Vigneshwaran Namasivayam1, Murugesan Vanangamudi2, Victor G Kramer3, Sonali Kurup4, Peng Zhan5, Xinyong Liu5, Jacob Kongsted6, Siddappa N Byrareddy7. 1. Pharmaceutical Institute, Pharmaceutical Chemistry II , University of Bonn , 53121 Bonn , Germany. 2. Department of Medicinal and Pharmaceutical Chemistry , Sree Vidyanikethan College of Pharmacy , Tirupathi , Andhra Pradesh 517102 , India. 3. Merck Canada Inc. , Kirkland , Quebec H9H 4M7 , Canada. 4. College of Pharmacy , Roosevelt University , Schaumburg , Illinois 60173 , United States. 5. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , 44 West Culture Road , Jinan 250012 , P.R. China. 6. Department of Physics, Chemistry and Pharmacy , University of Southern Denmark , DK-5230 , Odense M , Denmark. 7. Department of Pharmacology and Experimental Neuroscience , University of Nebraska Medical Center , Omaha 68198-5880 , United States.
Abstract
Human immunodeficiency virus (HIV) infection is now pandemic. Targeting HIV-1 reverse transcriptase (HIV-1 RT) has been considered as one of the most successful targets for the development of anti-HIV treatment. Among the HIV-1 RT inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have gained a definitive place due to their unique antiviral potency, high specificity, and low toxicity in antiretroviral combination therapies used to treat HIV. Until now, >50 structurally diverse classes of compounds have been reported as NNRTIs. Among them, six NNRTIs were approved for HIV-1 treatment, namely, nevirapine (NVP), delavirdine (DLV), efavirenz (EFV), etravirine (ETR), rilpivirine (RPV), and doravirine (DOR). In this perspective, we focus on the six NNRTIs and lessons learned from their journey through development to clinical studies. It demonstrates the obligatory need of understanding the physicochemical and biological principles (lead optimization), resistance mutations, synthesis, and clinical requirements for drugs.
class="Disease">Human immunodeficiency virus (HIV) infection is class="Chemical">now pandemic. Targeting n class="Species">HIV-1 reverse transcriptase (HIV-1 RT) has been considered as one of the most successful targets for the development of anti-HIV treatment. Among the HIV-1 RT inhibitors, non-nucleosidereverse transcriptase inhibitors (NNRTIs) have gained a definitive place due to their unique antiviral potency, high specificity, and low toxicity in antiretroviral combination therapies used to treat HIV. Until now, >50 structurally diverse classes of compounds have been reported as NNRTIs. Among them, six NNRTIs were approved for HIV-1 treatment, namely, nevirapine (NVP), delavirdine (DLV), efavirenz (EFV), etravirine (ETR), rilpivirine (RPV), and doravirine (DOR). In this perspective, we focus on the six NNRTIs and lessons learned from their journey through development to clinical studies. It demonstrates the obligatory need of understanding the physicochemical and biological principles (lead optimization), resistance mutations, synthesis, and clinical requirements for drugs.
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