Article

Design and evaluation of a series of pyrazolopyrimidines as p70S6K inhibitors.

Exelixis, 210 E. Grand Avenue, South San Francisco, CA 94080, USA.
Bioorganic & medicinal chemistry letters (impact factor: 2.65). 03/2012; 22(6):2283-6. DOI:10.1016/j.bmcl.2012.01.105 pp.2283-6
Source: PubMed

ABSTRACT The 70-kDa ribosomal protein S6 kinase (p70S6K) is part of the PI3K/AKT/mTOR pathway and has been implicated in cancer. High throughput screening versus p70S6K led to the identification of aminopyrimidine 3a as active inhibitor. Lead optimization of 3a resulted in highly potent, selective, and orally bioavailable pyrazolopyrimidines. In this manuscript we report the structure-activity relationship of this series and pharmacokinetic, pharmacodynamic, and efficacy data of the lead compound 13c.

0 0
 · 
1 Bookmark
 · 
64 Views
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

70-kDa ribosomal protein S6 kinase
 
active inhibitor
 
aminopyrimidine 3a
 
efficacy data
 
lead compound 13c
 
orally bioavailable pyrazolopyrimidines
 
PI3K/AKT/mTOR pathway
 
selective
 
structure-activity relationship
 

Joerg Bussenius