dc.contributor.author |
Miller, Christian |
en |
dc.contributor.author |
Huttunen, KM |
en |
dc.contributor.author |
Denny, William |
en |
dc.contributor.author |
Jaiswal, Jagdish |
en |
dc.contributor.author |
Ciccone, A |
en |
dc.contributor.author |
Browne, KA |
en |
dc.contributor.author |
Trapani, JA |
en |
dc.contributor.author |
Spicer, Julie |
en |
dc.coverage.spatial |
Vienna, Austria |
en |
dc.date.accessioned |
2016-01-28T20:16:13Z |
en |
dc.date.issued |
2016 |
en |
dc.identifier.citation |
Bioorganic and Medicinal Chemistry Letters, 2016, 26 (2), pp. 355 - 360 |
en |
dc.identifier.issn |
1464-3405 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/28137 |
en |
dc.description.abstract |
Evolution from a furan-containing high-throughput screen (HTS) hit (1) resulted in isobenzofuran-1(3H)-one (2) as a potent inhibitor of the function of both isolated perforin protein and perforin delivered in situ by intact KHYG-1 NK cells. In the current study, structure-activity relationship (SAR) development towards a novel series of diarylthiophene analogues has continued through the use of substituted-benzene and -pyridyl moieties as bioisosteres for 2-thioxoimidazolidin-4-one (A) on a thiophene (B) -isobenzofuranone (C) scaffold. The resulting compounds were tested for their ability to inhibit perforin lytic activity in vitro. Carboxamide (23) shows a 4-fold increase over (2) in lytic activity against isolated perforin and provides good rationale for continued development within this class. |
en |
dc.publisher |
Elsevier |
en |
dc.relation.ispartofseries |
Bioorganic and Medicinal Chemistry Letters |
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 |
Diarylthiophenes as inhibitors of the pore-forming protein perforin |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.bmcl.2015.12.003 |
en |
pubs.issue |
2 |
en |
pubs.begin-page |
355 |
en |
pubs.volume |
26 |
en |
dc.rights.holder |
Copyright:
Elsevier |
en |
dc.identifier.pmid |
26711151 |
en |
pubs.end-page |
360 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
440148 |
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 |
Science |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
dc.identifier.eissn |
1464-3405 |
en |
pubs.record-created-at-source-date |
2014-05-30 |
en |
pubs.dimensions-id |
26711151 |
en |