Facile synthesis of 4‐alkoxycarbonylisoquinoline‐1,3‐diones and 5‐alkoxycarbonyl‐2‐benzazepine‐1,3‐diones <i>via</i> a mild alkaline cyclization

Billamboz, Muriel; Bailly, Fabrice; Cotelle, Philippe

doi:10.1002/jhet.52

Cited by 7 publications

(6 citation statements)

References 14 publications

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“…N -Benzyloxyamide intermediates II were obtained by two pathways. The first one was based upon a formerly reported route for the preparation of 4-alkoxycarbonylisoquinoline-1,3-diones and was used only for the synthesis of 4 (Scheme ). 4-Hydroxyhomophthalic acid 1 , obtained in three steps from homophthalic acid, was successively esterified and etherified to give intermediate 2 .…”

Section: Chemistrymentioning

confidence: 99%

Investigation of a Novel Series of 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as Human Immunodeficiency Virus Type 1 Integrase Inhibitors

et al. 2014

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We report herein further insight into the biological activities displayed by a series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs). Substitution of the N-hydroxyimide two-metal binding pharmacophore at position 4 by carboxamido side chains was previously shown by us to be fruitful for this scaffold, since strong human immunodeficiency virus type 1 integrase (HIV-1 IN) inhibitors in the low nanomolar range associated with low micromolar anti-HIV activities were obtained. We investigated the influence of substitution at position 7 on biological activity. Introduction of electron-withdrawing functional groups such as the nitro moiety at position 7 led to a noticeable improvement of antiviral activity, down to low nanomolar anti-HIV potencies, with advantageous therapeutic indexes going close to those of the clinically used raltegravir and retained potencies against a panel of IN mutants.

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Section: Chemistrymentioning

confidence: 99%

Investigation of a Novel Series of 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as Human Immunodeficiency Virus Type 1 Integrase Inhibitors

et al. 2014

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“…The synthetic pathway was based upon a formerly reported route for the synthesis of 4-alkoxycarbonylisoquinoline-1,3diones. 15 Acid precursor 1 was obtained in two steps from commercial homophthalic acid. After coupling of O-benzylhydroxylamine, ammonia, or N-methylamine, the corresponding amides 2−4 were quantitatively cyclized in mild alkaline conditions into ester precursors 5−7 (Scheme 1).…”

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confidence: 99%

“…The synthetic pathway was based upon a formerly reported route for the synthesis of 4-alkoxycarbonylisoquinoline-1,3-diones . Acid precursor 1 was obtained in two steps from commercial homophthalic acid.…”

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confidence: 99%

4-Substituted 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as a Novel Class of HIV-1 Integrase Inhibitors

Billamboz

Suchaud

Bailly

et al. 2013

ACS Med. Chem. Lett.

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A series of 2-hydroxy-1,3-dioxoisoquinoline-4-carboxamides featuring an N-hydroxyimide chelating functionality was evaluated for their inhibitory properties against human immunodeficiency virus type 1 integrase (HIV-1 IN). Several derivatives displayed low nanomolar IC 50 values comparable to that of the clinically used raltegravir. A marked effect of one compound on both primary IN-catalyzed reactions, strand transfer (ST), and 3′ processing (3′-P), emphasizes a novel IN inhibition mechanism establishing it as a potential new generation IN inhibitor. Substitution of the 2-hydroxyisoquinoline-1,3-dione scaffold at position 4 by carboxamido chains was beneficial for antiviral activity since reproducible low micromolar anti-HIV activities were obtained for the first time within this scaffold.

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“…A mixture of dimethyl homophthalate (33 mmol, 7.0 g) prepared as described previously 17 and NBS (57 mmol, 10.2 g) in anhydrous CH 2 Cl 2 (170 mL) was stirred under reflux by irradiating with an UV-light lamp. After 18 h, the solution was filtered off and the filtrate was sequentially washed with aq 10% NaHCO 3 (50 mL), aq 10% NaHSO 3 (50 mL), and brine (50 mL).…”

Section: Dimethyl α-Bromohomophthalate (1)mentioning

confidence: 99%

From Liquid to Solid-State Fluorescence: Tricyclic Lactones Based on 4-Hydroxy-1,3-thiazoles

et al. 2013

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This work describes the synthesis of a series of tricyclic lactones based on 4-hydroxy-1,3-thiazoles prepared by the classic Hantzsch synthesis. The tricyclic lactones are more rigid than the parent 4-hydroxythiazoles and are featured not only by fluorescence in solution, but also in the solid state. An extension of the chromophoric system was successfully realized by integration of the benzothiazole substructure, thus resulting in bathochromic shifts of absorption and also fluorescence. The new synthesized lactones additionally show interesting properties in solution, whereby the initial blue fluorescence changes dramatically with a variation of the pH value.Key words: heterocycles, chromophores, fused-ring systems, thiazole, fluorescence 4-Hydroxy-1,3-thiazoles and their derivatives have been intensively studied in the last few years, because they represent a new class of functional fluorophores. 1,2In addition, they form the substructure of several natural products and were chosen by nature as part of the chemical compound responsible for the dual luminescence of the firefly (lampyridae). 3The remarkable spectroscopic properties of this heterocycle as fluorophore and chromophore, and its easy feasibility of functionalization enable the development of a variety of novel applications. They have been used as novel ligands for metal complexes, emitting polymers, dyes, and sensors. [4][5][6][7][8] Furthermore, it is known that the extension of the π-system attached to the thiazole ring by substitution with aromatic heterocycles allows the modification of its photophysical properties. 3,7Consequently, we were interested in the synthesis of a new class of thiazole-based derivatives containing a ringfused π-system. The reaction of dimethyl α-bromohomophthalate with various thioamides should be suitable in order to obtain annulated thiazoles by intramolecular esterification. In contrast to most of the fluorescent dyes described in literature, 9 these novel thiazole derivatives are highly fluorescent in solution as well as in the solid state. Solid-state fluorescence attracts a lot of attention because of its applicability as an emitter material in organic electroluminescence devices (OLEDs), solid-state dye lasers and sensor materials, and the potential use in the construction of optoelectronic devices. 9,10 It is well known that the photophysical properties of these compounds depend strongly on the nature of their conjugated π-system, their geometry in the solid state, and their packing in the crystal. 10c,dThe tricyclic lactones based on 4-hydroxy-1,3-thiazoles were synthesized according to the classic Hantzsch synthesis 3 in moderate up to good yields (79%). As depicted in Scheme 1, different thioamides 2 react with dimethyl α-bromohomophthalate (1) in DMF in the presence of triethylamine at 120°C to furnish the tricyclic lactones 4. In order to get more information about the influence of an extended π-system, the benzo[d]thiazole-2-carbothioamides 3 were used to obtain the lactones 5. The new tricycli...

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Facile synthesis of 4‐alkoxycarbonylisoquinoline‐1,3‐diones and 5‐alkoxycarbonyl‐2‐benzazepine‐1,3‐diones via a mild alkaline cyclization

Cited by 7 publications

References 14 publications

Investigation of a Novel Series of 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as Human Immunodeficiency Virus Type 1 Integrase Inhibitors

Investigation of a Novel Series of 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as Human Immunodeficiency Virus Type 1 Integrase Inhibitors

4-Substituted 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as a Novel Class of HIV-1 Integrase Inhibitors

From Liquid to Solid-State Fluorescence: Tricyclic Lactones Based on 4-Hydroxy-1,3-thiazoles

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