scholarly journals Safety and Antiviral Activity at 48 Weeks of Lopinavir/Ritonavir plus Nevirapine and 2 Nucleoside Reverse‐Transcriptase Inhibitors in Human Immunodeficiency Virus Type 1–Infected Protease Inhibitor–Experienced Patients

2002 ◽  
Vol 185 (5) ◽  
pp. 599-607 ◽  
Author(s):  
Constance A. Benson ◽  
Steven G. Deeks ◽  
Scott C. Brun ◽  
Roy M. Gulick ◽  
Joseph J. Eron ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Protease Inhibitor ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Immunodeficiency Virus

scholarly journals Preclinical Evaluation of GS-9160, a Novel Inhibitor of Human Immunodeficiency Virus Type 1 Integrase

2008 ◽  
Vol 53 (3) ◽  
pp. 1194-1203 ◽  
Author(s):  
Gregg S. Jones ◽  
Fang Yu ◽  
Ameneh Zeynalzadegan ◽  
Joseph Hesselgesser ◽  
Xiaowu Chen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Reverse Transcriptase Inhibitors ◽  
Single Mutant ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT GS-9160 is a novel and potent inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase (IN) that specifically targets the process of strand transfer. It is an authentic inhibitor of HIV-1 integration, since treatment of infected cells results in an elevation of two-long terminal repeat circles and a decrease of integration junctions. GS-9160 has potent and selective antiviral activity in primary human T lymphocytes producing a 50% effective concentration (EC50) of ∼2 nM, with a selectivity index (50% cytotoxic concentration/EC50) of ∼2,000. The antiviral potency of GS-9160 decreased by 6- to 10-fold in the presence of human serum. The antiviral activity of GS-9160 is synergistic in combination with representatives from three different classes of antiviral drugs, namely HIV-1 protease inhibitors, nonnucleoside reverse transcriptase inhibitors, and nucleotide reverse transcriptase inhibitors. Viral resistance selections performed with GS-9160 yielded a novel pattern of mutations within the catalytic core domain of IN; E92V emerged initially, followed by L74M. While E92V as a single mutant conferred 12-fold resistance against GS-9160, L74M had no effect as a single mutant. Together, these mutations conferred 67-fold resistance to GS-9160, indicating that L74M may potentiate the resistance caused by E92V. The pharmacokinetic profile of GS-9160 in healthy human volunteers revealed that once-daily dosing was not likely to achieve antiviral efficacy; hence, the clinical development of this compound was discontinued.

scholarly journals Indolylarylsulfones, a fascinating story of highly potent human immunodeficiency virus type 1 non-nucleoside reverse transcriptase inhibitors

2018 ◽  
Vol 26 ◽  
pp. 204020661775344 ◽  
Author(s):  
Valeria Famiglini ◽  
Romano Silvestri
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Drug Candidates ◽  
Immunodeficiency Virus ◽  
Nitrogen Coupling

Indolylarylsulfones are a potent class of human immunodeficiency virus type 1 non-nucleoside reverse transcriptase inhibitors. In this review, the structure activity relationship (SAR) studies to improve the profile of sulfone L-737,126 discovered by Merck AG have been analysed with focus on introduction of the 3′,5′-dimethyl groups at the 3-phenylsulfonyl moiety, the 2-hydroxyethyl tail at the indole-2-carboxamide nitrogen, coupling of the carboxamide nitrogen with one or two glycinamide and alaninamide units, a fluorine atom at position 4 of the indole ring and correlation between configuration of the asymmetric centre and linker length. IAS derivatives look like promising drug candidates for the treatment of AIDS and related infections in combination with other antiretroviral agents.

Sign in / Sign up

Export Citation Format

Share Document