Cycloaddition reaction of 8-diazotheophylline with some dipolarophiles: Facile synthesis of new derivatives of 1,2,4-triazino[3,4-<i>f</i>]purine

1064-1067[4+2] Cycloaddition of 8-diazotheophylline 2 with dipolarophiles 3-9 affords the corresponding new 1,2,4-triazino[3,4-ƒ]theophyllines 10-16 by refluxing in chloroform

Synthesis of new bis-heteroaryl thiohydrazonates and their <i style="">in situ</i> rearrangement

176-179Reaction of 3, 3'-bis(4-phenyl-1, 2, 4-triazole-5-thione) 1 with hydrazonoyl halides 2 in ethanol in the presence of sodium ethoxide affords directly the thiohydrazides 4, via in situ rearrangement of the initially formed thiohydrazonate esters 3. The involvement of the latter was evidenced by an alternate synthesis of 4

ORIENTAL JOURNAL OF CHEMISTRY Tandem Reactions Using Nitrile Imines: Synthesis of Some Novel Heterocyclic Compounds with Expected Biological Activity

ABSTRACT New functionalized 7,9-dimethylpyrimido [4,5-d

Synthesis and tautomeric structure of 7-arylhydrazono-7H-[1,2,4]triazolo[3,4-b]-[1,3,4]thiadiazines

Two synthetic approaches were developed for the title compounds 8a-g via coupling of diazotized anilines with 7-acetyl-6-methyl-3-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine 7, and reaction of N-aryl 2-oxopropanehydrazonoyl chlorides 9 with 4-omino-3-mercapto-5-phenyl-1,2,4-triazole 1. The tautomeric structures of 8 were elucidated by their spectral analyses and correlation of their acid dissociation constants with Hammett equation

Procatalytic Ligand Strain. Ionization and Perturbation of 8-Nitroxanthine at the Urate Oxidase Active Site

The binding of the inhibitor 8-nitroxanthine to urate oxidase has been investigated by Raman and UV−visible absorption spectroscopy. The absorption maximum of 8-nitroxanthine shifts from 380 to 400 nm upon binding to the enzyme, demonstrating that the electronic structure of the ligand is perturbed. It has been proposed that oxidation of the substrate urate by urate oxidase is facilitated by formation of the substrate dianion at the enzyme active site, and Raman spectra of urate oxidase-bound 8-nitroxanthine suggest that both the dianionic and monoanionic forms of the ligand are bound to the enzyme under conditions where in solution the monoanion is present exclusively. The C4−C5 stretching frequency appears as a relatively isolated vibrational mode in 8-nitroxanthine whose frequency shifts according to the protonation state of the purine ring. Identification of the C4−C5 stretching mode was confirmed using [4-13C]-8-nitroxanthine and ab initio calculation of the vibrational modes. Two peaks corresponding to the C4−C5 stretching mode were evident in spectra of enzyme-bound 8-nitroxanthine, at 1541 and 1486 cm-1. The higher frequency peak was assigned to monoanionic 8-nitroxanthine, and the low-frequency peak was assigned to dianionic 8-nitroxanthine. The C4−C5 stretching frequency for free monoanionic 8-nitroxanthine was at 1545 cm-1, indicating that the enzyme polarizes that bond when the ligand is bound. The C4−C5 stretching frequency in dianionic 8-nitroxanthine is also shifted by 4 cm-1 to lower frequency upon binding. For 8-nitroxanthine free in solution, the C4−C5 stretching frequency shifts to lower frequency upon deprotonation, and the absorption maximum in the UV−visible spectrum shifts to higher wavelength. The spectral shifts observed upon binding of 8-nitroxanthine to urate oxidase are consistent with increased anionic character of the ligand, which is expected to promote catalysis in the reaction with the natural substrate urate. In the Raman spectra of 8-nitroxanthine bound to the F179A, F179Y, and K9M mutant proteins, the C4−C5 stretching frequency was not perturbed from its position for the unbound ligand. Both Vmax and V/K were decreased in the mutant enzymes, demonstrating a correlation between the interaction that perturbs the C4−C5 stretching frequency and the catalytic activity of the enzyme. It is suggested that hydrogen-bonding interactions that lead to precise positioning and deprotonation of the substrate are perturbed by the mutations