title: Structure-activity relationship studies on clinically relevant HIV-1 NNRTIs.
abstract: In addition to the nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs) and integrase inhibitors (INIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) have contributed significantly in the treatment of HIV-1 infections. More than 60 structurally different classes of compounds have been identified as NNRTIs, which are specifically inhibiting HIV-1 reverse transcriptase (RT). Five NNRTIs (nevirapine, delavirdine, efavirenz, etravirine and rilpivirine) have been approved by US Food and Drug Administration (FDA) for clinical use. The NNRTIs bind with a specific 'pocket' site of HIV-1 RT (allosteric site) that is closely associated with the NRTI binding site. Due to mutations of the amino acid residues surrounding the NNRTI-binding site, NNRTIs are notorious for rapidly eliciting resistance. Though, the emergence of resistant HIV strains can be circumvented if the NNRTIs are used either alone or in combination with NRTIs (AZT, 3TC, ddI, ddC, TVD or d4T) and PIs (Indinavir, nelfinavir, saquinavir, ritonavir and lopinavir etc.) as shown by both a decrease in plasma HIV-1 RNA levels and increased CD4 T-cells. Here we are going to discuss recent advances in structure activity relationship studies on nevirapine, delavirdine, efavirenz, etravirine, rilpivirine and 4-thiazolidinones (privileged scaffold) HIV-1 NNRTIs.
authors.affiliation: Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226001, India.
authors.forename: R K
authors.initials: RK
authors.lastname: Rawal
authors.forename: V
authors.initials: V
authors.lastname: Murugesan
authors.forename: S B
authors.initials: SB
authors.lastname: Katti
mesh_terms: D048588:Benzoxazines / Q000737:chemistry / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology; D006801:Humans; D010879:Piperazines / Q000737:chemistry / Q000627:therapeutic use; D011743:Pyrimidines / Q000737:chemistry / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000627:therapeutic use; D014227:Triazines / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D048588:Benzoxazines; D010879:Piperazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D013844:Thiazoles; D014227:Triazines; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; C030986:pyrimidine