Synthesis and antitumor activity of some new phthalimide analogues.

The reactive intermediate 1-(chloroalkyl)-1-aza-2-azoniaallene salts 3, which were prepared by treatment of the alpha,alpha'-dichloroazo derivatives 2 with SbCl5, underwent cycloaddition with the N-cyanoalkyl phthalimide compounds 4 and afforded the 1,2,4-triazolium salts 5. These salts rearranged spontaneously to the protonated 1,2,4-triazoles 6, followed by hydrolysis in situ to the 1,2,4-triazolo-alkyl-phthalimide compounds 7. The newly synthesized compounds were then evaluated for their antitumor activity in three cell lines.

Synthesis and antiviral activity of 1-[1,5-dialkyl-1H-1,2,4-triazol-3-yl)methyl]thymines.

Cycloaddition of the intermediates 2 with 1-(cyanomethyl)-thymine 3 furnished the 1,2,4-triazolium salts 4, which rearranged spontaneously to the protonated salts 5. Hydrolysis of 5, in situ, afforded the title compounds 6. Compounds 6a-c were screened against HIV-1 (IIIB), HIV-2 (ROD), and human cytomegalovirus (HMCV) and showed poor or no activity, respectively.

Synthesis of acyclic 6,7-dihaloquinolone nucleoside analogues as potential antibacterial and antiviral agents.

Reaction of the quinolone carboxylic acids 1 and 2 with (2-acetoxyethoxy)methyl chloride 3 in the presence of n-Bu4NI afforded the N-alkylated products 4 and 6, which could be deblocked to the free nucleoside analogues 5 and 7, respectively. The alkylated quinolone carboxylic acids 9 and 10 were obtained by condensation of I and 2 with 1,4-dichlorobut-2-ene 8 in the presence of NaH. Hydrolysis of 9 gave the alcohol 11. Similar treatment of 1 with 8 in the presence of K2CO3 at relatively high temperature furnished 12. Prolonged heating of the ester 13 with 8 in NaH/DMF afforded the conjugated-diene 15. Treatment of 1 and 2 with dimethyl acetylenedicarboxylate 16 furnished the pyrano[4,3-b]quinolones 17 and 18, respectively. Antibacterial and antiviral evaluations of the new products are reported.