title: Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.
abstract: Inspired by previous efforts in the pyrazolobenzoxazine class of KSP inhibitors, the design and synthesis of 1,4-diaryl-4,5-dihydropyrazole inhibitors of KSP are described. Crystallographic evidence of binding mode and in vivo potency data is also highlighted.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, Sumneytown Pike, West Point, PA 19486, USA. anthony_roecker@merck.com
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Roecker
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Coleman
authors.forename: Swati P
authors.initials: SP
authors.lastname: Mercer
authors.forename: John D
authors.initials: JD
authors.lastname: Schreier
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Buser
authors.forename: Eileen S
authors.initials: ES
authors.lastname: Walsh
authors.forename: Kelly
authors.initials: K
authors.lastname: Hamilton
authors.forename: Robert B
authors.initials: RB
authors.lastname: Lobell
authors.forename: Weikang
authors.initials: W
authors.lastname: Tao
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Diehl
authors.forename: Vicki J
authors.initials: VJ
authors.lastname: South
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Davide
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Kohl
authors.forename: Youwei
authors.initials: Y
authors.lastname: Yan
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Kuo
authors.forename: Chunze
authors.initials: C
authors.lastname: Li
authors.forename: Carmen
authors.initials: C
authors.lastname: Fernandez-Metzler
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mahan
authors.forename: Thomayant
authors.initials: T
authors.lastname: Prueksaritanont
authors.forename: George D
authors.initials: GD
authors.lastname: Hartman
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D006859:Hydrogen / Q000737:chemistry*; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects*; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D011720:Pyrazoles; D006859:Hydrogen; D016547:Kinesins