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.
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.
Roecker
Anthony J
AJ
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, Sumneytown Pike, West Point, PA 19486, USA. anthony_roecker@merck.com
Coleman
Paul J
PJ
Mercer
Swati P
SP
Schreier
John D
JD
Buser
Carolyn A
CA
Walsh
Eileen S
ES
Hamilton
Kelly
K
Lobell
Robert B
RB
Tao
Weikang
W
Diehl
Ronald E
RE
South
Vicki J
VJ
Davide
Joseph P
JP
Kohl
Nancy E
NE
Yan
Youwei
Y
Kuo
Lawrence C
LC
Li
Chunze
C
Fernandez-Metzler
Carmen
C
Mahan
Elizabeth A
EA
Prueksaritanont
Thomayant
T
Hartman
George D
GD
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
D011720:Pyrazoles; D006859:Hydrogen; D016547:Kinesins