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 ; 26(2): 454-459, 2016 Jan 15.
Article in English | MEDLINE | ID: mdl-26681511

ABSTRACT

A new series of pyrazolo[1,5-a]pyrimidines exemplified by compound 1, has been identified with moderate activity (IC50=165nM), following GSK256066 rescaffolding. Compound 1 optimization at positions 2, 3, 6 and 7 gave compound 10 with high in vitro activity (IC50=0.7nM). Modeling studies based on the PDB structure 3GWT with compound 5 showed the expected overlay with the carboxamide, the aryl moiety and the sulfone. Cyclisation of the primary amide to the 5 position of the pyrazolo[1,5-a]pyrimidines scaffold afforded compounds 15 and 16 with 200-fold enhancement in activity and cellular potency.


Subject(s)
Phosphodiesterase 4 Inhibitors/pharmacology , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Aminoquinolines/chemistry , Cell Line, Tumor , Cyclic AMP/biosynthesis , Humans , Models, Molecular , Phosphodiesterase 4 Inhibitors/chemical synthesis , Pyrazoles/chemical synthesis , Pyrimidines/chemical synthesis , Structure-Activity Relationship , Sulfones/chemical synthesis , Sulfones/chemistry , Sulfones/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL
...