József Jeko

New Poly(ADP-ribose) Polymerase-1 Inhibitors with Antioxidant Activity Based on 4-Carboxamidobenzimidazole-2-ylpyrroline and -tetrahydropyridine Nitroxides and Their Precursors

4-Carboxamidobenzimidazoles were previously described as PARP inhibitor compounds. Here we report upon 4-carboxamido-1H-benzimidazoles substituted in the 2-position with nitroxides or their amine or hydroxylamine precursors. Among the new molecules, a highly active PARP inhibitor 4h (IC(50) = 14 nM) was identified with antioxidant/radical scavenger activity. We concluded that in most cases sterically hindered amines are better PARP inhibitors than their oxidized form and structural changes in the 2-substituted 4-carboxamido-1H-benzimidazoles (such as N-substitution or changing the position of the carboxamide group) were detrimental to PARP inhibition activity but not to antioxidant activity. These results indicate the advantages of combining an antioxidant nitroxide or nitroxide precursor with a PARP inhibitor molecule to decrease or eliminate the deleterious processes initiated by reactive oxygen and reactive nitrogen species (ROS and RNS). The radical scavenging capability of 4h was demonstrated by EPR study of urine collected after drug administration.

Synthesis of 4-Aryl-3(5)-(2-hydroxyphenyl)pyrazoles by Reaction of Isoflavones and their 4-Thio Analogues with Hydrazine Derivatives*

4-Aryl-3(5)-2-(hydroxyphenyl)pyrazoles have been prepared by the reaction of isoflavones and their 4-thio analogues with hydrazine hydrate and phenylhydrazine in hot pyridine. The reaction mechanism for the formation of these pyrazoles is discussed. All the new compounds have been fully characterized by NMR spectroscopy. In [D6]DMSO, a 1H NMR study allows observation of the presence of both pyrazole annular tautomers, due to the presence of intramolecular hydrogen bonds in each tautomer (OH···N and NH···O). Theoretical calculations have been carried out on tautomers and conformers of compounds 20 (3(5)-(2-hydroxy-4-methoxyphenyl)-5(3)-methyl-4-phenylpyrazole) and 21 (3(5)-(2-hydroxy-4-methoxyphenyl)-4-(2-methoxyphenyl)-5(3)-methylpyrazole), including the absolute shieldings (GIAO/B3 LYP/6–311++G**) of 21.

DETERMINATION OF THE ABSOLUTE CONFIGURATION OF OPTICALLY ACTIVE 2,2-DIMETHYL-3,4-EPOXYCHROMANS PREPARED BY THE CATALYTIC ENANTIOSELECTIVE EPOXIDATION WITH THE DIMETHYLDIOXIRANE/JACOBSEN MN(III)SALEN SYSTEM

Abstract Enantioselective epoxidation of 2,2-dimethyl-2 H -chromenes 1a-d by using Mn(III)salen complexes (R,R)- 3 and (S,S)- 3 as catalysts and dimethyldioxirane (DMD) as oxygen donor afforded optically active 2,2-dimethyl-3,4-epoxychromans 2a-d in good yields and high enantioselectivities (up to 93% e.e.). The absolute configuration of the (3 S ,4 S )-6,7-bis(tosyloxy)-2,2-dimethyl-3,4-epoxychroman (3S,4S)- 2d has been determined by X-ray diffraction. The absolute configurations of the other nonracemic epoxychromans were assigned by circular dichroism (CD) measurements relative to the (3S,4S)- 2d epoxide as reference compound.

SYNTHESIS OF α-AZIDO-2′-HYDROXYCHALCONES FROM CHALCONE DIBROMIDES WITH AZIDE ION

ABSTRACT The reaction of the 2′-hydroxychalcone dibromides with azide ion was found to afford various products such as α-azido-2′-hydroxychalcones, flavones, aurones, isoxazoles or the parent chalcones depending on the substituent pattern of the substrate. Efficient transformation of α-azido-2′-hydroxychalcones to 3-amino-2-substituted chromones was also demonstrated.

SYNTHESIS AND STUDY OF DOUBLE (EPR ACTIVE AND FLUORESCENT) CHEMOSENSORS IN THE PRESENCE OF Fe3+ ION

The fluorescence properties of 4-aminophthalimide derivatives are influenced by the side-chain attached to the paramagnetic ring or its diamagnetic precursor. PET (photoinduced electron transfer)-induced fluorescence enhancement in the presence of Fe3+ ions was observed only in the case of diamagnetic basic side chain derivatives, since transient metal ions are present in biological systems, only double sensors lacking the above sensitivity are considered as potential reactive oxygen probes.

Synthesis of 2-(2-Thienyl)benzimidazoles by the Reaction of 2-(Mercaptomethyl)benzimidazole With β-Electrophilic Esters

Abstract New 2-(2-di- and tetrahydrothienyl)benzimidazole compounds were prepared by the ring closure reactions of 2-(mercaptomethyl)benzimidazole1,2 (1) and α,β-unsaturated compounds activated with electron-withdrawing groups.

Reductive Formation of 1,5-Benzothiazepines

An unprecedented formation of a new type of 1,5-benzothiazepines with exocyclic double bond at position 4 has been achieved by the reaction of 3-aryl-1-(3-coumarinyl)propen-1-ones with 2-aminothiophenol.

Synthesis and Study of 2-(2-Thienyl)benzazole Type Fluorophores

Abstract Reaction of 2-(mercaptomethyl)benzazoles 2a–c or isothiouronium salt 4 with acetyleneketone 5 or β-halogeno-α,β-unsaturated aldehyde 7 gives highly fluorescent heterocycles 6a–c or 8a–d. The fluorescence properties of these compounds and their aromatised derivatives 9a,b were investigated.

Dimethyldioxirane Oxidation of Exocyclic (E,E)-Cinnamylideneketones

Exocyclic (E,E)-cinnamylideneketones were oxidized by an excess of isolated dimethyldioxirane (DMDO, in acetone solution) at room temperature, providing diastereomeric mixtures of the α,β:γ,δ-diepoxides. In the case of derivatives bearing an ortho-nitrocinnamylidene moiety, α,β-monoepoxides were also isolated as minor products. The structures of all new compounds and the stereochemistry of the monoepoxides and diepoxide diastereomers were established by NMR studies.

NMR spectroscopic elucidation of the structure and stereochemistry of tricyclic 3-styrylpyrazolines

Diastereomeric mixtures of tricyclic 3‐styrylpyrazolines have been prepared by the reaction of 3‐cynnamylidenechroman‐4‐ones and their 1‐thio analogs with hydrazine in hot acetic acid or propionic acid solutions. The diastereomeric mixtures were separated by column chromatography to obtain the pure diastereomers. The elucidation of their structure and stereochemistry and complete 1H and 13C assignments have been performed by a combination of various one‐ and two‐dimensional NMR experiments. Copyright