Discovery of novel benzothiazolesulfonamides as potent inhibitors of HIV-1 protease
| Autor: | Srinivasan Nagarajan, Gary Anthony De Crescenzo, James A. Sikorski, Getman Daniel P, Jeffrey L Walker, Lisa Blystone, Christie L Funkes-Shippy, Nandini Kishore, Pramod P. Mehta, Kathryn A Houseman, Geralyn P. Kocan, Hwang Fun Lu, Joseph J. McDonald |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_treatment
Clinical Biochemistry Administration Oral Biological Availability Pharmaceutical Science Biochemistry Virus Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound HIV Protease HIV-1 protease Drug Discovery medicine Animals Humans Urea Structure–activity relationship Molecular Biology chemistry.chemical_classification Sulfonamides Protease biology Organic Chemistry HIV Protease Inhibitors Sulfanilamide Rats Thiazoles Enzyme chemistry Benzothiazole Enzyme inhibitor biology.protein Molecular Medicine medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry. 11:4769-4777 |
| ISSN: | 0968-0896 |
| Popis: | The human immunodeficiency virus (HIV) has been shown to be the causative agent for AIDS. The HIV virus encodes for a unique aspartyl protease that is essential for the production of enzymes and proteins in the final stages of maturation. Protease inhibitors have been useful in combating the disease. The inhibitors incorporate a variety of isosteres including the hydroxyethylurea at the protease cleavage site. We have shown that the replacement of t-butylurea moiety by benzothiazolesulfonamide provided inhibitors with improved potency and antiviral activities. Some of the compounds have shown good oral bioavailability and half-life in rats. The synthesis of benzothiazole derivatives led us to explore other heterocycles. During the course of our studies, we also developed an efficient synthesis of benzothiazole-6-sulfonic acid via a two-step procedure starting from sulfanilamide. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect