1-Substituted 4-[Chloropyrazolyl][1,2,4]triazolo[4,3-a]quinoxalines: Synthesis and Structure-Activity Relationships of a New Class of Benzodiazepine and Adenosine Receptor Ligands

Matuszczak, Barbara; Pekala, E.; Müller, Christa E.

doi:10.1002/(sici)1521-4184(199805)331:5<163::aid-ardp163>3.0.co;2-3

Cited by 15 publications

(11 citation statements)

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“…amounts of Br 2 /AcOH or ICl/AcOH afforded [4-bromo-3-(3-chloroquioxalin-2-yl)-1-phenyl-1H-pyrazol-5-yl]methyl acetate (9a) and [3-(3-chloroquioxalin-2-yl)-4-iodo-1-phenyl-1H-pyrazol-5-yl]methyl acetate (9b), respectively, via the electrophilic attack of the active 4-position of the pyrazole ring. The reaction of 9a and 9b with benzoylhydrazine gave {3- [3-(2-benzoylhydrazinyl)quinoxalin-2-yl]-4-halo-1phenyl-1H-pyrazol-5-yl}methyl acetate 10a and 10b, which underwent dehydrative cyclization on boiling with acetic anhydride to yield [4-halo-1-phenyl-3-(1-phenyl-[1,2,4]triazolo [4,3-a]quioxalin-4-yl)-1H-pyrazol-5-yl]methyl acetate (11). The structures of 10 and 11 were confirmed from their spectral analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Yield (80%); m.p. 285-286 C; IR: 1741 (COO), 1660 (CON), and 1587 cm À1 (C¼ ¼C); 1 H-NMR (CDCl 3 ): d ¼ 2.00 (s, 3H, OAc), 5.25 (s, 2H, CH 2 ), 7.43-7.88 (m, 14H, Ar-H), 11.79 (s, 1H, NH, exchangeable), and 12.17 (s,1H,NH,exchangeable) General procedure for the preparation of [4-halo-1-phenyl-3-(1-phenyl- [1,2,4]-triazolo [4,3-a]quioxalin-4-yl)-1H-pyrazol-5-yl]methyl acetate (11). A solution [3-(3-(2-benzoylhydrazinyl)quinoxalin-2-yl)-4-halo-1-phenyl-1H-pyrazol-5yl]methyl acetate (10, 0.001 mol) in acetic anhydride (3 mL) was heated under reflux for 1 h. The mixture was then cooled and poured onto crushed ice.…”

Section: Methodsmentioning

confidence: 99%

“…A triazoloquinoxalinone moiety has been investigated for an antagonist receptor modeling study [7]. Moreover, derivatives of 1,2,4-triazolo[4,3-a]quinoxalines have been reported as anti-inflammatory drugs, allergy inhibitors [8], fungicides [9], for treating glycogen synthase kinase 3-mediated conditions [10], and submicromolar affinity for the benzodiazepine-binding site of GABAA receptors [11] as well as potential antagonist ligands for imaging the A2A adenosine receptor by position emission tomography [12]. The bis-triazoloquinoxalines showed antifungal activity [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of 4‐(1‐phenyl‐1H‐pyrazol‐3‐yl)‐[1,2,4]triazolo[4,3‐a]quinoxalines and their 4‐halogenopyrazolyl analogs

Atta

Ashry

2011

Journal of Heterocyclic Chem

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in Wiley Online Library (wileyonlinelibrary.com). Synthesis of {3-[1-(ethoxycarbonyl)-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl]-1-phenyl-1H-pyrazol-5-yl}methyl ethyl oxalate (2), ethyl 4-[5-(acetoxymethyl)-1-phenyl-1H-pyrazol-3-yl]-[1,2,4]triazolo[4,3a]quioxaline-1-carboxylate (4), [4-halo-1-phenyl-3-(1-phenyl-[1,2,4]triazolo[4,3-a]quioxalin-4-yl)-1Hpyrazol-5-yl]methyl acetate (11), {4-halo-3-[1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl]-1-phenyl-1H-pyraz-ol-5-yl}methyl acetate (13), and [3-([1,2,4]triazolo-[4,3-a]quinoxalin-4-yl)-4-halo-1-phenyl-1H-pyrazol-5-yl] methyl formate (15) was accomplished. The structural investigation of the new compounds is based on chemical and spectroscopic evidences.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis of 4‐(1‐phenyl‐1H‐pyrazol‐3‐yl)‐[1,2,4]triazolo[4,3‐a]quinoxalines and their 4‐halogenopyrazolyl analogs

Atta

Ashry

2011

Journal of Heterocyclic Chem

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“…The detailed preparation and characterization of the phosphate prodrugs will be described elsewhere. Pharmacologic studies were carried out as described [Müller et al, 1997b;Hauber et al, 1998;Klotz et al, 1998;Matuszczak et al, 1998]…”

Section: Methodsmentioning

confidence: 99%

A2A-selective adenosine receptor antagonists: Development of water-soluble prodrugs and a new tritiated radioligand

Müller¹,

Sauer²,

Maurinsh³

et al. 1998

Drug Dev. Res.

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A2A adenosine receptor (AR) antagonists are promising new drugs for the treatment of Parkinson's disease. Further potential therapeutic indications for A2A AR antagonists include dementias, ischemias, and pain. Potent, selective A2A AR antagonists have been developed, but their generally low water solubility is a major problem for conducting in vivo experiments. We developed a water‐soluble phosphate prodrug (MSX‐3) of a potent, selective A2A AR antagonist (MSX‐2), which is stable in aqueous solution, but rapidly cleaved in vivo by phosphatases to release the active compound MSX‐2. Intracerebral application of MSX‐3 led to a stimulation of motor activity in rats. Catalepsy, induced by pretreatment with either dopamine D1 or D2 antagonist, was potently reversed by intracerebral application of MSX‐3. A new A2A‐selective antagonist radioligand, [3H]MSX‐2, was prepared, which exhibits a KD value of 8 Nm at rat brain striatal membranes. Drug Dev. Res. 45:190–197, 1998. © 1998 Wiley‐Liss, Inc.

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“…It has been reported that l,2,4-triazolo [4,3-a]quinoxaline were found to possess antiallergic (1), antiviral (2,3), anxiolytic (4), inhibition of passive cutaneous anaphylaxis (5) and selective adenosine antagonist (6)(7)(8)(9)(10)(11) activities. Tetrazolo[l,5-a]quinoxalines were also showed fungicidal (12) activities.…”

Section: Introductionmentioning

confidence: 98%

Synthesis and Antimicrobial Activity of Condensed and Uncondensed Quinoxalines

Massry¹

1999

Heterocyclic Communications

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Cyciocondensation of 2-chloro-3-substituted quinoxalines 4 with semicarbazide or phenylacetylhydrazine gave the corresponding l,2,4-triazolo[4,3-a]quinoxalines 5 and 6 . Reaction of 4 with sodium azide afforded tetrazolo[l ,5-a]quinoxalines 7. Heating of 2-hydrazino-3-substituted quinoxalines 9 with diethyl oxalate or acetic anhydride gave the corresponding 3-substituted-l,2,4-triazolo[4,3-a]quinoxalines 12 and 13 respectively. The 2-pyrazolylquinoxaline derivatives 14 were also obtained when 9 was heated with acetylacetone. 3-Benzyl-4-oxo-l 1-substituted-1,2,4-triazino[4,3-a]quinoxalines 16 were obtained upon cyclization of hydrazones 15. with phosphoryl chloride. The prepared compounds were evaluated for antibacterial and antifungal activity.

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1-Substituted 4-[Chloropyrazolyl][1,2,4]triazolo[4,3-a]quinoxalines: Synthesis and Structure-Activity Relationships of a New Class of Benzodiazepine and Adenosine Receptor Ligands

Cited by 15 publications

References 4 publications

Synthesis of 4‐(1‐phenyl‐1H‐pyrazol‐3‐yl)‐[1,2,4]triazolo[4,3‐a]quinoxalines and their 4‐halogenopyrazolyl analogs

Synthesis of 4‐(1‐phenyl‐1H‐pyrazol‐3‐yl)‐[1,2,4]triazolo[4,3‐a]quinoxalines and their 4‐halogenopyrazolyl analogs

A2A-selective adenosine receptor antagonists: Development of water-soluble prodrugs and a new tritiated radioligand

Synthesis and Antimicrobial Activity of Condensed and Uncondensed Quinoxalines

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