Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Inhibition of myeloperoxidase: evaluation of 2H-indazoles and 1H-indazolones.

ABSTRACT: Myeloperoxidase (MPO) produces hypohalous acids as a key component of the innate immune response; however, release of these acids extracellularly results in inflammatory cell and tissue damage. The two-step, one-pot Davis-Beirut reaction was used to synthesize a library of 2H-indazoles and 1H-indazolones as putative inhibitors of MPO. A structure-activity relationship study was undertaken wherein compounds were evaluated utilizing taurine-chloramine and MPO-mediated H2O2 consumption assays. Docking studies as well as toxicophore and Lipinski analyses were performed. Fourteen compounds were found to be potent inhibitors with IC50 values <1?M, suggesting these compounds could be considered as potential modulators of pro-oxidative tissue injury pertubated by the inflammatory MPO/H2O2/HOCl/HOBr system.

SUBMITTER: Roth A

PROVIDER: S-EPMC4254468 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Inhibition of myeloperoxidase: evaluation of 2H-indazoles and 1H-indazolones.

Roth Aaron A Ott Sean S Farber Kelli M KM Palazzo Teresa A TA Conrad Wayne E WE Haddadin Makhluf J MJ Tantillo Dean J DJ Cross Carroll E CE Eiserich Jason P JP Kurth Mark J MJ

Bioorganic & medicinal chemistry 20141002 22

Myeloperoxidase (MPO) produces hypohalous acids as a key component of the innate immune response; however, release of these acids extracellularly results in inflammatory cell and tissue damage. The two-step, one-pot Davis-Beirut reaction was used to synthesize a library of 2H-indazoles and 1H-indazolones as putative inhibitors of MPO. A structure-activity relationship study was undertaken wherein compounds were evaluated utilizing taurine-chloramine and MPO-mediated H2O2 consumption assays. Dock ...[more]

PMID: 25438766

Similar Datasets

Synthesis of 2-Alkenyl-2H-indazoles from 2-(2-Carbonylmethyl)-2H-indazoles.

Project description:A procedure has been developed for synthesis of 2-alkenyl-2H-indazoles starting from 2-(2-carbonylmethyl)-2H-indazoles, which are prepared by gallium/aluminium- and aluminium-mediated, direct, regioselective alkylation of indazoles with ?-bromocarbonyl compounds. The structure of 3-(2H-indazol-2-yl)-2H-chromen-2-one was proven by X-ray crystallography. The styrene- and coumarin-2H-indazoles produced by using the new method were found to have interesting fluorescence properties.

| S-EPMC6273450 | biostudies-literature

Osmium(IV) complexes with 1H- and 2H-indazoles: tautomer identity versus spectroscopic properties and antiproliferative activity.

Project description:A one-pot synthesis of osmium(IV) complexes with two different tautomers of indazole, 1H-indazole and 2H-indazole, namely (H(2)ind)[Os(IV)Cl(5)(2H-ind)] (1) and (H(2)ind)[Os(IV)Cl(5)(1H-ind)] (2) is reported. Both compounds have been comprehensively characterized by NMR spectroscopy, ESI (electrospray ionization) mass spectrometry, electronic absorption spectroscopy, IR spectroscopy, cyclic voltammetry and tested for antiproliferative activity in vitro in three human cancer cell lines, CH1 (ovarian carcinoma), A549 (non-small cell lung cancer) and SW480 (colon carcinoma), as well as in vivo in a Hep3B SCID mouse xeno-transplantation model. 2H-Indazole tautomer stabilization in 1 has been confirmed by X-ray diffraction.

| S-EPMC3400055 | biostudies-literature

The Davis-Beirut reaction: N1,N2-disubstituted-1H-indazolones via 1,6-electrophilic addition to 3-alkoxy-2H-indazoles.

Project description:A variety of electrophiles (anhydrides, acid chlorides, carbonochloridates, sulfonyl chlorides, and alkyl bromides) react with 3-methoxy-2H-indazole (1a), benzoxazin[3,2-b]indazole (1d), and oxazolino[3,2-b]indazole (1e)?-?substrates available by the Davis-Beirut reaction?-?to yield a diverse set of N(1),N(2)-disubstituted-1H-indazolones. With certain electrophiles, an AERORC (Addition of the Electrophile, Ring Opening, and Ring Closure) process on indazole 1d results in indazoloindazolone formation. An intriguing aspect of these N(1),N(2)-disubstituted-1H-indazolones is that they are poised for diversification through, for example, azide-alkyne cycloaddition chemistry reported here.

| S-EPMC3112251 | biostudies-literature

Syntheses of 1-Aryl-5-nitro-1H-indazoles and a General One-Pot Route to 1-Aryl-1H-indazoles.

Project description:An efficient route to substituted 1-aryl-1H-indazoles has been developed and optimized. The method involved the preparation of arylhydrazones from acetophenone or benzaldehyde substituted by fluorine at C2 and nitro at C5, followed by deprotonation and nucleophilic aromatic substitution (SNAr) ring closure in 45-90%. Modification of this procedure to a one-pot domino process was successful in the acetophenone series (73-96%), while the benzaldehyde series (63-73%) required a step-wise addition of reagents. A general one-pot protocol for 1-aryl-1H-indazole formation without the limiting substitution patterns required for the SNAr cyclization has also been achieved in 62-78% yields. A selection of 1-aryl-1H-indazoles was prepared in high yield by a procedure that requires only a single laboratory operation.

| S-EPMC6017161 | biostudies-literature

Davis-Beirut reaction: route to thiazolo-, thiazino-, and thiazepino-2H-indazoles.

Project description:Methods for the construction of thiazolo-, thiazino-, and thiazepino-2H-indazoles from o-nitrobenzaldehydes or o-nitrobenzyl bromides and S-trityl-protected 1°-aminothioalkanes are reported. The process consists of formation of the requisite N-(2-nitrobenzyl)(tritylthio)alkylamine, subsequent deprotection of the trityl moiety with TFA, and immediate treatment with aq. KOH in methanol under Davis-Beirut reaction conditions to deliver the target thiazolo-, thiazino-, or thiazepino-2H-indazole in good overall yield. Subsequent S-oxidation gives the corresponding sulfone.

| S-EPMC4120971 | biostudies-literature

One-pot synthesis of novel 2,3-dihydro-1H-indazoles.

Project description:A copper(I)-mediated one-pot synthesis of 2,3-dihydro-1H-indazole heterocycles has been developed. This synthetic route provides the desired indazoles in moderate to good yields (55%-72%) which are substantially better than those achievable with an alternative two-step reaction sequence. The reaction is tolerant of functionality on the aromatic ring.

| S-EPMC6264256 | biostudies-literature

A one-pot-three-step route to triazolotriazepinoindazolones from oxazolino-2H-indazoles.

Project description:A one-pot-three-step method has been developed for the conversion of oxazolino-2H-indazoles into triazolotriazepinoindazolones with three points of diversity. Step one of this process involves a propargyl bromide-initiated ring opening of the oxazolino-2H-indazole (available by the Davis-Beirut reaction) to give an N(1)-(propargyl)-N(2)-(2-bromoethyl)-disubstituted indazolone, which then undergoes -CH(2)Br ? -CH(2)N(3) displacement (step two) followed by an uncatalyzed intramolecular azide-alkyne 1,3-dipolar cycloaddition (step three) to form the target heterocycle. Employing 7-bromooxazolino-2H-indazole allows for further diversification through, for example, palladium-catalyzed coupling chemistry, as reported here.

| S-EPMC3427757 | biostudies-literature

Synthesis of 2H-indazoles by the [3 + 2] cycloaddition of arynes and sydnones.

Project description:A rapid and efficient synthesis of 2H-indazoles has been developed, which involves the [3 + 2] dipolar cycloaddition of arynes and sydnones. The process proceeds under mild reaction conditions in good to excellent yields.

| S-EPMC2871071 | biostudies-literature

Synthesis of 2H-indazoles by the [3 + 2] dipolar cycloaddition of sydnones with arynes.

Project description:A rapid and efficient synthesis of 2H-indazoles has been developed using a [3 + 2] dipolar cycloaddition of sydnones and arynes. A series of 2H-indazoles have been prepared in good to excellent yields using this protocol, and subsequent Pd-catalyzed coupling reactions can be applied to the halogenated products to generate a structurally diverse library of indazoles.

| S-EPMC3209955 | biostudies-literature

Davis-Beirut Reaction: A Photochemical Bronsted Acid Catalyzed Route to N-Aryl 2H-Indazoles.

Project description:The Davis-Beirut reaction provides access to 2H-indazoles from aromatic nitro compounds. However, N-aryl targets have been traditionally challenging to access due to competitive alternate reaction pathways. Previously, the key nitroso imine intermediate was generated under alkaline conditions, but as reported here, the photochemistry of o-nitrobenzyl alcohols empowered Brønsted acid catalyzed conditions for accessing N-aryl targets. Anilines and alkyl amines give different outcomes under optimized conditions; the proposed mechanism was studied using quantum chemical calculations.

| S-EPMC6698363 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data