Rational Design of Potent, Bioavailable, Nonpeptide Cyclic Ureas as HIV Protease Inhibitors
| Autor: | Patrick Y. S. Lam, Prabhakar K. Jadhav, Charles J. Eyermann, C. Nicholas Hodge, Yu Ru, Lee T. Bacheler, James L. Meek, Michael J. Otto, Marlene M. Rayner, Y. Nancy Wong, Chong-Hwan Chang, Patricia C. Weber, David A. Jackson, Thomas R. Sharpe, Susan Erickson-Viitanen |
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| Rok vydání: | 1994 |
| Předmět: |
Models
Molecular Stereochemistry medicine.medical_treatment Drug Evaluation Preclinical Molecular Conformation Administration Oral Biological Availability Crystallography X-Ray Virus Replication Virus Cell Line Dogs HIV Protease medicine Animals Urea HIV Protease Inhibitor Binding site chemistry.chemical_classification Cyclic compound Binding Sites Multidisciplinary Protease biology Rational design Hydrogen Bonding Azepines HIV Protease Inhibitors Recombinant Proteins Rats Molecular Weight Enzyme chemistry Enzyme inhibitor Drug Design HIV-1 biology.protein |
| Zdroj: | Science. 263:380-384 |
| ISSN: | 1095-9203 0036-8075 |
| Popis: | Mechanistic information and structure-based design methods have been used to design a series of nonpeptide cyclic ureas that are potent inhibitors of human immunodeficiency virus (HIV) protease and HIV replication. A fundamental feature of these inhibitors is the cyclic urea carbonyl oxygen that mimics the hydrogen-bonding features of a key structural water molecule. The success of the design in both displacing and mimicking the structural water molecule was confirmed by x-ray crystallographic studies. Highly selective, preorganized inhibitors with relatively low molecular weight and high oral bioavailability were synthesized. |
| Databáze: | OpenAIRE |
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