Synthesis of 6-Ethyl-1,2,9-trioxopyrrolo[3,2-f ]quinoline-8-carboxylic Acid

Abstract

Interaction of 6-amino-1-ethyl-4-oxoquinoline-3-carboxylic ester (7) with chloral hydrate and hydroxylamine hydrochloride gave the corresponding isonitroso-acetamido derivative 8 which, upon treatment with concentrated sulfuric acid, was converted regioselectively into 1,2,9-trioxopyrrolo[3,2-f ]quinoline-8-carboxylic acid (3). This novel tricyclic system was isolated in good yield as a stable hydrate 3H. Structural assignments of the new compounds are based on microanalytical and spectral (MS and NMR) data.

Synthesis and Biological Evaluation of New Pyridone-Annelated Isoindigos as Anti-Proliferative Agents

“…The key intermediate in this synthesis is 6-ethyl-1,2,9-trioxopyrrolo[3,2- f ]quinoline-8-carboxylic acid (1 ), the preparation of which has been recently reported [17]. The targeted isoindigos 3a – f were synthesized by acid-catalyzed crossed aldol–condensation reaction between 6-ethyl-1,2,9-trioxopyrrolo[3,2- f ]quinoline-8-carboxylic acid ( 1 ) [17] and the appropriate oxindoles 2a – f under reflux (Scheme 1). The new compounds 3a – f were characterized by elemental analyses, MS and NMR spectral data.…”

“…The title compound has been prepared in two-steps starting with ethyl 6-amino-1-ethyl-4-oxo-1,4-dihydroquinoline-3-carboxylate according to the method described by Sandmeyer [33,34], and following the published procedure [17].…”

“…Accordingly, and in line with developing new isoindigos, we thought it was worthwhile to prepare some pyridone-annelated isoindigos to evaluate their antitumor activities. Herein, we report on the synthesis of new pyridone-annelated isoindigo derivatives, namely the 6-ethyl-2,9-dioxo-1-(2'-oxoindolin-3'-ylidene)-2,3,6,9-tetrahydro-1 H -pyrrolo[3,2- f ]quinoline-8-carboxylic acids 3a – f using the acid-catalyzed reactions of 6-ethyl-1,2,9-trioxopyrrolo[3,2- f ]quinoline-8-carboxylic acid ( 1 ) [17] with oxindoles 2a – f (Scheme 1), and the evaluation of their antiproliferative activities against the human chronic myelogenous leukemia K562 and other hematological and solid tumor cell lines. We show that two of our synthesized compounds having a chlorine and bromine substitution at the 5'-position of the benzo-ring E, effectively inhibit proliferation of K562 cells in a dose- and time-dependent fashion with IC 50 values ranging from 4 to 19 µM, depending on the exposure time to the compound.…”

N-Adamantyl-1-alkyl-4-oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as Fluorescent Probes to Detect Microglia Activation through the Imaging of Cannabinoid Receptor Subtype 2 (CB2R)

“…The synthesis of key intermediates ( 23a – 28a, 29b – e ) leading to fluorescent final compounds ( 30a – 33a, 34b – e ; 35a – 46a ) is reported in Scheme . The key intermediates 4-oxo-1,4-dihydroquinolines ( 2a – e ) were obtained as previously reported. − Afterward, they were alkylated with the proper alkyl-dibromides under microwave irradiation affording the N -bromoalkyl-4-oxo-dihydroquinolone derivatives ( 3a – 6a ; 7b – e ). The reaction of these N -alkyl-bromides with NaN 3 provided the corresponding azidohexyl derivatives ( 8a – 11a ; 12b – e ) whose ester function was hydrolyzed under basic conditions to the corresponding carboxylic acids ( 13a – 16a ; 17b – e ).…”

“…1 H NMR (300 MHz, CDCl 3 ) δ: 1. 31 Ethyl 6-(2,5-Dimethyl-1H-pyrrol-1-yl)-4-oxo-1-pentyl-1,4-dihydroquinoline-3-carboxylate (50). Compound 49 (0.5 g, 1.6 mmol), 1-bromopentane (0.6 mL, 4.63 mmol), and K 2 CO 3 (0.64 g, 4.63 mmol) were weighted altogether in a 10−20 mL microwave vial and CH 3 CN (10 mL) was added.…”