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

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. We have identified...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2007-07, Vol.17 (13), p.3562-3569
Hauptverfasser:	Pinkerton, Anthony B., Lee, Tom T., Hoffman, Timothy Z., Wang, Yan, Kahraman, Mehmet, Cook, Travis G., Severance, Daniel, Gahman, Timothy C., Noble, Stewart A., Shiau, Andrew K., Davis, Robert L.
Format:	Artikel
Sprache:	eng
Schlagworte:	Allosteric Site Amides - chemistry Anti-mitotics Antimitotic Agents - pharmacology Antineoplastic agents Biological and medical sciences Cell Line, Tumor Chemistry, Pharmaceutical - methods Crystallization Crystallography, X-Ray Drug Design Eg5 General aspects Humans Inhibitory Concentration 50 Kinesin - antagonists & inhibitors Kinesin - chemistry Kinesin spindle protein KSP Medical sciences Models, Chemical Models, Molecular Molecular Conformation Pharmacology. Drug treatments Thiophenes Thiophenes - chemistry
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	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. 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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2007.04.076