dc.contributor.author |
Kendall, Jackie |
en |
dc.contributor.author |
Giddens, Anna |
en |
dc.contributor.author |
Tsang, KY |
en |
dc.contributor.author |
Frederick, R |
en |
dc.contributor.author |
Marshall, ES |
en |
dc.contributor.author |
Singh, R |
en |
dc.contributor.author |
Lill, CL |
en |
dc.contributor.author |
Lee, Woo Jeong |
en |
dc.contributor.author |
Kolekar, Sharada |
en |
dc.contributor.author |
Chao, M |
en |
dc.contributor.author |
Malik, Alisha |
en |
dc.contributor.author |
Yu, S |
en |
dc.contributor.author |
Chaussade, C |
en |
dc.contributor.author |
Buchanan, Christina |
en |
dc.contributor.author |
Rewcastle, Gordon |
en |
dc.contributor.author |
Baguley, Bruce |
en |
dc.contributor.author |
Flanagan, Jack |
en |
dc.contributor.author |
Jamieson, Stephen |
en |
dc.contributor.author |
Denny, William |
en |
dc.contributor.author |
Shepherd, Peter |
en |
dc.date.accessioned |
2012-06-12T22:01:16Z |
en |
dc.date.issued |
2012-01-01 |
en |
dc.identifier.citation |
Bioorganic and Medicinal Chemistry 20(1):58-68 Jan 2012 |
en |
dc.identifier.issn |
0968-0896 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/18960 |
en |
dc.description.abstract |
Structure–activity relationship studies of the pyrazolo[1,5-a]pyridine class of PI3 kinase inhibitors show that substitution off the hydrazone nitrogen and replacement of the sulfonyl both gave a loss of p110a selectivity, with the exception of an N-hydroxyethyl analogue. Limited substitutions were tolerated around the phenyl ring; in particular the 2,5-substitution pattern was important for PI3 kinase activity. The N-hydroxyethyl compound also showed good inhibition of cell proliferation and inhibition of phosphorylation of Akt/PKB, a downstream marker of PI3 kinase activity. It had suitable pharmacokinetics for evaluation in vivo, and showed tumour growth inhibition in two human tumour cell lines in xenograft studies. This work has provided suggestions for the design of more soluble analogues. |
en |
dc.publisher |
Elsevier Ltd. |
en |
dc.relation.ispartofseries |
Bioorganic & Medicinal Chemistry |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.title |
Novel pyrazolo[1,5-a]pyridines as p110α-selective PI3 kinase inhibitors: Exploring the benzenesulfonohydrazide SAR |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.bmc.2011.11.031 |
en |
pubs.issue |
1 |
en |
pubs.begin-page |
58 |
en |
pubs.volume |
20 |
en |
dc.rights.holder |
Copyright: Elsevier Ltd. |
en |
dc.identifier.pmid |
22177407 |
en |
pubs.author-url |
http://www.sciencedirect.com/science/article/pii/S0968089611009679 |
en |
pubs.end-page |
68 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
250380 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Auckland Cancer Research |
en |
pubs.org-id |
Molecular Medicine |
en |
pubs.org-id |
Pharmacology |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
dc.identifier.eissn |
1464-3391 |
en |
pubs.record-created-at-source-date |
2011-12-02 |
en |
pubs.dimensions-id |
22177407 |
en |