Novel indole based NNRTIs with improved potency against wild type and resistant HIV
| Autor: | Ronel Müller, Stephen C. Pelly, Adriaan E. Basson, Nicole Pribut, Willem A. L. van Otterlo, Mohammad Hassam, Lynn Morris, Iqbal Mulani |
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| Rok vydání: | 2014 |
| Předmět: |
Indoles
Anti-HIV Agents Clinical Biochemistry Pharmaceutical Science Microbial Sensitivity Tests Disease Pharmacology Biology Biochemistry Virus Structure-Activity Relationship Acquired immunodeficiency syndrome (AIDS) Drug Discovery Pandemic medicine Potency Molecular Biology Indole test Dose-Response Relationship Drug Molecular Structure Organic Chemistry Wild type HIV medicine.disease Virology HIV Reverse Transcriptase Drug development Reverse Transcriptase Inhibitors Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 24:4376-4380 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2014.08.020 |
| Popis: | The human immunodeficiency virus (HIV) pandemic remains a significant problem, especially in developing nations where the social and economic impacts are severe. Until a cure or vaccine for the disease is found, a constant supply of new compounds to fill the drug development pipeline is a requirement, given the tendency for the virus to rapidly develop resistance to current therapies. Here we disclose our efforts to improve upon the efficacy of cyclopropyl-indole derivatives developed as NNRTIs in our laboratories. To this end, modifications to the functionality occupying the small Val179 pocket have resulted in nearly two orders of magnitude increase in potency. |
| Databáze: | OpenAIRE |
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