Kinesin spindle protein (KSP) inhibitors. Part 2: The design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 7, 2006, Pages 1775-1779

  Fraley, Mark E ^a   Garbaccio, Robert M ^a   Arrington, Kenneth L ^a   Hoffman, William F ^a   Tasber, Edward S ^a   Coleman, Paul J ^a   Buser, Carolyn A ^a   Walsh, Eileen S ^a   Hamilton, Kelly ^a   Fernandes, Christine ^a   Schaber, Michael D ^a   Lobell, Robert B ^a   Tao, Weikang ^a   South, Victoria J ^a   Yan, Youwei ^a   Kuo, Lawrence C ^a   Prueksaritanont, Thomayant ^a   Shu, Cathy ^a   Torrent, Maricel ^a   Heimbrook, David C ^a   Kohl, Nancy E ^a   Huber, Hans E ^a   Hartman, George D ^a   more..

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Anticancer; Antimitotics; Antiproliferative; Dihydropyrroles; hERG; Kinesin spindle protein; KSP

Indexed keywords

ANTINEOPLASTIC AGENT; KINESIN SPINDLE PROTEIN INHIBITOR; PROTEIN INHIBITOR; PYRROLE DERIVATIVE; SB 715992; UNCLASSIFIED DRUG;

ACYLATION; AQUEOUS SOLUTION; ARTICLE; CANCER CELL; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG SYNTHESIS; HUMAN; HUMAN CELL; MITOSIS; MITOSIS INHIBITION; MOLECULAR EVOLUTION; OVARY CARCINOMA; OXIDATION; X RAY ANALYSIS;

CELL LINE, TUMOR; FEMALE; HUMANS; KINESIN; MITOTIC SPINDLE APPARATUS; MODELS, MOLECULAR; OVARIAN NEOPLASMS; PYRROLES;

EID: 33144468938     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.01.030     Document Type: Article

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13. 50 values
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17. Interestingly, use of LiHMDS under the same reaction conditions produced a 2:1 mixture of enol triflates, favoring 11.
18. As with the dihydropyrazoles, the 2,5-difluorophenyl ring was found to be optimal in the dihydropyrrole series (data not shown).
19. 50 values.
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23. Hydrophobic grids were calculated on an SGI and generated using a Morse potential and a Lennard-Jones repulsive VdW.