ACTIVITY OF A NOVEL QUINOXALINE DERIVATIVE AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE AND VIRAL REPLICATION

S-2720 3-dimethyl-4-(isopropenyloxycarbonyl)-3,4-dihydroq uinoxalin-2( 1H)-thione!, a quinoxaline derivative, was found to be a very potent i nhibitor of both human immunodeficiency virus type 1 reverse transcrip tase (HIV-1 RT) activity and HIV-1 replication in tissue culture. Like other nonnucleoside RT inhibitors, S-2720 does not affect the HIV-2 R T. A S-2720-resistant virus was selected and shown to possess a mutati on within the RT-coding region that has not previously been described. Notably, this mutation gives rise to a dramatic decrease in enzyme ac tivity. S-2720, therefore, belongs to a new class of RT inhibitors tha t bind differently to the RT than other known nonnucleoside RT inhibit ors. As no toxic effects were observed with S-2720 in mice, these quin oxaline derivatives deserve further evaluation to prove their potency as possible therapeutic agents for HIV-1 infection.