Development of diarylpyrimidine derivatives (& other heterocycles) as HIV-1 and WTRT inhibitors

Reverse transcriptase (RT) is an enzyme encoded by the genetic material of retroviruses. Viruses such as HIV and hepatitis B employ an enzyme reverse transcriptase (RT) to generate complementary DNA from the RNA template during reverse transcription. Thus, viruses replicate their genomes and proliferate within the host genome. In particular, researchers are concerned about the pathogenic viruses that cause numerous diseases through this mechanism. The retroviruses that cause diseases in humans include human immunodeficiency virus (HIV), which causes AIDS, and human T-cell lymphotropic virus I (HTLV-1), which causes leukemia. HIV has been the most devastating health problem for decades. The number of recorded HIV cases was found to be approximately 39 million worldwide in 2022. Acquired immune deficiency syndrome (AIDS), most devastating disease caused by HIV-1 needs potent antiretroviral therapy for treatment. Among the effective treatments for AIDS, NNRTIs are key drugs in highly active antiretroviral therapy (HAART). Heterocyclic small molecules play an important role in drug discovery for treatment of HIV-1 infection. Particularly, diarylpyrimidines class of drugs have shown promising activity. In this review, anti-HIV-1 activity and RT inhibitory activity of heterocycle small molecules focusing mostly on diarylpyrimidines was discussed. Furthermore, structure-activity relationship was discussed emphasizing most potent molecules.