Pyrimidine sulfonylacetanilides with improved potency against key mutant viruses of HIV-1 by specific targeting of a highly conserved residue
| Autor: | Tian-Qi Mao, Erik De Clercq, Zheng-Yong Wan, Jin Yao, Dirk Daelemans, Fen-Er Chen, Xinlong Wang, Christophe Pannecouque, Hong Yin, Wen-Xue Chen, Haifeng Wang |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Pyrimidine Anti-HIV Agents Allosteric regulation Mutant medicine.disease_cause Conserved sequence chemistry.chemical_compound Drug Discovery Tumor Cells Cultured medicine Humans Potency Conserved Sequence Pharmacology Mutation Molecular Structure Chemistry Organic Chemistry Biological activity General Medicine Molecular biology HIV Reverse Transcriptase Reverse transcriptase Pyrimidines Biochemistry HIV-1 Reverse Transcriptase Inhibitors Acetanilides |
| Zdroj: | European Journal of Medicinal Chemistry. 102:215-222 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2015.08.007 |
| Popis: | Based on molecular simulation, the etravirine-VRX-480773 hybrids previously disclosed by our group were optimized to yield novel pyrimidine sulfonylacetanilides 8 with improved activity against a panel of seven clinically relevant single and double mutant strains of HIV-1. The improvement in potency in this in vitro model of HIV RNA replication partly validates the mechanism by which this class of allosteric pyrimidine derivatives inhibits the reverse transcriptase (RT), and represents a remarkable step forward in the development of anti-HIV drugs. |
| Databáze: | OpenAIRE |
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