Structure-Based Design of Novel Dihydroalkoxybenzyloxopyrimidine Derivatives as Potent Nonnucleoside Inhibitors of the Human Immunodeficiency Virus Reverse Transcriptase
| Autor: | Lisa Tuel-Ahlgren, Chen Mao, Fatih M. Uckun, Elise Sudbeck, Taracad K. Venkatachalam, Rakesh Vig |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Models
Molecular Pyrimidinones Sulfides Crystallography X-Ray Antiviral Agents Peripheral blood mononuclear cell Virus Structure-Activity Relationship Humans Pharmacology (medical) Binding site Cytotoxicity Pharmacology chemistry.chemical_classification Binding Sites biology Hydrogen Bonding Biological activity Virology HIV Reverse Transcriptase Recombinant Proteins Reverse transcriptase Infectious Diseases Enzyme chemistry Enzyme inhibitor Drug Design biology.protein Reverse Transcriptase Inhibitors |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 42:3225-3233 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.42.12.3225 |
| Popis: | Two highly potent dihydroalkoxybenzyloxopyrimidine (DABO) derivatives targeting the nonnucleoside inhibitor (NNI) binding site of human immunodeficiency virus (HIV) reverse transcriptase (RT) have been designed based on the structure of the NNI binding pocket and tested for anti-HIV activity. Our lead DABO derivative, 5-isopropyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1 H )-one, elicited potent inhibitory activity against purified recombinant HIV RT and abrogated HIV replication in peripheral blood mononuclear cells at nanomolar concentrations (50% inhibitory concentration |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|