Synthesis and antimicrobial activity of imidazo- and pyrimido[2,1-f]- theophyllines

Abstract

Heating of 8-aminotheophylline with methyl (Z)-2-benzoylamino-3- (dimethylamino)propenoate in acetic acid afforded in a one-pot synthesis a new pyrimido[2,1-f]theophylline derivative. Methylation of this by using CH 3I/NaH furnished in good yield the double methylated derivative. Furthermore, glycosidation of the former with 1-α-bromo-2,3,4,6-tetra-O- acetyl-d-glucose gave the β-glucoside derivative. Reaction of 8-aminotheophylline with [bis(methylthio)methylene]malonitrile, ethyl[bis(methylthio)methylene]cyanoacetate, 1,3-diphenylprop-2-en-1-one, 2-cyano-1,3-diphenylprop-2-en-1-one, 1-(4-nitrophenyl)-3-(dimethylamino)prop-2- ennitrile, 1-phenyl-3-(dimethylamino)prop-2-en-1-one, 2-substituted 3-aryl or heteroarylprop-2-ennitrile and ethyl(arylmethylene)cyanoacetate in N,N-dimethylformamide in the presence of anhydrous potassium carbonate afforded also the corresponding new derivatives of pyrimido-[2,1-f]theophylline. However, 8-aminotheophylline reacted in similar manner with 3-chloropentan-2,4-dione and 2-bromo-1-phenylethanone to give the corresponding imidazo[2,1-f]theophyllines. Furthermore, azo-coupling of one of these with 4-methylphenyldiazonium chloride was performed. The antimicrobial activity of the products has been evaluated. The structures of all new compounds obtained were established by their spectral analyses. © 2008 Springer-Verlag.