Triazole compounds as ksp inhibitors
AssigneeNovartis AG
InventorsTinya ABRAMS, Paul A. BARSANTI, Yu DING, David DUHL, Wooseok HAN, Cheng HU, Yue PAN
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Abstract
The present invention provides triazole compounds of Formula I: as further described herein. The invention also provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, and a method of treating a disorder mediated, at least in part, by KSP in a mammalian patient comprising administering to a mammalian patient in need of such treatment a therapeutically effective amount of a compound of Formula I.
Claims34
A compound of Formula I
- wherein:
- R1 is selected from C1-6 alkoxy-C1-4-alkyl, C1-6 straight chain alkyl, C3-6 branched alkyl, and —C3-6 cyclo alkyl;
- R2 is selected from H, and C1-6 straight chain alkyl;
- R3 represents —(CH2)0-3 substituted or unsubstituted pyrrolidinyl;
- R4 is selected from —C(O)—CH2OH, —C(O)-tetrahydrofuranyl, —C(O)—CH(CH3)—OH, —C(O)-unsubstituted morpholinyl, and —C(O)-morpholinyl substituted with up to three alkyl groups;
- R5 is selected from substituted or unsubstituted benzyl, wherein the substituents are selected from Cl, F, Br, and I;
- and
- R6 is selected from phenyl substituted with up to three halogen atoms.
A compound of Formula I selected from
- and the pharmaceutically acceptable salts of these compounds.
A compound of Formula (II):
- wherein,
- R1 is selected from C1-6 alkoxy-C1-4-alkyl, C1-6 straight chain alkyl, C3-6 branched alkyl, and —C3-6 cyclo alkyl;
- R3 represents —(CH2)0-3-substituted or unsubstituted pyrrolidinyl or C3-5 alkyl substituted with up to three groups selected from amino and halo;
- R4 is selected from —C(O)—CH2OH, —C(O)-tetrahydrofuranyl, —C(O)—CH(CH3)—OH, —C(O)-unsubstituted morpholinyl, and —C(O)-morpholinyl substituted with up to three alkyl groups;
- R5 is selected from substituted or unsubstituted benzyl, wherein the substituents are selected from Cl, F, Br, and I;
- and
- R6 is selected from phenyl substituted with up to three halogen atoms.
A method to make a fluorinated pyrrolidine, which comprises reacting a trans-3,4-disubstituted protected pyrrolidine of Formula V
- with a fluorination reagent to provide a compound of Formula VI:
- and oxidizing the compound of Formula VI to an aldehyde of Formula VII:
- wherein PG represents a protecting group, and R is selected from H and an optionally substituted alkyl or aryl group.
Dependencies are inferred from the claim text.