Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Bioorg Med Chem Lett ; 18(2): 721-5, 2008 Jan 15.
Article in English | MEDLINE | ID: mdl-18078751

ABSTRACT

A series of 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamides was synthesized and tested for their inhibition of HIV-1 integrase catalytic activity and HIV-1 replication in cells. Structure-activity studies around lead compound 5 indicated that a coplanar relationship of metal-binding heteroatoms provides optimal binding to the integrase active site. Identification of potency-enhancing substituents and adjustments in lipophilicity provided 17b which inhibits integrase-catalyzed strand transfer with an IC(50) value of 74 nM and inhibits HIV-1 replication in cell culture in the presence of 50% normal human serum with an IC(95) value of 63 nM.


Subject(s)
HIV Integrase Inhibitors/chemistry , HIV Integrase Inhibitors/pharmacology , HIV Integrase/drug effects , Pyrazines/chemistry , Pyrazines/pharmacology , Catalysis , Cell Line , HIV Integrase/metabolism , HIV Integrase Inhibitors/chemical synthesis , HIV-1/enzymology , HIV-1/physiology , Pyrazines/chemical synthesis , Structure-Activity Relationship , Virus Replication/drug effects
SELECTION OF CITATIONS
SEARCH DETAIL
...