AN IMPROVED METHOD FOR THE SYNTHESIS OF 3-AMINO-1<i>H</i>-QUINOLIN-2-ONE

Juarez‐Gordiano, Cecilia; Hernández‐Campos, Alicia; Castillo, Rafael

doi:10.1081/scc-120012984

Cited by 6 publications

(2 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because 5-oxazolone is susceptible to nucleophilic attack, we recovered the o -amino group after the 5-oxazolone was converted to 5-imidazolone. In this retro-synthesis, o - 2a was been obtained by Gucky via step 1 .…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Photophysical Properties, and Application of o- and p-Amino Green Fluorescence Protein Synthetic Chromophores

Chen

Sung

2012

J. Org. Chem.

View full text Add to dashboard Cite

The o- and p-amino green-fluorescence-protein synthetic chromophores (GFPSCs) were synthesized from the corresponding o- and p-nitro protecting group. Among the four protecting groups of the o-amino group, the o-nitro protecting group is the only choice to synthesize the o-amino GFPSCs. The first singlet excited states of o- and p-amino GFPSCs carry significant charge-transfer character through the mechanism of photoinduced charge transfer (PCT). The o-amino GFPSCs can serve as wavelength-ratiometric fluorescence sensors that selectively recognize Cr(3+) in aqueous medium through a PCT mechanism.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis, Photophysical Properties, and Application of o- and p-Amino Green Fluorescence Protein Synthetic Chromophores

Chen

Sung

2012

J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…Using an uncharacterized substrate (3-aminoquinoline), we demonstrate the utility of ecoAO to generate milligram quantities of AO metabolite from frozen cell paste reconstituted in buffer that can be used as starting material for the synthesis of more complex molecules. The biotranformation of 3-aminoquinoline, post-ecoAO 2-oxo-3-aminoquinoline analogue synthesis (Scheme ), and ecoAO metabolism of the 3-aminoquinoline analogues, illustrate two important points: (1) these metabolites could not be synthesized by the same method as was used for zoniporide (see Scheme ), although a 4-step synthesis has been reported and (2) even relatively sterically hindered compounds readily undergo oxidation adjacent to the nitrogen. From a broader perspective, the ecoAO system could also be employed in other settings where selective oxidation of azaheterocycles is desired in a synthesis.…”

Section: Discussionmentioning

confidence: 99%

ecoAO: A Simple System for the Study of Human Aldehyde Oxidases Role in Drug Metabolism

et al. 2017

View full text Add to dashboard Cite

Although aldehyde oxidase (AO) is an important hepatic drug-metabolizing enzyme, it remains understudied and is consequently often overlooked in preclinical studies, an oversight that has resulted in the failure of multiple clinical trials. AO’s preclusion to investigation stems from the following: (1) difficulties synthesizing metabolic standards due to the chemospecificity and regiospecificity of the enzyme and (2) significant inherent variability across existing in vitro systems including liver cytosol, S9 fractions, and primary hepatocytes, which lack specificity and generate discordant expression and activity profiles. Here, we describe a practical bacterial biotransformation system, ecoAO, addressing both issues simultaneously. ecoAO is a cell paste of MoCo-producing Escherichia coli strain TP1017 expressing human AO. It exhibits specific activity toward known substrates, zoniporide, 4-trans-(N,N-dimethylamino)cinnamaldehyde, O6-benzylguanine, and zaleplon; it also has utility as a biocatalyst, yielding milligram quantities of synthetically challenging metabolite standards such as 2-oxo-zoniporide. Moreover, ecoAO enables routine determination of kcat and V/K, which are essential parameters for accurate in vivo clearance predictions. Furthermore, ecoAO has potential as a preclinical in vitro screening tool for AO activity, as demonstrated by its metabolism of 3-aminoquinoline, a previously uncharacterized substrate. ecoAO promises to provide easy access to metabolites with the potential to improve pharmacokinetic clearance predictions and guide drug development.

show abstract