Discovery of HIV-1 Integrase Inhibitors by Pharmacophore Searching
Journal of Medicinal Chemistry1997Vol. 40(6), pp. 930–936
Citations Over TimeTop 10% of 1997 papers
Huixiao Hong, Nouri Neamati, Shaomeng Wang, Marc C. Nicklaus, Abhijit Mazumder, He Zhao, Terrence R. Burke, Yves Pommier, G. W. A. Milne
Abstract
Based upon a class of known HIV-1 integrase inhibitors, several pharmacophore models were proposed from molecular modeling studies and validated using a 3D database of 152, compounds for which integrase assay data are known. Using the most probable pharmacophore model as the query, the NCI 3D database of 206,876 compounds was searched, and 340 compounds that contain the pharmacophore query were identified. Twenty-nine of these compounds were selected and tested in the HIV-1 integrase assay. This led to the discovery of 10 novel, structurally diverse HIV-1 integrase inhibitors, four of which have an IC50 value less than 30 microM and are promising lead compounds for further HIV-1 integrase inhibitor development.
Related Papers
- Characterization and structural analysis of HIV-1 integrase conservation.(2009)
- → Evolution of Integrase Resistance During Failure of Integrase Inhibitor-Based Antiretroviral Therapy(2010)73 cited
- → Rational design of 2-pyrrolinones as inhibitors of HIV-1 integrase(2011)68 cited
- → A refined pharmacophore model for HIV-1 integrase inhibitors: Optimization of potency in the 1H-benzylindole series(2008)33 cited
- A theoretical analysis of the relationships between electronic structure and HIV-1 integrase inhibition and antiviral activity of a series of naphthyridinone derivatives(2015)