N-[2-(4-methylphenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea as a potent inhibitor of NNRTI-resistant and multidrug-resistant human immunodeficiency virus type 1.
Abstract: Notably, HI-244 was 20 times more effective than trovirdine against the multidrug-resistant HIV-1 strain RT-MDR with a V106A mutation (as well as additional mutations involving the RT residues 74V, 41L and 215Y) and seven times more potent than trovirdine against the NNRTI-resistant HIV-1 strain A17 with a Y181C mutation.
"Synthesis and evaluation of ""AZT-HEPT"", ""AZT-pyridinone"", and ""ddC-HEPT"" conjugates as inhibitors of HIV reverse transcriptase."
PMID: 10821705
2000
Journal of medicinal chemistry
Abstract: In marked contrast, the ddC-HEPT molecule 26 displayed the same potency (EC(50) = 0.45 microM) against HIV-1 (wild type and the Y181C nevirapine-resistant strain) and HIV-2 in cell culture.
Abstract: The (N-3 and C-5)AZT-HEPT conjugates 15, 22, and 23 displayed 2-5 microM anti-HIV activity, but they had no effect on the replication of HIV-2 or the HIV-1 strain with the Y181C mutation.
Efavirenz- and adefovir dipivoxil-based salvage therapy in highly treatment-experienced patients: clinical and genotypic predictors of virologic response.
PMID: 10839657
2000
Journal of acquired immune deficiency syndromes (1999)
Abstract: Patients with Y181C or G190A single mutations had an initial greater magnitude of viral load suppression than those with K103N, but this advantage was short lived.
Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase.
Abstract: Using Monte Carlo simulations, both free energy perturbation and linear response calculations were carried out for the transformation of wild-type RT to two key mutants, Y181C and L100I.
Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy.
PMID: 10952598
2000
Antimicrobial agents and chemotherapy
Abstract: V106A, Y181C, and Y188C mutations, which have been associated with high levels of resistance to other NNRTIs, were rare in the patient samples in this study, both before and after exposure to efavirenz.
Mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors demonstrate altered rates of RNase H cleavage that correlate with HIV-1 replication fitness in cell culture.
Abstract: In contrast, the Y181C reverse transcriptase demonstrated a selective acceleration of the secondary RNase H cleavage step during both modes of RNase H cleavage.
Abstract: Of the NNRTI-resistant mutants, V179D was more fit than Y181C, and both of these mutants were more fit than V106A, which demonstrated the greatest reduction in RNase H cleavage.
Abstract: Three mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (V106A, V179D, and Y181C), which occur in clinical isolates and confer resistance to nonnucleoside reverse transcriptase inhibitors (
Stereochemistry of halopyridyl and thiazolyl thiourea compounds is a major determinant of their potency as nonnucleoside inhibitors of HIV-1 reverse transcriptase.
Abstract: HI-511 R inhibited the HIV-strain A17 variant, containing RT mutations Y181C plus K103N, with an IC50 value of 2.7 microM, whereas the IC50 values of nevirapine, delavirdine, and trovirdine against this highly NNI-resistant HIV-1 strain were >100 microM.
Abstract: When tested against the NNI-resistant HIV-1 strain A17 with a Y181C mutation in RT, HI-511R was found to be 10,000-times more active than nevirapine, 5000-times more active than delavirdine, and 50-times more active than trovirdine.
Structure-based drug design of non-nucleoside inhibitors for wild-type and drug-resistant HIV reverse transcriptase.
Abstract: Modeling studies revealed that for an NNI of HIV RT to be active against RT mutants such as the especially problematic Y181C RT mutant, the following features are required: (a) the inhibitor should be highly potent against wild-type RT and therefore capable of tolerating a considerable activity loss against RT mutants.
Genetic diversity of protease and reverse transcriptase sequences in non-subtype-B human immunodeficiency virus type 1 strains: evidence of many minor drug resistance mutations in treatment-naive patients.
PMID: 11060045
2000
Journal of clinical microbiology
Abstract: Major mutations linked to resistance to non-NRTI agents were detected in all group O isolates (A98G and Y181C) and in one subtype J virus (V108I).
Piperidinylethyl, phenoxyethyl and fluoroethyl bromopyridyl thiourea compounds with potent anti-HIV activity.
Abstract: Notably, the lead fluorothiourea compounds 11 and 12 were both substantially more active against the NNRTI-resistant HIV strains RT-MDR (V106A) and A17 (Y181C) than nevirapine or delavirdine.
HIV mutation literature information.
PMID: 
2000
Antiviral chemistry & chemotherapy
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