Synthesis and antibacterial activity of substituted 4-arylaminopyrimido[5,4-c]cinnolines.

A series of 4-arylamino pyrimido[5,4-c]cinnolines was synthesized and evaluated for antibacterial activity by serial 2-fold dilution technique. Several compounds showed significant activity. Amongst them 7-methyl-4-[(p-methyl phenyl) amino] pyrimido [5,4-c] cinnoline (2f) was the most active against Gram positive bacteria.

Synthesis of 7-substituted-4-(3',4',5'-trisubstituted-1-pyrazolyl)pyramido-[5,4-c] cinnolines and their anti-inflammatory activities.

Eight title compounds were synthesised from substituted anelines. All compounds were tested for inhibition of bovine serum albumin denaturation. Few selected compounds were studied for their ability to provide protection against carrageenin-induced edema in rat paw and to inhibit denaturation of bovine serum albumin in an attempt to elucidate their cellular mechanism of action. There was no relationship between anti-inflammatory activity of 7-substituted-4-(3',4',5'-trisubstituted-1-pyrazolyl)pyrimido[5,4- c] cinnolines and their bovine serum albumin denaturation effectiveness.

Anti-inflammatory activity of substituted 1,3,4-oxadiazoles.

Various 5-[[(acetamidophen-4-yl)oxy]methyl]-2-(p-substituted phenylamino)-1,3,4-oxadiazoles (4a-4d) were synthesized by cyclization of the corresponding N1-[[(acetamidophen-4-yl)oxy]acetyl]- N4-(p-substituted phenylamino)-3-thiosemicarbazides (3a-3d). All four of the thiosemicarbazides [250 mg/kg, orally (p.o.)] and the corresponding oxadiazoles (250 mg, p.o.) possessed anti-inflammatory activity. In the Carrageenan-induced edema test in rat paw, the activity ranged from 28 to 47% for 3a-3d and 44 to 63% for 4a-4d, with indomethacin (10 mg/kg, p.o.), used as the standard reference drug, showing 88.5% protection. The compounds (1 mM) were also tested for the inhibition of bovine serum albumin denaturation, and this activity ranged from 27 to 68%. No correlation was seen between the anti-inflammatory activity of 3a-4d and the inhibition of denaturation of bovine serum albumin. The low toxicity of these compounds was reflected by their high approximate 50% lethal dose (LD50) values, ranging from 2000 to 2500 mg/kg.

Inhibition of albumin denaturation and anti-inflammatory activity of acetamido [(phenyl-4'-yl)-oxymethyl)]2-(p-substituted phenylamino)-1,2,4-triazoles and -1,3,4-thiadiazoles.

Acetamido [(phenyl-4'-yl)-oxymethyl)]-2-(p-substituted-phenylamino)-1,2,4-tr iazoles (4a-4d) and 1,3,4-thiadiazoles (5a-5d) inhibited the thermal denaturation of bovine serum albumin. As protein denaturation is implicated in inflammation, some compounds which showed good inhibition of denaturation were tested in vivo for anti-inflammatory activity by carrageenan induced edema in the rat paw. Although there was no complete correlation, compounds which showed good inhibition of denaturation also showed significant anti-inflammatory activity.

Synthesis and anti-inflammatory activity of fluorinated phenyl styryl ketones and N-phenyl-5-substituted aryl-3-p-(fluorophenyl) pyrazolins and pyrazoles.

Various N-phenyl-5-substituted aryl-3-p-(fluorophenyl) pyrazolins and pyrazoles were synthesized by cyclization of the corresponding 4-(fluorophenyl) styryl and 4-(fluorophenyl) dibromostyryl ketones. These compounds were characterized by elemental analysis and UV, infrared, and nuclear magnetic spectral data. All substituted p-(fluorophenyl) styryl ketones [250 mg/kg orally (po)] possessed anti-inflammatory activity, as reflected by their ability to provide protection (51-70%) against carrageenin-induced edema in rat paw. Indomethacin (10 mg/kg, po) and dehydrozingerone (70 mg/kg, po), used as standard reference drugs, provided 97 and 60% protection, respectively. All compounds (0.20 mM) showed ability to denature bovine serum albumin, as observed in in vitro inhibition studies. Inhibition ranged from 7 to 59% for substituted p-(fluorophenyl) styryl ketones and from 12 to 21% for pyrazoles. No correlation was found between the anti-inflammatory activity of p-(fluorophenyl) styryl ketones or substituted pyrazoles and their effectiveness at inhibiting bovine serum albumin denaturation. The low toxicity of p-(fluorophenyl) styryl ketones was reflected by the dose that was lethal in 50% of the cases tested (2000-2500 mg/kg).

Synthesis and antimicrobial and anti-inflammatory activities of substituted 2-mercapto-3-(N-aryl)pyrimido[5,4-c]cinnolin-4-(3H)-ones.

Ten new substituted 2-mercapto-3-(N-aryl)pyrimido[5,4-c]cinnolin-4- (3H)-ones (4) were prepared by refluxing substituted 4-aminocinnolin-3-carboxylic acid (3) with substituted arylisothiocyanate in anhydrous pyridine. These derivatives were evaluated for their antimicrobial and anti-inflammatory activities. Some of the title compounds possess potent antimicrobial activity.