Gyula Horvath

New Non Competitive AMPA Antagonists

New halogen atom substituted 2,3-benzodiazepine derivatives condensed with an azole ring on the seven membered part of the ring system of type 3 and 4 as well as 5 and 6 were synthesized. It was found that chloro-, dichloro- and bromo-substitutions in the benzene ring and additionally imidazole ring condensation on the diazepine ring can successfully substitute the methylenedioxy group in the well known molecules GYKI 52466 (1) and GYKI 53773 (2) and the 3-acetyl-4-methyl structural feature in 2, respectively, preserving the highly active AMPA antagonist characteristic of the original molecules. From the most active compounds (3b,i) 3b (GYKI 47261) was chosen for detailed investigations. 3b revealed an excellent, broad spectrum anticonvulsant activity against seizures evoked by electroshock and different chemoconvulsive agents indicating a possible antiepileptic efficacy. 3b was found to be highly active in a transient model of focal ischemia predictive of a therapeutic value in human stroke. 3b also reversed the dopamine depleting effect of MPTP and antagonized the oxotremorine induced tremor in mice indicating a potential antiparkinson activity.

Synthesis of some diazino-fused tricyclic systems via Suzuki cross-coupling and regioselective nitrene insertion reactions

Suzuki coupling of 5-chloro-2-methyl-6-phenylpyridazin-3(2H)-one, 6-chloro-1,3-dimethyluracil and 2-chloropyrazine with protected aminoaryl boronic acids resulted in the corresponding pivaloylaminophenyl diazines which were transformed to diazino-fused indole and cinnoline derivatives. Suzuki coupling of 5-amino-6-chloro-1,3-dimethyluracil with 2-formylphenyl boronic acid afforded a novel pyrimidoisoquinoline ring system in a one-pot reaction.

Studies on calix(aza)crowns, II. Synthesis of novel proximal doubly bridged calix[4]arenes by intramolecular ring closure of syn 1,3-and 1,2-ω-chloroalkylamides☆

Inherently chiral calix[4]arenes (9,10) with carboxamide bridges spanning the proximal positions on the lower rim and 18 achiral counterparts have been synthesized by double intramolecular cyclization of 7b,8b 1,3-and 17 1,2-bis-chloroalkylamides. The conformational analysis of the 1.3- and 1,2-disubstituted calixarene intermediates 5–8 and 15–17 proved an equilibrium of two distorted cone conformations. The success of ring closure was strictly dependent on the chain length of the open chain precursors.

Synthesis and Structure Elucidation of Chromogenic Calix[4]arene Indophenols Capped by Carboxamide Bridges

Calix[4]arenes capped by di- and triamide bridges on the lower rim were used to synthesize 2,3,4,5 chromogenic molecules supplied with indophenol indicator unit(s). The endo/exo quinoid tautomerism of the chromophore and the mechanism of the coloration process were studied by NMR spectroscopy.

STRUCTURE OF A FURTHER TRITERPENE SAPONIN FROM ARENARIA FILICAULIS BOISS.

A novel triterpenoid saponin, Snatzkein E, was isolated from Arenaria filicaulis Boiss. It possesses a new aglycone and a glucose moiety carrying a sulfate group at C‐2′. Its structure and conformational behaviour were investigated by one‐ and two‐dimensional 1H and 13C NMR spectroscopy.

Studies on Calix(aza)crqwns, III. Synthesis of 1,3-Alternate Calix[4]arenes Capped by Diamide Bridges

Abstract The akylation of calix[4]arenes 1 capped by diamide bridges gave fully substituted compounds 5 and 6 of 1,3-alternate conformation. Diesters 6 were cyclized with diamines to afford doubly capped derivatives 7.

Reaction of aminothiazole-oximetosylates with thiols

The reaction of ethyl 2-(2-acetyl- or 2-formyl-amidothiazol-4-yl)-2-tosyloxyiminoacetate with thiols in the presence of triethylamine gave the corresponding sulfenylimines. When acetone was used as solvent the reaction led to 2,2-dimethyl-4-(2-acetyl- or 2-formyl-amido-thiazol-4-yl)-5-oxo-2,5-dihydro-1,3-oxazole. In 2-butanone or cyclohexanone similar oxazolinone derivatives were obtained. The structure of the products was elucidated by ir, 1H-and 13C-nmr spectroscopy, and a reaction mechanism is suggested for their formation.

Structure Determination of Zinc Complexes of Iminodiacetamide Ionophores in Solution and in the Solid State

It is shown by extensive NMRinvestigation that hexa-coordinatedZn2+-complexes containing two tridentateiminodiacetamide ligands adopt a solutionconformation with two different kinds ofZn–O bonds possessing a center ofinversion. In contrast, the complexmolecules are chiral in the solid state asdetermined by CP-MAS 13C NMR spectroscopy.