Synthesis and SAR of thiophene containing kinesin spindle protein (KSP) inhibitors

Anthony B Pinkerton; Tom T Lee; Timothy Z Hoffman; Yan Wang; Mehmet Kahraman; Travis G Cook; Daniel Severance; Timothy C Gahman; Stewart A Noble; Andrew K Shiau; Robert L Davis

doi:10.1016/j.bmcl.2007.04.076

Synthesis and SAR of thiophene containing kinesin spindle protein (KSP) inhibitors

Bioorg Med Chem Lett. 2007 Jul 1;17(13):3562-9. doi: 10.1016/j.bmcl.2007.04.076. Epub 2007 Apr 29.

Authors

Anthony B Pinkerton¹, Tom T Lee, Timothy Z Hoffman, Yan Wang, Mehmet Kahraman, Travis G Cook, Daniel Severance, Timothy C Gahman, Stewart A Noble, Andrew K Shiau, Robert L Davis

Affiliation

¹ Department of Medicinal Chemistry, Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, USA. apinkerton@kalypsys.com <apinkerton@kalypsys.com>

PMID: 17498954
DOI: 10.1016/j.bmcl.2007.04.076

Abstract

We have identified and synthesized a series of thiophene containing inhibitors of kinesin spindle protein. SAR studies led to the synthesis of 33, which was co-crystallized with KSP and determined to bind to an allosteric pocket previously described for other known KSP inhibitors.

MeSH terms

Allosteric Site
Amides / chemistry
Antimitotic Agents / pharmacology
Cell Line, Tumor
Chemistry, Pharmaceutical / methods*
Crystallization
Crystallography, X-Ray
Drug Design
Humans
Inhibitory Concentration 50
Kinesins / antagonists & inhibitors*
Kinesins / chemistry
Models, Chemical
Models, Molecular
Molecular Conformation
Thiophenes / chemistry*

Substances

Amides
Antimitotic Agents
KIF11 protein, human
Thiophenes
Kinesins