181765-85-5Relevant academic research and scientific papers
A photoredox-neutral Smiles rearrangement of 2-aryloxybenzoic acids
Gonzalez-Gomez, Jose C.,Ramirez, Nieves P.,Lana-Villarreal, Teresa,Bonete, Pedro
supporting information, p. 9680 - 9684 (2017/11/30)
We report on the use of visible light photoredox catalysis for the radical Smiles rearrangement of 2-aryloxybenzoic acids to obtain aryl salicylates. The method is free of noble metals and operationally simple and the reaction can be run under mild batch or flow conditions. Being a redox neutral process, no stoichiometric oxidants or reductants are needed.
Synthesis and antimicrobial evaluation of amixicile-based inhibitors of the pyruvate-ferredoxin oxidoreductases of anaerobic bacteria and Epsilonproteobacte
Kennedy, Andrew J.,Bruce, Alexandra M.,Gineste, Catherine,Ballard, T. Eric,Olekhnovich, Igor N.,Macdonald, Timothy L.,Hoffman, Paul S.
supporting information, p. 3980 - 3987 (2016/07/11)
Amixicile is a promising derivative of nitazoxanide (an antiparasitic therapeutic) developed to treat systemic infections caused by anaerobic bacteria, anaerobic parasites, and members of the Epsilonproteobacteria (Campylobacter and Helicobacter). Amixicile selectively inhibits pyruvate-ferredoxin oxidoreductase (PFOR) and related enzymes by inhibiting the function of the vitamin B1 cofactor (thiamine pyrophosphate) by a novel mechanism. Here, we interrogate the amixicile scaffold, guided by docking simulations, direct PFOR inhibition assays, and MIC tests against Clostridium difficile, Campylobacter jejuni, and Helicobacter pylori. Docking simulations revealed that the nitro group present in nitazoxanide interacts with the protonated N4′-aminopyrimidine of thiamine pyrophosphate (TPP). The ortho-propylamine on the benzene ring formed an electrostatic interaction with an aspartic acid moiety (B456) of PFOR that correlated with improved PFOR-inhibitory activity and potency by MIC tests. Aryl substitution with electron-withdrawing groups and substitutions of the propylamine with other alkyl amines or nitrogen-containing heterocycles both improved PFOR inhibition and, in many cases, biological activity against C. difficile. Docking simulation results correlate well with mechanistic enzymology and nuclear magnetic resonance (NMR) studies that show members of this class of antimicrobials to be specific inhibitors of vitamin B1 function by proton abstraction, which is both novel and likely to limit mutation-based drug resistance.
COMPOUNDS AND METHODS FOR TREATING HIV INFECTIONS
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Paragraph 0451, (2015/04/21)
The present invention is directed to novel nanomolar and picomolar inhibitors of HIV reverse transcriptase, pharmaceutical compositions therefrom and methods for inhibiting reverse transcriptase and treating HIV infections, especially included drug resistant strains of HIV-1 and HIV-2 and/or secondary disease states and/or conditions which occur as a consequence of HIV infection.
Picomolar inhibitors of HIV-1 reverse transcriptase: Design and crystallography of naphthyl phenyl ethers
Lee, Won-Gil,Frey, Kathleen M.,Gallardo-Macias, Ricardo,Spasov, Krasimir A.,Bollini, Mariela,Anderson, Karen S.,Jorgensen, William L.
supporting information, p. 1259 - 1262 (2015/04/27)
Catechol diethers that incorporate a 6-cyano-1-naphthyl substituent have been explored as non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). Promising compounds are reported that show midpicomolar activity against the wild-type virus and sub-20 nM activity against viral variants bearing Tyr181Cys and Lys103Asn mutations in HIV-RT. An X-ray crystal structure at 2.49 ? resolution is also reported for the key compound 6e with HIV-RT.
BENZODIAZEPINONES AS FAK INHIBITORS FOR TREATMENT OF CANCER
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Page/Page column 64-65, (2012/04/23)
Disclosed are compounds which inhibit the activity of focal adhesion kinase, compositions containing the compounds, and methods of treating diseases during which focal adhesion kinase is expressed.
COMPOUNDS, COMPOSITIONS, AND METHODS
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Page 67-68, (2008/06/13)
Compounds useful for treating cellular proliferative diseases and disorders by modulating the activity of KSP are disclosed.
