C-C bond cleavage at room temperature in water under metal-free conditions

1,3-Diketones, as novel acylation agents, reacted with aromatic amines promoted by commercially available H2O2 (30% aq.) as the sole oxidant at room temperature under metal-free conditions in water, leading to a novel and rapid amide bond formation strategy. The reported method is high-yielding, simple and mild, and is the first example of the use of 1,3-diketones as acylation agents via C-C bond cleavage.

Monocyclic heterocycles as kinase inhibitors

The present invention is directed to compounds having the formula and methods for using them for the treatment of cancer.

The Effect of Fluorine Substitution on the Metabolism and Antimalarial Activity of Amodiaquine

Amodiaquine (AQ) (2) is a 4-aminoquinoline antimalarial which causes adverse side effects such as agranulocytosis and liver damage.The observed drug toxicity is believed to be related to the formation of an electrophilic metabolite, amodiaquine imine (AQQI), which can bind to cellular macro-molecules and initiate hypersensitivity reactions. 5'-Fluoroamodiaquine (5'-FAQ, 3), 5',6'-difluoroamodiaquine (5',6'-DIFAQ, 4), 2',6'-difluoroamodiaquine (2',6'-DIFAQ, 5), 2',5',6'-trifluoroamodiaquine (2',5',6'-TRIFAQ, 6) and 4'-dehydroxy-4'-fluoroamodiaquine (4'-deOH-4'-FAQ, 7) have been synthesized to assess the effect of fluorine substitution on the oxidation potential, metabolism, and in vitro antimalarial activity of amodiaquine.The oxidation potentials were measured by cyclic voltammetry, and it was observed that substitution at the 2',6'- and 4'-positions (2',6'-DIFAQ and 4'-deOH'4'-FAQ) produced analogues with significantly higher oxidation potentials than the parent drug.Fluorine substitution at the 2',6'-positions and 4'-position also produced analogues that were more resistant to bioactivation.Thus 2',6'-DIFAQ and 4'-deOH-4'-FAQ produced thioether conjugates corresponding to 2.17percent (SD: +/-0.27percent) and 0percent of the dose compared with 11.87percent (SD: +/-1.31percent) of the dose for amodiaquine.In general the fluorinated analogues had similar in vitro antimalarial activity to amodiaquine against the chloroquine resistant K1 strain of Plasmodium falciparum and the chloroquine sensitive T9-96 strain of P. falciparum with the notable exception of 2',5',6'-TRIFAQ (6).The data presented indicate that fluorine substitution at the 2',6'-positions and replacement of the 4'-hydroxyl of amodiaquine with fluorine produces analogues ( 5 and 7) that maintain antimalarial efficacy in vitro and are more resistant to oxidation and hence less likely to form toxic quinone imine metabolites.

The effect of fluorine substitution on the physicochemical properties and the analgesic activity of paracetamol

The physicochemical properties and analgesic action of six fluorinated analogues of 4-hydroxyacetanilide (paracetamol) have been investigated. Fluorine substitution adjacent to the hydroxyl group increased lipophilicity and oxidation potential whilst substitution adjacent to the amide had little effect on lipophilicity but led to a greater increase in oxidation potential. Lack of coplanarity and conjugation of the amide group and aromatic ring was also apparent with the analogues that had fluorine in the 2 and 6 positions. Introduction of fluorine into the amide group of paracetamol increased the lipophilicity 4-fold and also increased the oxidation potential of paracetamol. ED50 values for analgesic activity in the phenylquinone-induced abdominal constriction test on male Swiss White mice showed that ring substitution by fluorine reduced activity, especially at the 2,6-positions. Introduction of fluorine into the amide group enhanced activity significantly. Correlation of the analgesic activity with the physicochemical properties indicated that conjugation (and planarity) of the amide group with the aromatic ring is essential for activity and that ease of oxidation may also be an important factor.