all the solvents and chemicals were purchased from merck , nice chemicals and sd fine chemicals .
melting points were determined by using melting point apparatus mp - ds tid 2000 v and the values were uncorrected .
reactions were monitored by thin layer chromatography ( tlc  methanol : acetone , 6 : 4 ) on pre - coated silica gel g plates using iodine vapor as visualizing agent .
ir spectra were recorded on jasco ft / ir-140 spectrophotometer by using kbr pellets technique .
pmr spectra were recorded using brucker ft - nmr-500 mhz spectrophotometer by using dmso as solvent and tms as internal standard .
the experimental protocol for the pharmacological screening on rats were done with an institutional animal ethics committee , k.m .
college of pharmacy , madurai , india ( reg no : 661/02/c / cpcsea ) .
2-acetyl benzimidazole ( 0.01 mol ) and appropriately substituted aromatic aldehydes ( 0.012 mol ) were mixed in ethanol ( 20 ml ) containing 10% aq .
koh ( 8 ml ) and magnetically stirred the solution constantly at room temperature for 10 h. the whole mixture was transferred into a 100 ml ice cold water and acidified with dil .
the solid formed was washed , filtered and dried , recrystallized from absolute ethanol . to a solution of ( 4a 
f ) ( 0.01 mol ) was suspended in 7 ml acetic acid . to this barbituric acid ( 0.01 mol )
the reaction progress was monitored by tlc ( methanol : acetone , 6 : 4 ) .
the crude product was filtered , washed with water and recrystallized from methanol . physical characterization of all the synthesized derivatives is shown in table 1 .
physical characterization and insilico screening of ( 5a - f ) 3230(nhstr),1693(c = o),1587 ( c = n ) .
hnmr(dmso - d6 ) ,  ppm9.1(1h , s , nhbenzimidazole ) , 8.0 - 8.4(2h , s , pyrimidinenh)6.4 - 8.1(11h , m,9arh,2ch = ch).m.s : m / z=359.21 ( m + 1 ) .
hnmr(dmso - d6 ) , ppm:8.9(1h , s , nhbenzimidazole),8.4 - 8.6(2h , s , pyrimidinenh)6.4 - 8.3(11h , m,9arh,2ch = ch).m.s : m / z=394.1 ( m + 2 ) 3239(nhstr),1681(c = o),1576(c
= n ) , hnmr(dmso - d6 ) ,  ppm:8.9(1h , s , nhbenzimidazole),8.4 - 8.6(2h , s , pyrimidinenh),6.4 - 8.3(10h , m,8arh,2ch = ch).3.3(3h , s , och3 ) . m.s :
hnmr(dmso - d6 ) ,  ppm:8.9(1h , s , nhbenzimidazole),8.5 - 8.7(2h , s , pyrimidinen),6.3 - 8.4(10h , m,8arh,2ch = ch).3.3(6h , s , n(ch3)2 m.s : m / z=402.56 ( m + 1 ) 3227(nhstr).1678(c = o),1569(c = n),1310(ar - no2 ) .
hnmr(dmso - d6),ppm:8.5(1h , s , nhbenzimidazole),8.2 - 8.4(2h , s , pyrimidinenh),6.4 - 8.4(10h , m,8arh,2ch = ch ) m.s : m / z=405.56 ( m + 2 ) 3379(aroh),3231(nhstr),1680(c = o),1562(c
hnmr(dmso - d6),ppm:9.1(1h , s , nhbenzimidazole),8.4 - 8.8(2h , s , pyrimidinenh)6.4 - 8.5(10h , m,8arh,2ch = ch),5.62(1h , s , aro - h ) m.s : m / z=375.65 ( m + 1 ) estimation of general biological potential for drug - like compounds on the basis of their structural formulae can be performed with a computer program pass ( prediction of activity spectra for substances ) that predicts more than 780 pharmacological effects .
all the structures of the derivatives were built by acd chemsketch version 12.0 and saved as mol format .
these can mol formats can be imported into the pass for prediction of the biological activity .
this program was based on a robust analysis of structure - activity relationships in a heterogeneous training set .
a biological spectrum for a substance is a list of biological activity types for which the probability to be revealed ( pa ) and not to be revealed ( pi ) values are independent and their values ranges from 0 to 1 .
the more is the pa value , the less is the probability of false positives in the set of compounds selected for study.[1315 ] all the titled derivatives predicted a biological activity of mucomembranous protector nature with a pa values more than 0.70 .
the study was carried out for four days after administration of the treated dose half hour after the rats were treated with aspirin 200 mg / kg .
this process was carried out for three days . on the third day after administration of drug ,
the rats were sacrificed four hours later by cervical dislocation and the esophagi were clamped , the stomach was exposed carefully , opened along the greater curvature , the luminal contents were removed , and the total volume of gastric secretion , total acidity , free acidity were estimated by titration method .
the percentage of ulcer inhibition was determined as follows : values are expressed as mean  sem , values were found by using one - way anova followed by newman keul 's multiple range tests [ table 2 ] .
2-acetyl benzimidazole ( 0.01 mol ) and appropriately substituted aromatic aldehydes ( 0.012 mol ) were mixed in ethanol ( 20 ml ) containing 10% aq .
koh ( 8 ml ) and magnetically stirred the solution constantly at room temperature for 10 h. the whole mixture was transferred into a 100 ml ice cold water and acidified with dil .
to a solution of ( 4a  f ) ( 0.01 mol ) was suspended in 7 ml acetic acid . to this barbituric acid ( 0.01 mol )
the reaction progress was monitored by tlc ( methanol : acetone , 6 : 4 ) .
physical characterization and insilico screening of ( 5a - f ) 3230(nhstr),1693(c = o),1587 ( c = n ) .
hnmr(dmso - d6 ) ,  ppm9.1(1h , s , nhbenzimidazole ) , 8.0 - 8.4(2h , s , pyrimidinenh)6.4 - 8.1(11h , m,9arh,2ch = ch).m.s : m / z=359.21 ( m + 1 ) .
hnmr(dmso - d6 ) , ppm:8.9(1h , s , nhbenzimidazole),8.4 - 8.6(2h , s , pyrimidinenh)6.4 - 8.3(11h , m,9arh,2ch = ch).m.s : m / z=394.1 ( m + 2 ) 3239(nhstr),1681(c = o),1576(c
= n ) , hnmr(dmso - d6 ) ,  ppm:8.9(1h , s , nhbenzimidazole),8.4 - 8.6(2h , s , pyrimidinenh),6.4 - 8.3(10h , m,8arh,2ch = ch).3.3(3h , s , och3 ) .
hnmr(dmso - d6 ) ,  ppm:8.9(1h , s , nhbenzimidazole),8.5 - 8.7(2h , s , pyrimidinen),6.3 - 8.4(10h , m,8arh,2ch = ch).3.3(6h , s , n(ch3)2 m.s : m / z=402.56 ( m + 1 ) 3227(nhstr).1678(c = o),1569(c = n),1310(ar - no2 ) .
hnmr(dmso - d6),ppm:8.5(1h , s , nhbenzimidazole),8.2 - 8.4(2h , s , pyrimidinenh),6.4 - 8.4(10h , m,8arh,2ch = ch ) m.s : m / z=405.56 ( m + 2 ) 3379(aroh),3231(nhstr),1680(c = o),1562(c
hnmr(dmso - d6),ppm:9.1(1h , s , nhbenzimidazole),8.4 - 8.8(2h , s , pyrimidinenh)6.4 - 8.5(10h , m,8arh,2ch = ch),5.62(1h , s , aro - h ) m.s : m / z=375.65 ( m + 1 )
hnmr(dmso - d6 ) ,  ppm9.1(1h , s , nhbenzimidazole ) , 8.0 - 8.4(2h , s , pyrimidinenh)6.4 - 8.1(11h , m,9arh,2ch = ch).m.s : m / z=359.21 ( m + 1 ) .
hnmr(dmso - d6 ) , ppm:8.9(1h , s , nhbenzimidazole),8.4 - 8.6(2h , s , pyrimidinenh)6.4 - 8.3(11h , m,9arh,2ch = ch).m.s : m / z=394.1 ( m + 2 )
3239(nhstr),1681(c = o),1576(c = n ) , hnmr(dmso - d6 ) ,  ppm:8.9(1h , s , nhbenzimidazole),8.4 - 8.6(2h , s , pyrimidinenh),6.4 - 8.3(10h , m,8arh,2ch = ch).3.3(3h , s , och3 ) .
hnmr(dmso - d6 ) ,  ppm:8.9(1h , s , nhbenzimidazole),8.5 - 8.7(2h , s , pyrimidinen),6.3 - 8.4(10h , m,8arh,2ch = ch).3.3(6h , s , n(ch3)2 m.s : m / z=402.56 ( m + 1 )
hnmr(dmso - d6),ppm:8.5(1h , s , nhbenzimidazole),8.2 - 8.4(2h , s , pyrimidinenh),6.4 - 8.4(10h , m,8arh,2ch = ch ) m.s : m / z=405.56 ( m + 2 )
hnmr(dmso - d6),ppm:9.1(1h , s , nhbenzimidazole),8.4 - 8.8(2h , s , pyrimidinenh)6.4 - 8.5(10h , m,8arh,2ch = ch),5.62(1h , s , aro - h ) m.s : m / z=375.65 ( m + 1 )
estimation of general biological potential for drug - like compounds on the basis of their structural formulae can be performed with a computer program pass ( prediction of activity spectra for substances ) that predicts more than 780 pharmacological effects .
all the structures of the derivatives were built by acd chemsketch version 12.0 and saved as mol format .
these can mol formats can be imported into the pass for prediction of the biological activity .
this program was based on a robust analysis of structure - activity relationships in a heterogeneous training set .
a biological spectrum for a substance is a list of biological activity types for which the probability to be revealed ( pa ) and not to be revealed ( pi ) values are independent and their values ranges from 0 to 1 .
the more is the pa value , the less is the probability of false positives in the set of compounds selected for study.[1315 ] all the titled derivatives predicted a biological activity of mucomembranous protector nature with a pa values more than 0.70 .
the study was carried out for four days after administration of the treated dose half hour after the rats were treated with aspirin 200 mg / kg .
this process was carried out for three days . on the third day after administration of drug ,
the rats were sacrificed four hours later by cervical dislocation and the esophagi were clamped , the stomach was exposed carefully , opened along the greater curvature , the luminal contents were removed , and the total volume of gastric secretion , total acidity , free acidity were estimated by titration method . the ulcer index was calculated according to the method of ganguly and bhatnagar .
the percentage of ulcer inhibition was determined as follows : values are expressed as mean  sem , values were found by using one - way anova followed by newman keul 's multiple range tests [ table 2 ] .
the present study described a knoevenagel condensation between a benzimidazole chalcone and barbituric acid by using experimental protocol as shown in figure 1 .
the structures of all the final derivatives were established on the basis of spectral analysis .
ir spectrum of the 5-[(2e)-1-(1h - benzimidazol-2-yl)-3-phenylprop-2-en-1-ylidene ] pyrimidine-2,4,6 ( 1h , 3h , 5h)-trione 5b showed a strong absorption band at 3232 cm corresponding to benzimidazole nh and absorption at 2910 and 2878 cm corresponding to pyrimidine nh / nh . a sharp absorption at 1678 cm corresponds to carbonyl stretching and 771 cm due to aryl chloride .
the hnmr spectra showed the singlet peak at  8.4 , and  8.6 was assigned to pyrimidine nh / nh . the singlet peak was at  8.9 corresponding to benzimidazole nh .
the doublet for vicinal protons has been seen along with the aromatic multiplet between  6.4 and 8.3 ppm .
mass spectrum of compound 5b revealed the molecular ion peak [ m+2 ] at m / z 394 corresponding to the molecular mass of the compound .
mass fragmentation pattern of 5b gave a base peak of m / z 58 which corresponds to the molecular formula of ch2n2o .
this splitting of the urea fragment from the 5b also made full agreement with the structure of final barbitone moiety .
scheme of synthetic route of the titled compounds the pass program predicted the mucomembranous protector nature probabilities 5-[(2e)-1-(1h - benzimidazol-2-yl)-3-substituted phenylprop-2-en-1-ylidene ] pyrimidine-2 , 4 , 6 ( 1h , 3h , 5h)-triones ( 5a  f ) showing the following rank order 5d > 5b > 5c > 5a > 5e > 5f .
it is important to note that compounds 5d , 5b and 5c showed a percentage protection of ( 69.58 , 69.56 and 67.17 at a dose of 50 mg / kg b.w . ) when compared to standard omeprazole ( 77.37% , 2 mg / kg b.w . ) .
this suggested a good correlation between the predicted and observed activity score in the final candidates .
administration of 200 mg / kg asa suspension intragastrically consistently caused hemorrhagic lesions in the mucosa of the glandular stomach , indicating true ulcer formation as stated in histological findings .
the stomach specimen of aspirin - treated rats was characterized by complete disruption of protective mucosal layer [ figure 2 ] .
the tissue of aspirin - treated rats had shown that some epithelial cells in the ulcer margin had proliferated and migrated over and into the ulcer crater , which was strongly infiltrated by inflammatory cells , fibroblasts and endothelial cells indicating complete disruption of gastric epithelial layer .
scanning of stomach specimens using electron microscope revealed that in the rats treated with omeprazole , 5b and 5d [ figures 35 ] , there was no injury observed in stomach mucosa , which is identical to that of the control animal [ figure 6 ] .
the present study described a knoevenagel condensation between a benzimidazole chalcone and barbituric acid by using experimental protocol as shown in figure 1 .
the structures of all the final derivatives were established on the basis of spectral analysis .
ir spectrum of the 5-[(2e)-1-(1h - benzimidazol-2-yl)-3-phenylprop-2-en-1-ylidene ] pyrimidine-2,4,6 ( 1h , 3h , 5h)-trione 5b showed a strong absorption band at 3232 cm corresponding to benzimidazole nh and absorption at 2910 and 2878 cm corresponding to pyrimidine nh / nh . a sharp absorption at 1678 cm corresponds to carbonyl stretching and 771 cm due to aryl chloride .
the hnmr spectra showed the singlet peak at  8.4 , and  8.6 was assigned to pyrimidine nh / nh . the singlet peak was at  8.9 corresponding to benzimidazole nh .
the doublet for vicinal protons has been seen along with the aromatic multiplet between  6.4 and 8.3 ppm .
mass spectrum of compound 5b revealed the molecular ion peak [ m+2 ] at m / z 394 corresponding to the molecular mass of the compound .
mass fragmentation pattern of 5b gave a base peak of m / z 58 which corresponds to the molecular formula of ch2n2o .
this splitting of the urea fragment from the 5b also made full agreement with the structure of final barbitone moiety .
the pass program predicted the mucomembranous protector nature probabilities 5-[(2e)-1-(1h - benzimidazol-2-yl)-3-substituted phenylprop-2-en-1-ylidene ] pyrimidine-2 , 4 , 6 ( 1h , 3h , 5h)-triones ( 5a  f ) showing the following rank order 5d > 5b > 5c > 5a > 5e > 5f .
it is important to note that compounds 5d , 5b and 5c showed a percentage protection of ( 69.58 , 69.56 and 67.17 at a dose of 50 mg / kg b.w . ) when compared to standard omeprazole ( 77.37% , 2 mg / kg b.w . ) . this suggested a good correlation between the predicted and observed activity score in the final candidates
administration of 200 mg / kg asa suspension intragastrically consistently caused hemorrhagic lesions in the mucosa of the glandular stomach , indicating true ulcer formation as stated in histological findings .
the stomach specimen of aspirin - treated rats was characterized by complete disruption of protective mucosal layer [ figure 2 ] .
the tissue of aspirin - treated rats had shown that some epithelial cells in the ulcer margin had proliferated and migrated over and into the ulcer crater , which was strongly infiltrated by inflammatory cells , fibroblasts and endothelial cells indicating complete disruption of gastric epithelial layer .
scanning of stomach specimens using electron microscope revealed that in the rats treated with omeprazole , 5b and 5d [ figures 35 ] , there was no injury observed in stomach mucosa , which is identical to that of the control animal [ figure 6 ] .
in conclusion , a series of some novel 5-[(2e)-1-(1h - benzimidazol-2-yl)-3-substituted phenylprop-2-en-1-ylidene ] pyrimidine-2 , 4 , 6 ( 1h , 3h , 5h)-triones were synthesized .
we also demonstrated that most of the titled compounds showed moderate in vivo antiulcer activity but all the derivatives exhibited a good mucomembranous protector .
the study has also shown an increase probability of compounds to be biologically active if they are selected on the basis of pass prediction .
 purpose : the present paper demonstrates the utility of pass computer - aided program and makes a clear comparison of predicted and observed pharmacological properties of some novel 5-[(2e)-1-(1h - benzimidazol-2-yl)-3-substituted phenylprop-2-en-1-ylidene ] pyrimidine-2 , 4 , 6 ( 1h , 3h , 5h)-triones ( 5a  f).materials and methods : the synthesis of the titled derivatives were achieved by the reaction between 2e)-1-(1h - benzimidazol-2-yl)-3-phenylprop-2-en-1-ones ( 4a  f ) and barbituric acid in the presence of catalytic amount of acetic acid medium . 
 all the final structures were assigned on the basis of ir , 1hnmr and mass spectra analysis . 
 all the newly synthesized compounds were screened for their antiulcer activity in the pylorus - ligated rats.results:compounds 5b , 5e and 5c showed a percentage protection of ( 69.58 , 69.56 and 67.17 at a dose of 50 mg / kg b.w . ) when compared to standard omeprazole ( 77.37% , 2 mg / kg b.w.).conclusion : scanning of stomach specimens using electron microscope revealed that the mice treated with standard and synthetic derivatives had no injury observed in stomach mucosa , which is identical to that of the control animal . 