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The Journey of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from Lab to Clinic.

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Namasivayam V,Vanangamudi M,Kramer VG,Kurup S,Zhan P,Liu X,Kongsted J,Byrareddy SN

doi

10.1021/acs.jmedchem.8b00843

subject

Has Abstract

pub_date

2019-05-23 00:00:00

pages

4851-4883

issue

10

eissn

0022-2623

issn

1520-4804

journal_volume

62

pub_type

杂志文章

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