860004-31-5

Upstream product

• 402-45-9 4-hydroxybenzotrifluoride 
• 1194-02-1 4-fluorobenzonitrile 
• 41571-86-2 1-trifluoromethyl-4-trimethylsilyloxybenzene 
• 3058-39-7 4-iodobenzonitrile 
• 98-56-6 4-chlorobenzotrifluoride 
• 128796-39-4 4-trifluoromethylphenylboronic acid 
• 767-00-0 4-cyanophenol 

Downstream Products

• 1087782-00-0 (Z)-N′-hydroxy-4-(4-(trifluoromethyl)phenoxy)benzimidamide 
• 1136832-67-1 5-(4-fluorophenyl)-3-(4-(4-(trifluoromethyl)phenoxy)-phenyl)-1,2,4-oxadiazole 
• 1567711-31-2 5-(4-(tert-butyldimethylsilyloxy)phenyl)-3-(4-(4-(trifluoromethyl)phenoxy)-phenyl)-1,2,4-oxadiazole 
• 1138697-97-8 (Z)-4-(4-(trifluoromethyl)phenoxy)-O-(4-(4-fluorobenzoyl)benzamidoxime) 
• 1136832-80-8 4-(3-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazol-5-yl)aniline 
• 1136832-79-5 3-(4-(4-(trifluoromethyl)phenoxy)phenyl)-5-(4-nitrophenyl-1,2,4-oxadiazole) 
• 1136832-72-8 4-(3-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazol-5-yl)phenol 

Relevant academic research and scientific papers

Structure-Activity Relationship Studies of Tolfenpyrad Reveal Subnanomolar Inhibitors of Haemonchus contortus Development

Recently, we have discovered that the registered pesticide, tolfenpyrad, unexpectedly and potently inhibits the development of the L4 larval stage of the parasitic nematode Haemonchus contortus with an IC50 value of 0.03 μM while displaying good selectivity, with an IC50 of 37.9 μM for cytotoxicity. As a promising molecular template for medicinal chemistry optimization, we undertook anthelmintic structure-activity relationships for this chemical. Modifications of the left-hand side (LHS), right-hand side (RHS), and middle section of the scaffold were explored to produce a set of 57 analogues. Analogues 25, 29, and 33 were shown to be the most potent compounds of the series, with IC50 values at a subnanomolar level of potency against the chemotherapeutically relevant fourth larval (L4) stage of H. contortus. Selected compounds from the series also showed promising activity against a panel of other different parasitic nematodes, such as hookworms and whipworms.

Probing the Azaaurone Scaffold against the Hepatic and Erythrocytic Stages of Malaria Parasites

The potential of azaaurones as dual-stage antimalarial agents was investigated by assessing the effect of a small library of azaaurones on the inhibition of liver and intraerythrocytic lifecycle stages of the malaria parasite. The whole series was screened against the blood stage of a chloroquine-resistant Plasmodium falciparum strain and the liver stage of P. berghei, yielding compounds with dual-stage activity and sub-micromolar potency against erythrocytic parasites. Studies with genetically modified parasites, using a phenotypic assay based on the P. falciparum Dd2-ScDHODH line, which expresses yeast dihydroorotate dehydrogenase (DHODH), showed that one of the azaaurone derivatives has the potential to inhibit the parasite mitochondrial electron-transport chain. The global urgency in finding new therapies for malaria, especially against the underexplored liver stage, associated with chemical tractability of azaaurones, warrants further development of this chemotype. Overall, these results emphasize the azaaurone chemotype as a promising scaffold for dual-stage antimalarials.

Copper mediated formation of carbon-heteroatom bonds using organoboron reagents and ultrasound

This report summarizes research efforts focused on copper acetate mediated reactions to form new carbon-heteroatom bonds using organoboron reagents under ultrasound irradiation. The method involves the application of ultrasound irradiation to the Chan-Evans-Lam reaction to achieve O-arylation of phenols, N-arylation of anilines and indoles, and S-arylation of thiols. Ultrasound irradiation was found to decrease reaction times from 72 hours to 4 hours while improving the product yields an average of 20%.1 Representative C-O, C-N, and C-S coupling reactions were successfully scaled-up from the milligram to gram levels while maintaining good product yields offering potential applications in industrial processes.

Structure-activity relationship for the oxadiazole class of antibiotics

The structure-activity relationship (SAR) for the newly discovered oxadiazole class of antibiotics is described with evaluation of 120 derivatives of the lead structure. This class of antibiotics was discovered by in silico docking and scoring against the crystal structure of a penicillin-binding protein. They impair cell-wall biosynthesis and exhibit activities against the Gram-positive bacterium Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant and linezolid-resistant S. aureus. 5-(1H-Indol-5-yl)-3-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazole (antibiotic 75b) was efficacious in a mouse model of MRSA infection, exhibiting a long half-life, a high volume of distribution, and low clearance. This antibiotic is bactericidal and is orally bioavailable in mice. This class of antibiotics holds great promise in recourse against infections by MRSA.

Discovery of a new class of non-β-lactam inhibitors of penicillin-binding proteins with gram-positive antibacterial activity

Infections caused by hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) are a serious global public-health concern, as MRSA has become broadly resistant to many classes of antibiotics. We disclose herein the discovery of a new class of non-β-lactam antibiotics, the oxadiazoles, which inhibit penicillin-binding protein 2a (PBP2a) of MRSA. The oxadiazoles show bactericidal activity against vancomycin-and linezolid-resistant MRSA and other Gram-positive bacterial strains, in vivo efficacy in a mouse model of infection, and have 100% oral bioavailability.

Selective one-pot access to symmetrical or unsymmetrical diaryl ethers by copper-catalyzed double arylation of a simple oxygen source

Great CO-mbination: A novel method is reported for the controlled one-pot synthesis of various symmetrical or unsymmetrical diaryl ethers by double arylation of a simple inorganic oxygen source (see scheme). This versatile and highly selective process is based on the use of a cheap and low toxicity copper catalytic system.

ANTIBACTERIAL COMPOUNDS AND METHODS OF USING SAME

Embodiments of the present invention provide novel antibacterials that target penicillin-binding proteins or other important cellular targets. Methods for inhibiting growth (reproduction, etc.) of bacteria using compounds described herein are also provided. Various embodiments exhibit activity against gram positive bacteria, such as certain strains of Entercoccus and Staphylococcus aureus.

ANTIBACTERIAL COMPOUNDS AND METHODS OF USING SAME

Embodiments of the present invention provide novel antibactehals that target penicillin-binding proteins or other important cellular targets. Methods for inhibiting growth (reproduction, etc.) of bacteria using compounds described herein are also provided. Various embodiments exhibit activity against gram positive bacteria, such as certain strains of Entercoccus and Staphylococcus aureus.

Diaryl ether synthesis in supercritical carbon dioxide in batch and continuous flow modes

A high yielding, batch mode synthesis of diaryl ethers and sulfides by an SNAr fluoride-mediated process in scCO2 has been developed; the use of a polymer-supported imidazolium fluoride reagent in batch mode led to the development of

Synthesis of diaryl ethers, diaryl sulfides, heteroaryl ethers and heteroaryl sulfides under microwave dielectric heating

This paper describes the synthesis of diaryl ethers and sulfides by utilizing microwave heating methodology. The methodology is shown to be rapid and efficient for the coupling of phenols or thiophenol with electron-deficient aryl halides through a SNAr reaction. The scope of the protocol can be expanded to six-membered heterocycles bearing a hydroxyl group as well as to the reaction of 2-pyrimidinethiol with mildly activated aryl halides, providing heteroaryl ethers and sulfides, respectively. The advantages of the present method include the wide substrate scope, the obviation of metal catalysts, ease of product isolation, and high purity of products. Georg Thieme Verlag Stuttgart.