A new pathway for the preparation of biologically active 2 substituted 1,5-dihydrobenzo[e][1,2,4]oxadiazepines and related compounds by palladium-catalyzed cyclization of amidoximes with o-iodobenzyl bromide or 2-bromo-3-chloromethylpyridine

Abstract

This paper describes an efficient approach for the regioselective synthesis of new series of twenty 1-aryloxy(thio)acetyl and 1-(phenylamino)acetyl-substituted 5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazoles (3) in 34-96% yields from the cyclocondensation reaction of 4-alkoxy-4-alkyl-(aryl/heteroaryl)-1,1,1-trifluoroalk-3-en-2-ones with different substituted acetohydrazides. Dehydration reactions of 3, carried out in the presence of thionyl chloride, furnished two examples of aromatic 5-trifluoromethyl-1H-pyrazole derivatives, in 78-82% yields. From antimicrobial tests the fungi C. albicans proved to be particularly susceptible to the action of 1-(phenylamino)acetyl-substituted 3-alkyl-2-pyrazoline derivatives; however the first results are still weak when compared to standard drugs.

Elaboration of Benzoxadiazepine and Benzotriazocine Scaffolds

“…A N-arylation mechanism starting from the O-alkylated oxime intermediate, involving tautomeric shift before the reductive elimination step, has been suggested (scheme 14). [36][37][38] In 2014 Qian et al described a one-pot synthesis of a wide range of four-ring fused dibenzoxadiazepines, variously substituted by aryl-, heteroaryl or alkyl unit, in moderate to good yields (36-65%). Here the key step was a three-component reaction requiring 2-isocyanophenyl acetate, 2-amino-6-halogeno(het)aryl substrates and substituted aldehydes as precursors.…”

Assessment of DNA-binding affinity of cholinesterase reactivators and electrophoretic determination of their effect on topoisomerase I and II activity

“…Moreover, it was demonstrated that pyridinium oximes containing silicon are highly cytotoxic to human fibrosarcoma (HT-1080) and mouse hepatoma (MG-22A) cells. 25,26 Novel N-benzylpiperidin-4-one oxime molecules were screened for their anticancer activity against HeLa cells and exhibited an effective IC 50 value in the range 13.88-16.39 mM. 27 The ability of cholinesterase reactivators and inhibitors to relax topoisomerase I was studied by Janockova et al 28 and it was proved that cholinesterase inhibitors such as K524 (1,10-bis(quinolinium)-dec-1,10-diyl dibromide) or 7-MEOTA (9-amino-7-methoxy-1,2,3,4-tetrahydroacridine hydrochloride) inhibited this enzyme at a concentration of 30 mM; and selected cholinesterase reactivators such as K075 ((E)-1,4-bis(4-hydroxyiminomethyl pyridinium)-but-2-ene dibromide) exhibited partial weaker inhibition at a concentration of 60 mM.…”