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.
Pinkerton
Anthony B
AB
Department of Medicinal Chemistry, Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, USA. apinkerton@kalypsys.com <apinkerton@kalypsys.com>
Lee
Tom T
TT
Hoffman
Timothy Z
TZ
Wang
Yan
Y
Kahraman
Mehmet
M
Cook
Travis G
TG
Severance
Daniel
D
Gahman
Timothy C
TC
Noble
Stewart A
SA
Shiau
Andrew K
AK
Davis
Robert L
RL
D000495:Allosteric Site; D000577:Amides / Q000737:chemistry; D050256:Antimitotic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D013876:Thiophenes / Q000737:chemistry*
D000577:Amides; D050256:Antimitotic Agents; C470243:KIF11 protein, human; D013876:Thiophenes; D016547:Kinesins