Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Synthesis and structure-activity relationships of benzothienothiazepinone inhibitors of protein kinase D

Bravo-Altamirano, K and George, KM and Frantz, MC and Lavalle, CR and Tandon, M and Leimgruber, S and Sharlow, ER and Lazo, JS and Wang, QJ and Wipf, P (2011) Synthesis and structure-activity relationships of benzothienothiazepinone inhibitors of protein kinase D. ACS Medicinal Chemistry Letters, 2 (2). 154 - 159.

[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)


Protein kinase D (PKD) is a member of a novel family of serine/threonine kinases that regulate fundamental cellular processes. PKD is implicated in the pathogenesis of several diseases, including cancer. Progress in understanding the biological functions and therapeutic potential of PKD has been hampered by the lack of specific inhibitors. The benzoxoloazepinolone CID755673 was recently identified as the first potent and selective PKD inhibitor. The study of structure-activity relationships (SAR) of this lead compound led to further improvements in PKD1 potency. We describe herein the synthesis and biological evaluation of novel benzothienothiazepinone analogues. We achieved a 10-fold increase in the in vitro PKD1 inhibitory potency for the second generation lead kb-NB142-70 and accomplished a transition to an almost equally potent novel pyrimidine scaffold, while maintaining excellent target selectivity. These promising results will guide the design of pharmacological tools to dissect PKD function and pave the way for the development of potential anticancer agents. © 2010 American Chemical Society.


Social Networking:
Share |


Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Bravo-Altamirano, K
George, KM
Frantz, MC
Lavalle, CR
Tandon, M
Leimgruber, S
Sharlow, ER
Lazo, JS
Wang, QJ
Wipf, Ppwipf@pitt.eduPWIPF
Date: 10 February 2011
Date Type: Publication
Journal or Publication Title: ACS Medicinal Chemistry Letters
Volume: 2
Number: 2
Page Range: 154 - 159
DOI or Unique Handle: 10.1021/ml100230n
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
PubMed Central ID: PMC3100199
PubMed ID: 21617763
Date Deposited: 28 May 2013 15:35
Last Modified: 04 Feb 2019 15:57


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item