Synthesis and evaluation of efavirenz (Sustiva) analogues as HIV-1 reverse transcriptase inhibitors: replacement of the cyclopropylacetylene side chain.
Abstract: Several members of both series show equivalent potency to efavirenz against both wild-type virus and the key K103N mutant.
Development of Novel Dihydrofuro[3,4-d]pyrimidine Derivatives as HIV-1 NNRTIs to Overcome the Highly Resistant Mutant Strains F227L/V106A and K103N/Y181C.
Abstract: Comparison of unliganded wild-type and Lys103Asn mutant HIV-1 RT structures reveals a network of hydrogen bonds in the Lys103Asn mutant that is not present in the wild-type enzyme.
Abstract: Design of NNRTIs that make favorable interactions with the Asn103 side-chain should be relatively effective against the Lys103Asn drug-resistant mutant.
Abstract: Hydrogen bonds in the unliganded Lys103Asn mutant but not in wild-type HIV-1 RT are observed between (1) the side-chains of Asn103 and Tyr188 and (2) well-ordered water molecules in the pocket and nearby pocket residues.
Abstract: Substitution of asparagine for lysine at position 103 of HIV-1 RT is a
An in vivo model for HIV resistance development.
PMID: 11375059
2001
AIDS research and human retroviruses
Abstract: This resulted in the selection of mutants with Y181C and K103N changes in RT, which correspond to the HIV-1 mutations in nevirapine-resistant HIV-1 patients.
4,1-Benzoxazepinone analogues of efavirenz (Sustiva) as HIV-1 reverse transcriptase inhibitors.
Abstract: The best compounds are potent orally bioavailable inhibitors of both wild-type HIV-1 and its clinically relevant K103N mutant virus, but are highly protein-bound in human plasma.
2-Amino-6-arylsulfonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1.
PMID: 11384233
2001
Journal of medicinal chemistry
Abstract: However, they showed a lack of activity against the K103N and Y181C mutant viruses.
High prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients receiving antiretroviral therapy in Abidjan, Cote d'Ivoire.
PMID: 11391173
2001
Journal of acquired immune deficiency syndromes (1999)
Abstract: The prevalence of mutations associated with resistance to ARV drugs was: 29 (42.6%) to zidovudine, 10 (14.7%) to lamivudine, one (1.5%) to didanosine, one K103N mutation (associated with resistance to delavirdine, nevirapine, and efavirenz), one Y181C mutation (associated with resistance to delavirdine and nevirapine), two to both indinavir (M46I/L and V82A) and saquinavir (G48V and L90M), and one each to ritonavir (V82A) and nelfinavir (D30N).
Development of Novel Dihydrofuro[3,4-d]pyrimidine Derivatives as HIV-1 NNRTIs to Overcome the Highly Resistant Mutant Strains F227L/V106A and K103N/Y181C.
PMID: 11418520
2001
The Journal of antimicrobial chemotherapy
Abstract: Group B patients had the highest prevalence of K103N+/Y181C.
Abstract: In conclusion, zidovudine seems not to determine the emergence of K103N; however, there appears to be an accumulation of NNRTI resistance mutations with sequential use of NNRTIs.
Abstract: No difference was found in the exposure to zidovudine or major zidovudine mutations between the resistance patterns K103N-/Y181C+, K103N+/Y181C- and K103N+/ Y181C+, either in group A (patients on nevirapine and previously NNRTI naive) or in group B (on any N
Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants.
Abstract: In contrast, three of five clones that did not have P236L (but had either K103N or Y181C) replicated significantly better than NL4-3 with P236L.
Abstract: Other NNRTI-resistance mutations, such as K103N and Y181C, do not reduce the replication capacity of NL4-3 as much as P236L and develop more frequently in HIV-1 isolates from patients failing delavirdine.
Synthesis and evaluation of novel quinolinones as HIV-1 reverse transcriptase inhibitors.
Abstract: The C-3 substituted compound 9h displayed improved antiviral activity against clinically significant single (K103N) and double (K103N/L100I) mutant viruses.
The stereoselective targeting of a specific enzyme-substrate complex is the molecular mechanism for the synergic inhibition of HIV-1 reverse transcriptase by (R)-(-)-PPO464: a novel generation of nonnucleoside inhibitors.
PMID: 11572864
2001
The Journal of biological chemistry
Abstract: Only one enantiomer, (R)-(-)-PPO464, displayed antiviral activity against both the wild type and the K103N mutant HIV-1 RT and was found to interact exclusively with the reaction intermediate formed by RT complexed with both the DNA and the nucleotide substrates.
HIV mutation literature information.
PMID: 
2001
Bioorganic & medicinal chemistry letters
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