title: Synthesis and SAR of thiophene containing kinesin spindle protein (KSP) inhibitors.
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.
authors.affiliation: Department of Medicinal Chemistry, Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, USA. apinkerton@kalypsys.com <apinkerton@kalypsys.com>
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Pinkerton
authors.forename: Tom T
authors.initials: TT
authors.lastname: Lee
authors.forename: Timothy Z
authors.initials: TZ
authors.lastname: Hoffman
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kahraman
authors.forename: Travis G
authors.initials: TG
authors.lastname: Cook
authors.forename: Daniel
authors.initials: D
authors.lastname: Severance
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Gahman
authors.forename: Stewart A
authors.initials: SA
authors.lastname: Noble
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Shiau
authors.forename: Robert L
authors.initials: RL
authors.lastname: Davis
mesh_terms: 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*
chemical_list: D000577:Amides; D050256:Antimitotic Agents; C470243:KIF11 protein, human; D013876:Thiophenes; D016547:Kinesins