2016
DOI: 10.1021/acs.jmedchem.5b01430
|View full text |Cite
|
Sign up to set email alerts
|

Discovery of the Aryl-phospho-indole IDX899, a Highly Potent Anti-HIV Non-nucleoside Reverse Transcriptase Inhibitor

Abstract: Here, we describe the design, synthesis, biological evaluation, and identification of a clinical candidate non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a novel aryl-phospho-indole (APhI) scaffold. NNRTIs are recommended components of highly active antiretroviral therapy (HAART) for the treatment of HIV-1. Since a major problem associated with NNRTI treatment is the emergence of drug resistant virus, this work focused on optimization of the APhI against clinically relevant HIV-1 Y181C and K103N… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

0
33
0

Year Published

2016
2016
2024
2024

Publication Types

Select...
8
1

Relationship

0
9

Authors

Journals

citations
Cited by 61 publications
(33 citation statements)
references
References 19 publications
0
33
0
Order By: Relevance
“…In medical science, indole based therapeutic drugs possess valuable biologic activities such as anti-HIV (Human immunodeficiency virus), antimicrobial, anti-malarial, antiviral, anti-fungal, antileishmanial, anti-oxidant, and anti-tubercular Fig. 1B [26][27][28][29][30][31][32][33] . Indole is a principal structural molecule which is explained as a privileged scaffold.…”
Section: Fig 1: (A) Discovery Of Indole (B) Pharmacological Profilementioning
confidence: 99%
“…In medical science, indole based therapeutic drugs possess valuable biologic activities such as anti-HIV (Human immunodeficiency virus), antimicrobial, anti-malarial, antiviral, anti-fungal, antileishmanial, anti-oxidant, and anti-tubercular Fig. 1B [26][27][28][29][30][31][32][33] . Indole is a principal structural molecule which is explained as a privileged scaffold.…”
Section: Fig 1: (A) Discovery Of Indole (B) Pharmacological Profilementioning
confidence: 99%
“…Recently,A lexandre and co-workers reportedad etailed procedure of identifying aryl-phospho-indole (IDX899)a sahighly potent NNRTI against the most prevalent mutantstrains K103N and Y181C and the double-mutant strain RES056. [66] The structural modification of the lead compound 101 resulted in the following facts about SARs:M ost of the mono-substituted phenyl-phosphino indoles were highly active against the wildtype HIV-1 strain. To be active against mutants trains, long lipophilic substituents were neededt ob ei ncorporated into the structure.…”
Section: -Chloro-3-(benzenesulfonyl)indole-2-carboxamide (L-737126;mentioning
confidence: 99%
“…In February 2009 it was licensed to GlaxoSmithKline and its name was changed to fosdevirine/GSK2248761. 76 In phase I clinical trials increased CD4+ cell counts in treatment-naïve patients infected with HIV-1 77 , 78 ( Chart 8 ).…”
Section: Arylphosphoindoles Idenix Laboratoriesmentioning
confidence: 99%