TY - JOUR
T1 - Discovery of pyrazolo[1,5-a]pyridines as p110α-selective PI3 kinase inhibitors
AU - Kendall, J.D.
AU - O'Connor, P.D.
AU - Marshall, A.J.
AU - Frédérick, R.
AU - Marshall, E.S.
AU - Rewcastle, G.W.
AU - Baguley, B.C.
AU - Flanagan, J.U.
AU - Jamieson, S.M.F.
AU - Denny, W.A.
AU - Chaussade, C.
AU - Buchanan, C.
AU - Shepherd, P.R.
AU - Lill, C.L.
AU - Lee, W.-J.
AU - Kolekar, S.
AU - Chao, M.
AU - Malik, A.
AU - Yu, S.
N1 - MEDLINE® is the source for the MeSH terms of this document.
PY - 2012/1/1
Y1 - 2012/1/1
N2 - We have made a novel series of pyrazolo[1,5-a]pyridines as PI3 kinase inhibitors, and demonstrated their selectivity for the p110α isoform over the other Class Ia PI3 kinases. We investigated the SAR around the pyrazolo[1,5-a]pyridine ring system, and found compound 5x to be a particularly potent example (p110α IC 0.9 nM). This compound inhibits cell proliferation and phosphorylation of Akt/PKB, a downstream marker of PI3 kinase activity, and showed in vivo activity in an HCT-116 human xenograft model.
AB - We have made a novel series of pyrazolo[1,5-a]pyridines as PI3 kinase inhibitors, and demonstrated their selectivity for the p110α isoform over the other Class Ia PI3 kinases. We investigated the SAR around the pyrazolo[1,5-a]pyridine ring system, and found compound 5x to be a particularly potent example (p110α IC 0.9 nM). This compound inhibits cell proliferation and phosphorylation of Akt/PKB, a downstream marker of PI3 kinase activity, and showed in vivo activity in an HCT-116 human xenograft model.
UR - http://www.scopus.com/inward/record.url?scp=84855202660&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2011.11.029
DO - 10.1016/j.bmc.2011.11.029
M3 - Article
AN - SCOPUS:84855202660
SN - 0968-0896
VL - 20
SP - 69
EP - 85
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 1
ER -