Pyrazole, pyrazolone and enaminonitrile pyrazole derivatives: Synthesis, characterization and potential in corrosion inhibition and antimicrobial applications

In the present study we describe the syntheses and anticonvulsant activity evaluation of 5-phenyl-[1,2,4]triazolo[4,3-c]quinazolin-3-amine derivatives. Their anticonvulsant activity and neurotoxicity were evaluated by the maximal electroshock seizure test (MES) and the rotarod test, respectively. The majority of the compounds prepared were effective in the MES screens at a dose level of 100 mg/kg. Of these compounds, the most promising was compound 8h, which showed an ED(50) value of 27.4 mg/kg and a protective index (PI) value of 5.8. These values were superior to those provided by valproate (ED(50) and PI values of 272 and 1.6, respectively) in the MES test in mice. As well as its anti-MES efficacy, the potencies of compound 8h against seizures induced by pentylenetetrazole and thiosemicarbazide were also established, with the results suggesting that the GABAergic system-mediated mechanisms might be involved in its anticonvulsant activity.

Synthesis and Anticonvulsant Activity Evaluation of 5-Phenyl-[1,2,4]triazolo[4,3-c]quinazolin-3-amines

Determination of dissociation constant of some quinazoline derivatives at different temperatures in DMF–water medium

Annular tautomerism of 3(5)-aminopyrazoles containing a cyano, thiocyanato, or aryl substituent in the 4-position has been studied by 1H and 13C NMR in solution, cross-polarization and magic-angle spinning 13C NMR in the solid state, and ab initio quantum chemical calculations (B3LYP/6-31G**). The title compounds in the solid state exist as 3-amino tautomers. A rare case of slow (on the NMR time scale) annular prototropic tautomerism has been observed in DMSO-d
 6: signals of particular tautomers (3- and 5-aminopyrazoles) have been detected in the NMR spectra. 4-Cyano and 4-thiocyanato derivatives exist preferentially as 5-amino tautomers, whereas 4-methoxy analog is represented mainly by the 3-amino tautomers. Ab initio calculations (B3LYP/6-31G**) for the gas phase and DMSO solution (in terms of the polarizable continuum model) have shown increase of the relative stability of more polar 5-amino tautomer in going to DMSO.

Structure and tautomerism of 4-substituted 3(5)-aminopyrazoles in solution and in the solid state: NMR study and Ab initio calculations

The present work is concerned with the synthesis of some new compounds comprising different 2, 3-disubstituted 4(3 H) – quinazolinones as series 5- 7, 10- 13 , 15- 17 , 19 and 20 , 2, 3, 4- trisubstituted quinazolines as in series 8 and 9 and fused quinazolines as in 14 and 18 . The building block of these different compounds is the 3-amino-2-substituted quinazolin-4(3H)-ones 5 a- d. To study the effect of steric hindrance and positional isomerism on the antimicrobial activity; substitution in the 2 position of the quinazoline ring was accomplished by tolyl derivatives or naphthyl radicals. Also, the 2-chloro-N-(4-oxo-2-substituted-quinazolin-3(4 H)-yl) acetamido 15 a-d were synthesized and used as starting materials to prepare other new tricyclic derivatives 14 and 18 . In addition, these intermediates 15 a-d were reacted with various hydrazides of drugs like isoniazide, norfloxacin and ofloxacin to yield the biodynamic compounds 17 , 19 , and 20 . Furthermore, reaction of the chloroacetamido intermediates 15 a-d with potassium cyanate afforded compounds 16 a-d. The antimicrobial activity was tested for some new compounds against Gram positive and Gram negative microorganisms and the fungus Candida albicans. Additionally, minimum inhibitory concentration (MIC) was determined for nine compounds. Of these 10h, 14b, 15a were expressed as broad spectrum and 5a, 10b, 11a, 12a, 20a as narrow spectrum against variable microorganisms.

Design and synthesis of some quinazoline derivatives of anticipated antimicrobial activity

New substituted aroylhydrazones (4a-f) were synthesized from the acid hydrazide (3) and the corresponding aldehyde or aldose. 5-Amino-4-cyano-1H-pyrazole derivatives (6a-f) were prepared by the reaction of the aroylhydrazones (4a-f) with malononitrile. The synthesized compounds were tested for antimicrobial activity against various bacteria and fungi and showed moderate to high inhibition activities. Compounds incorporating a sugar moiety as well as a pyrazolyl ring in their structure displayed the highest antimicrobial activity.

Mohamed T. Abdel-Aal

Papers

Synthesis and antimicrobial activity of novel 5-amino-4-cyano-1H-pyrazole and quinazolin-4(3H)-one derivatives.