Synthesis of isoxazole-containing sulfonamides with potent carbonic anhydrase II and VII inhibitory properties.

Two series of benzenesulfonamide containing isoxazole compounds were prepared by using conventional and microwave (MW) methods. 5-Amino-3-aryl-N-(4-sulfamoylphenyl)isoxazole-4-carboxamide derivatives were synthesized by the reaction of hydroxymoyl chlorides with 2-cyano-N-(4-sulfamoylphenyl)acetamide in the presence of triethylamine. The synthesized 5-amino isoxazoles were reacted with various benzoyl chlorides in order to obtain 5-amidoisoxazoles. The novel compounds were screened in vitro as inhibitors of four human (h) isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1): hCA I, hCA II, hCA IV and hCA VII. The derivatives of the first series were shown to possess excellent inhibitory activity against the cytosolic isoform hCA II, an antiglaucoma drug target, with KIs in the range of 0.5-49.3nM and hCA VII, a recently validated anti-neuropathic pain target with KIs in the range of 4.3-51.9nM.

Reaction of heterocyclic enamines with nitrile oxide and nitrilimine precursors.

Alkylidenepyrrolidines 1, 21, 24 and 26 undergo reactions with nitrile oxides and nitrilimines or their precursors to give a range of novel heterocyclic compounds. With alkylidenepyrrolidine ester 1, nitrolic acids give products in which the liberated nitrous acid reacts with the alkylidenepyrrolidine, followed by two cycloadditions to give adducts 3. In contrast, hydroximoyl chlorides give isoxazoles 10, presumably by cycloaddition/elimination. With hydrazonyl chlorides, simple acylation of the alkylidenepyrrolidine occurs to give compounds 17. With sulfonyl alkylidenepyrrolidines 24 and 26, cycloaddition onto the imine tautomer is the preferred pathway, with a stereoselective reaction taking place in the latter case.

Bis(3-phenyl-1,2,4-thiadiazole-5-thiolato)mercury(II).

The title compound, [Hg(C8H5N2S2)2], has crystallographic C2 symmetry. The Hg-S distance is 2.353 (2) A and the coordination geometry is linear, with an S-Hg-S angle of 179.77 (18) degrees. The exocyclic C-S single-bond distance is 1.749 (6) A, and intramolecular Hg...N distances of 2.857 (4) A exist, as well as secondary Hg...C and S...S contacts.