Structural modifications of CH(OH)-DAPYs as new HIV-1 non-nucleoside reverse transcriptase inhibitors
| Autor: | Xiayun Huang, Wen-Xue Chen, Zi-Hong Yan, Christophe Pannecouque, Fen-Er Chen, Hai-Qiu Wu, Erik De Clercq, Qiu-Qin He |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Nevirapine
Pyrimidine Stereochemistry Clinical Biochemistry Human immunodeficiency virus (HIV) Pharmaceutical Science medicine.disease_cause Biochemistry Nucleoside Reverse Transcriptase Inhibitor Cell Line chemistry.chemical_compound Structure-Activity Relationship Drug Discovery medicine Humans Molecular Biology Binding Sites Chemistry Organic Chemistry HIV Reverse Transcriptase Protein Structure Tertiary Molecular Docking Simulation Pyrimidines Cell culture HIV-1 Molecular Medicine Reverse Transcriptase Inhibitors Linker medicine.drug |
| Zdroj: | Bioorganicmedicinal chemistry. 22(8) |
| ISSN: | 1464-3391 |
| Popis: | A series of CR 2 (OH)-diarylpyrimidine derivatives (CR 2 (OH)-DAPYs) featuring a hydrophobic group at CH(OH) linker between wing I and the central pyrimidine were synthesized and evaluated for their anti-HIV activity in MT-4 cell cultures. All the target compounds except for compound 3k displayed inhibitory activity against HIV-1 wild-type with EC 50 values ranging from 7.21 ± 1.99 to 0.067 ± 0.006 μM. Among them, compound 3d showed the most potent anti-HIV-1 activity (EC 50 = 0.067 ± 0.006 μM, SI > 592), which was approximately 2-fold more potent than the reference drugs nevirapine (NVP) and delaviridine (DLV) in the same assay. In addition, the binding modes with HIV-1 RT and the preliminary SAR studies of these new derivatives were also investigated. |
| Databáze: | OpenAIRE |
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