2. Academic Validation
  3. 5,6,7,8-Tetrahydro-1,6-naphthyridine Derivatives as Potent HIV-1-Integrase-Allosteric-Site Inhibitors

5,6,7,8-Tetrahydro-1,6-naphthyridine Derivatives as Potent HIV-1-Integrase-Allosteric-Site Inhibitors

  • J Med Chem. 2019 Feb 14;62(3):1348-1361. doi: 10.1021/acs.jmedchem.8b01473.
Kevin M Peese,  Christopher W Allard,  Timothy Connolly,  Barry L Johnson,  Chen Li,  Manoj Patel,  Margaret E Sorensen,  Michael A Walker,  Nicholas A Meanwell,  Brian McAuliffe,  Beatrice Minassian,  Mark Krystal,  Dawn D Parker,  Hal A Lewis,  Kevin Kish,  Ping Zhang,  Robert T Nolte 1,  Jean Simmermacher,  Susan Jenkins,  Christopher Cianci,  B Narasimhulu Naidu
Affiliations

Affiliation

  • 1 Protein Cellular and Structural Sciences , GlaxoSmithKline , 1250 South Collegeville Rd. , Collegeville , Pennsylvania 19426 , United States.
PMID: 30609350 DOI: 10.1021/acs.jmedchem.8b01473
Abstract

A series of 5,6,7,8-tetrahydro-1,6-naphthyridine derivatives targeting the allosteric lens-epithelium-derived-growth-factor-p75 (LEDGF/p75)-binding site on HIV-1 integrase, an attractive target for Antiviral chemotherapy, was prepared and screened for activity against HIV-1 Infection in Cell Culture. Small molecules that bind within the LEDGF/p75-binding site promote aberrant multimerization of the integrase Enzyme and are of significant interest as HIV-1-replication inhibitors. Structure-activity-relationship studies and rat pharmacokinetic studies of lead compounds are presented.

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