Kinesin spindle protein (KSP) inhibitors. Part 7: Design and synthesis of 3,3-disubstituted dihydropyrazolobenzoxazines as potent inhibitors of the mitotic kinesin KSP.

Kinesin spindle protein (KSP) inhibitors. Part 7: Design and synthesis of 3,3-disubstituted dihydropyrazolobenzoxazines as potent inhibitors of the mitotic kinesin KSP. Research Abstract Details 

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Kinesin spindle protein (KSP) inhibitors. Part 7: Design and synthesis of 3,3-disubstituted dihydropyrazolobenzoxazines as potent inhibitors of the mitotic kinesin KSP. Abstract Text:

Robert M Garbaccio,Edward S Tasber,Lou Anne Neilson,Paul J Coleman,Mark E Fraley,Christy Olson,Jeff Bergman,Maricel Torrent,Carolyn A Buser,Keith Rickert,Eileen S Walsh,Kelly Hamilton,Robert B Lobell,Weikang Tao,Vicki J South,Ronald E Diehl,Joseph P Davide,Youwei Yan,Lawrence C Kuo,Chunze Li,Thomayant Prueksaritanont,Carmen Fernandez-Metzler,Elizabeth A Mahan,Donald E Slaughter,Joseph J Salata,Nancy E Kohl,Hans E Huber,George D Hartman,Robert M Garbaccio,Edward S Tasber,Lou Anne Neilson,Paul J Coleman,Mark E Fraley,Christy Olson,Jeff Bergman,Maricel Torrent,Carolyn A Buser,Keith Rickert,Eileen S Walsh,Kelly Hamilton,Robert B Lobell,Weikang Tao,Vicki J South,Ronald E Diehl,Joseph P Davide,Youwei Yan,Lawrence C Kuo,Chunze Li,Thomayant Prueksaritanont,Carmen Fernandez-Metzler,Elizabeth A Mahan,Donald E Slaughter,Joseph J Salata,Nancy E Kohl,Hans E Huber,George D Hartman,

Observations from two structurally related series of KSP inhibitors led to the proposal and discovery of dihydropyrazolobenzoxazines that possess ideal properties for cancer drug development. The synthesis and characterization of this class of inhibitors along with relevant pharmacokinetic and in vivo data are presented. The synthesis is highlighted by a key [3+2] cycloaddition to form the pyrazolobenzoxazine core followed by diastereospecific installation of a quaternary center.

Kinesin spindle protein (KSP) inhibitors. Part 7: Design and synthesis of 3,3-disubstituted dihydropyrazolobenzoxazines as potent inhibitors of the mitotic kinesin KSP. Publishing Authors By Initials

RM Garbaccio,ES Tasber,LA Neilson,PJ Coleman,ME Fraley,C Olson,J Bergman,M Torrent,CA Buser,K Rickert,ES Walsh,K Hamilton,RB Lobell,W Tao,VJ South,RE Diehl,JP Davide,Y Yan,LC Kuo,C Li,T Prueksaritanont,C Fernandez-Metzler,EA Mahan,DE Slaughter,JJ Salata,NE Kohl,HE Huber,GD Hartman,RM Garbaccio,ES Tasber,LA Neilson,PJ Coleman,ME Fraley,C Olson,J Bergman,M Torrent,CA Buser,K Rickert,ES Walsh,K Hamilton,RB Lobell,W Tao,VJ South,RE Diehl,JP Davide,Y Yan,LC Kuo,C Li,T Prueksaritanont,C Fernandez-Metzler,EA Mahan,DE Slaughter,JJ Salata,NE Kohl,HE Huber,GD Hartman,

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Kinesin spindle protein (KSP) inhibitors. Part 7: Design and synthesis of 3,3-disubstituted dihydropyrazolobenzoxazines as potent inhibitors of the mitotic kinesin KSP. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Bioorganic & medicinal chemistry letters

VOLUME: 17

Page Numbers: 5671-6

Journal Abbreviation: Bioorg. Med. Chem. Lett.

ISSN: 0960-894X

DAY: 21

MONTH: 08

YEAR: 2007

Kinesin spindle protein (KSP) inhibitors. Part 7: Design and synthesis of 3,3-disubstituted dihydropyrazolobenzoxazines as potent inhibitors of the mitotic kinesin KSP. Information

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LANGUAGE: eng

NlmUniqueID: 9107377

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Grant and Affiliation Information for Kinesin spindle protein (KSP) inhibitors. Part 7: Design and synthesis of 3,3-disubstituted dihydropyrazolobenzoxazines as potent inhibitors of the mitotic kinesin KSP.

AFFILIATION: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. robert_garbaccio@merck.com

Country: England

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MEDLINETA: Bioorg Med Chem Lett

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