QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP (QSAR) STUDIES ON 5-CYANO, N1, 6-DISUBSTITUTED, 2-THIOURACIL DERIVATIVES AS CENTRAL NERVOUS SYSTEM DEPRESSANTS

Quantitative structure activity relationship (QSAR) studies of twenty four 5-cyano, N1, 6-disubstituted, 2-thiouracil derivatives were performed for their central nervous system (CNS) depressant (locomotor) activity using VlifeMDS3.5 software. Partial least square (PLS) linear regression analysis coupled with stepwise variable selection method was applied to derive QSAR models which were further validated for statistical significance and predictive ability by internal and external validation. The best QSAR model was selected, having correlation coefficient r 2 = 0.9014 and cross validated squared correlation coefficient q 2 = 0.8120 with external predictive ability of pred_r 2 = 0.6692. The QSAR model indicated that the vdWSurfaceArea (van der Waals surface area of the molecule), dipole moment, YcompDipole (y component of the dipole moment) and T_2_F_1 (count of number of double bounded atoms (i.e. any double bonded atom, T_2) separated from fluorine atom by 1 bond in a molecule) were the important determinants for CNS depressant (locomotor) activity

Multiple Linear Regression Study of 2,4-Disubstituted 1,5- Benzodiazepine as Potential Antiinfectives: 2,4-Disubstituted 1,5-Benzodiazepine as Potential Antiinfectives

This paper describes 3D-QSAR analysis and biological evaluation of 1,5-benzodiazepine analogues. Benzodiazepine nucleus with its simple structure gives a good opportunity for further modification regarding an increase of its antimicrobial activity. We synthesized a series of benzodiazepine analogues from condensation of various chalcones and halo substituted o-phenelynene diamines. All compounds were assayed in vitro against, E. coli, P. aeruginosa, S. aureus. The models were generated on the Vlife MDS 3.5; selected models showed a correlation coefficient (r2) above 0.9 with cross-validated correlation coefficient (q2) above 0.8, respectively, for all the selected organisms. The 3D-QSAR models generated were externally validated for all models using a test set of 6 molecules for which the predictive r2 (r2-pred) was found to be above 0.45. The results of 3D-QSAR indicate that contours can be used to design some potent antibacterial agents

IMPROVED SYNTHESIS OF SUBSTITUTED PYRIMIDIN-2-ONE DERIVATIVES USING MICROWAVE AND ULTRASOUND IRRADIATION

ABSTRACT Various substituted 4-oxo-2-thioxo tetrahydropyrimidine, 2-oxo dihydropyrimidine, 3,6-disubstituted and 4,5-disubstituted tetrahydropyrimidin-2-one derivatives containing different functional groups have been synthesized under microwave and ultrasound irradiation. The 3,6-disubstituted derivatives were prepared by reacting substituted pyrimidine derivatives synthesized under ultrasound irridation, with ethybromoacetate and product formed was converted to respective hydrazide derivatives, which were further condensed with various aromatic aldehydes. The 4,5-disubstituted tetrahydropyrimidines derivatives were synthesized simply by reacting substituted pyrimidine derivatives synthesized using modified biginelli reaction with various aromatic amines. The IR, 1 H NMR and mass spectral data confirmed the structure of the newly synthesized compounds. Keywords: Biginelli reaction, pyrimidine, Microwave, Ultrasound. INTRODUCTION Pyrimidine is a parent group of various heterocyclic compounds, which have attracted attention for long time. Pyrimidine derivatives play a vital role in many biological processes, the ring system being present in nucleic acids, several vitamins and coenzymes, uric acid and other purines. Uracil, thymine, and cytosine are three of the six bases found in the nucleotides, which contain pyrimidine ring. It is evident from the literature that pyrimidine derivatives have been found to have various pharmacological activities. Pyrimidine ring is the backbone of several calcium channel blocker[1], antibacterial[2], antifungal Step-I:Synthesis of 5-carbonitrile-6-aryl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine:[10 ] A mixture of ethyl cyanoacetate (0.01 mol), an aldehyde (0.01 mol) and thiourea (0.01 mol) in ethanol (20 ml) containing potassium carbonate (0.01 mol) was refluxed for 5 h. The potassium salt of product, which is precipitated during reaction, was collected and washed with ethanol and tetrahydrofuran. The crude salt was stirred in water at approximately 80° C; stirring was continued until the clear solution is obtained. After cooling the solution was acidify by acetic acid, and stirring was continued for 30 min. The deposited crystals thus formed were collected and washed well with water and dried in air. Recrystallization from acetic acid gave pure product. Desai Sujit Arun et al