Synthesis and QSAR Study of (4-Oxo-3-aryl-3,4- dihydro-quinazolin-2-ylsulfanyl)-propionic Acid arylidene/aryl-ethylidene-hydrazides via Microwave Assisted Solvent Free Reations

In the present work, s-alkylated derivatives of thio-quinazolinone were obtained using Methyl 2-chloro propionate via a solvent-free microwaveassisted method. The alkylated thio quinazolinones were further sequentially condensed with hydrazine hydrate and different aromatic aldehydes to get the hydrazides, which were studied for QSAR. The synthesized compounds were subjected to a prediction of biological activities. A software application (PASS) was used for this purpose. . The relationship between structure and different biological activities was studied and the different derivatives were recommended for the screening of some specific activities like antituberculosic, anti-mycobacterial & HDL cholesterol increasing activities.


Introduction
In recent years the use of microwave irradiation in organic reactions is rapidly increasing because of the short reaction time, operational simplicity and formation of clean reaction products.Avoiding use of organic solvent during the reactions in organic synthesis leads to a clean, efficient and economical technology (green chemistry).It has been commonly employed as thermal energy source in various organic reactions 1 .The use of domestic microwave oven in this regard is now a well-established procedure in MORE 2 (microwave induced organic reaction enhancement) chemistry.It has been reported that the rate of variety of organic reactions such as Diels-Alder 3 , ene 4 , Claisen reaction 5 , oxidation 6 , reduction 7 , diacetylation 8 , deacetylation 9 , deoximation 10 , esterification 11 , hydrolysis of ester 12 , Doebner condensation 13 , Knoevenagel condensation 14 could be enhanced by microwave irradiation.Several workers have reported the alkylation of N-containing heterocycles.In this regard microwave (MW) activation have been successfully applied in the synthesis of such derivatives [15][16][17] .
Quinazoline derivatives are of special importance because of their versatile biological & pharmacological activities [18][19][20] , especially anti-inflammatory [21][22][23] , anti-convulsant 24 , hypnotic 25 , anthemintic 26 , hypotensive 27 , antibacterial 28 agents etc.In the present work, s-alkylated derivatives of thio-quinazolinone were obtained using Methyl 2-chloro propionate via a solvent-free microwave-assisted method.The alkylated thio quinazolinones were further sequentially condensed with hydrazine hydrate and different aromatic aldehydes to get the hydrazides, which were studied for QSAR.The synthesized compounds were subjected to a prediction of biological activities.A software application (PASS) was used for this purpose.The relationship between structure and different biological activities was studied and the different derivatives were recommended for the screening of some specific activities.

Experimental Section
All mps.were determined in open capillary tubes and are uncorrected.IR spectra were recorded in KBr on Shimadzu IR-437 spectrophotometer and PMR spectra in CDCl 3 and DMSO-d 6 on Perkin-Elmer R-32 spectrometer using TMS as an internal standard.The purity of the compounds was checked by TLC.Microwave irradiation was carried out in the domestic microwave oven by SHARP.
Similarly, the other compounds II-(b-g) were prepared and their purity was checked by TLC and the structures confirmed on the basis of IR and PMR spectral and elemental analysis data.

Results and Discussion
The compounds of the type (4-Oxo-3-aryl -3,4-dihydro-quinazolin-2-ylsulfanyl)-propionic acid (substituted-benzyledene)-hydrazide IV (a-g)(1-6) were studied for the predictions of their probabilities of being active [Pa] and inactive [Pi] for the selected activities such that the Pa>70% .A software application (PASS) was used for this purpose.The relationship between structure and different biological activities was studied.It was found that the 2-methy phenyl quinazolinones are expected to exhibit spectacular HDL Cholesterol Increasing activity, whereas the 3-chloro-phenyl and 4-chlorophenyl quinazolinone condensed with all the three substituted benzaldehydes are expected to exhibit spectacular HDL Cholesterol Increasing activity.Other 4-substituted phenyl derivatives are also expected to exhibit spectacular HDL Cholesterol Increasing activity.Hence these compounds are recommended for the screening of HDL Cholesterol Increasing activity.Similarly the derivatives of quinazolinones condensed with different aromatic ketones were when subjected to PASS, we found only one activity at Pa>70%.The derivatives with R 1 =2-Me are expected to exhibit spectacular HDL cholesterol increasing activity.Whereas the derivatives of quinazolinones condensed with 4-methyl substituted benzophenone were found to be more probably active as compared with those substituted with other groups.In the present scheme, unlike the similar acetic acid hydrazide derivatives of the quinazolinones, one cant draw a conclusion about the expected more activity for the quinanazolinone derivatives condensed with different aromatic ketones as compared to those with aldehydes.Hence these compounds were recommended for the screening of HDL Cholesterol Increasing activity.V-a 1 3320(phenolic OH),1720(cyclic amido), 1680(acyclic >C=O), 1620(>C=N).

Table 1 .
Physical and Analytical data of the compounds [II-(a-g)]

Table 3 .
General characteristics and elemental analysis data of the compounds [III-(a-g)]

Table 7 .
General characteristics and elemental analysis data of the compounds V-(a-c) (1-3