Three-dimensional quantitative structure-activity relationships study on HIV-1 reverse transcriptase inhibitors in the class of dipyridodiazepinone derivatives, using comparative molecular field analysis.
PMID: 11155314
2000
Journal of molecular graphics & modelling
Abstract: A three-dimensional quantitative structure-activity relationships (3D QSAR) method, Comparative Molecular Field Analysis (CoMFA), was applied to a set of dipyridodiazepinone (nevirapine) derivatives active against wild-type (WT) and mutant-type (Y181C) HIV-1 reverse transcriptase.
Abstract: CoMFA contour maps reveal that steric and electrostatic interactions corresponding to the WT inhibition amount to 58.5% and 41.5%, respectively, while steric and electrostatic effects have approximately equal contributions for the explanation of inhibitory activities against Y181C.
Abstract: CoMFA was used to discriminate between structural requirements for WT and Y181C inhibitory activities.
Abstract: The resulting CoMFA models yield satisfactory predictive ability regarding WT and Y181C inhibitions, wit
Calanolides, the naturally occurring anti-HIV agents.
PMID: 19649847
2000
Current opinion in drug discovery & development
Abstract: Further enhancement of activity is observed with RTs that possess the Y181C change together with AZT-resistant mutations.
Abstract: Moreover, when challenged with viruses containing Y181C and K103N dual mutations, calanolide compounds remain active.
Abstract: Of particular interest is the use of calanolide in the treatment of patients who have failed other NNRTI therapy and developed the Y181C mutation or the Y181C/K103N dual mutations.
Abstract: These compounds also exhibit an enhanced antiviral activity against one of the most prevalent non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant vir
Argentine plant extracts active against polymerase and ribonuclease H activities of HIV-1 reverse transcriptase.
Abstract: 4) were examined in vitro for their ability to inhibit the polymerase and ribonuclease H (RNase H) activities of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) (wild and Y181C mutant types).
Abstract: These extracts were refractioned into four fractions; 2I4 and 4I4 were active as inhibitors of DNA-polymerase (wild and Y181C types) and RNase H activities.
Rational design of N-[2-(2,5-dimethoxyphenylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-236) as a potent non-nucleoside inhibitor of drug-resistant human immunodeficiency virus.
Abstract: RT assays revealed that HI-236 was not only more potent than trovirdine, MKC-442, and AZT against the drug-sensitive HIV-1 strain HTLV(IIIB), it was also 50-100 times more effective than delavirdine or nevirapine and twice as effective as our recently reported lead compound N-[2-(2-fluorophenethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-240) against the NNI-resistant Y181C mutant HIV-1 strain A17.
Unique anti-human immunodeficiency virus activities of the nonnucleoside reverse transcriptase inhibitors calanolide A, costatolide, and dihydrocostatolide.
PMID: 10428899
1999
Antimicrobial agents and chemotherapy
Abstract: Further enhancement of activity is observed with RTs that possess the Y181C change together with mutations that yield resistance to AZT.
Abstract: The calanolide analogs, however, exhibit 10-fold enhanced antiviral activity against drug-resistant viruses that bear the most prevalent NNRTI resistance that is engendered by amino acid change Y181C in the RT.
Rapid screening of phenotypic resistance to nevirapine by direct analysis of HIV type 1 reverse transcriptase activity in plasma.
PMID: 10480632
1999
AIDS research and human retroviruses
Abstract: Phenotypic resistance was seen in eight samples obtained after 1 week of treatment and was correlated with detection of the Y181C mutation.
Abstract: Preteatment samples and those obtained during the first 6 days of therapy (n = 21) were sensitive to nevirapine, and none had detectable Y181C mutation.
N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea and N'-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-chloropyridyl)]-thiourea as potent inhibitors of multidrug-resistant human immunodeficiency virus-1.
Abstract: HI-445 was also tested against the RT Y181C mutant A17 strain of HIV-1 and found to be >7-fold more effective than trovirdine and >1,400-fold more effective than nevirapine or delavirdine.
Abstract: Similarly, both HI-346 and HI-445 were more effective than trovirdine, nevirapine, and delavirdine against the problematic NNI-resistant HIV-1 strain A17-variant with both Y181C and K103N mutations in RT, although their activity was markedly reduced against this strain.
Synthesis and structure-activity relationships of the (alkylamino)piperidine-containing BHAP class of non-nucleoside reverse transcriptase inhibitors: effect of 3-alkylpyridine ring substitution.
PMID: 10514284
1999
Journal of medicinal chemistry
Abstract: The synthesis of analogues in which the usual 3-alkylamino substituent on the pyridine ring is replaced by a 3-alkyl substituent led to compounds which retained activity against recombinant P236L and wild-type (WT) reverse transcriptase (RT), while inhibition of the Y181C mutant RT was reduced relative to the activity of the 3-alkylamino-substituted congeners.
Structure-based design of non-nucleoside reverse transcriptase inhibitors of drug-resistant human immunodeficiency virus.
Abstract: HI-236 was more potent than trovirdine, MKC-442 and zidovudine against the drug-sensitive HIV-1 strain IIIB, 50-100 times more effective than delavirdine or nevirapine and twice as effective as our recently reported lead compound N-[2-(2-fluorophenethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-240) against the NNI-resistant Y181C mutant HIV-1 strain A17.
Design of MKC-442 (emivirine) analogues with improved activity against drug-resistant HIV mutants.
PMID: 10579814
1999
Journal of medicinal chemistry
Abstract: Both compounds showed approximately 30-fold greater inhibitory effect than MKC-442 to the Tyr181Cys mutant virus as well as to the clinically important Lys103Asn virus.
Abstract: Two analogues of the nonnucleoside inhibitor of HIV-1 RT, MKC-442 (emivirine), containing different C6 substituents have been designed to be less susceptible to the commonly found drug-resistance mutation of Tyr181Cys.
HIV mutation literature information.
PMID: 
2000
Journal of molecular graphics & modelling
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