Cytotoxic and anti-mitotic compounds, and methods of using the same

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• R1 is selected from:
• amino-C1-C6 alkyl, amino-aryl, amino-C3-C7 cycloalkyl, amino-heterocyclyl, and heterocyclyl, each optionally substituted with one or more substituents selected from aryl, aryl-C1-C6 alkyl, C1-C6 alkyl, C1-C6 alkylthio, carboxyl, carboxamide, C3-C7 cycloalkyl, C3-C7 cycloalkyl-C1-C6 alkyl, guanidino, halo, C1-C6 haloalkyl, heterocyclyl, heterocyclyl-C1-C6 alkyl, hydroxyl, and thio;
• or
• R1 is RaRbNCH(Rc)—;
• Ra is selected from:
• H and C1-C6 alkyl;
• Rb is C1-C6 alkyl;
• and
• Rc is Rd—C(CH3)2—;
• and
• Rd is selected from:
• H, aryl, C3-C7 cycloalkyl, and heteroaryl, each of which is optionally substituted with one or more substituents selected from:
• C1-C4 acylthio, C2-C4 alkenyl, C1-C4 alkyl, C1-C4 alkylamino, C1-C4 alkyloxy, amino, amino-C1-C4 alkyl, halo, C1-C4 haloalkyl, hydroxyl, hydroxy-C1-C4 alkyl, and thio, wherein C2-C4 alkenyl, C1-C4 alkylamino and C1-C4 alkyloxy are further optionally substituted with one substituent selected from C1-C4 alkylaryl, hydroxyl, and thio;
• or
• Rb and Rc taken together with the atoms to which they are each bonded form a heterocyclyldiyl;
• R2 is selected from:
• C2-C6 alkyl, aryl, aryl-C1-C6 alkyl, C4-C7 cycloalkyl, C3-C7 cycloalkyl-C1-C6 alkyl, heteroaryl, heteroaryl-C1-C6 alkyl, and heterocyclyl, each optionally substituted with one or more substituents selected from:
• C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl, C1-C6 alkylamino, amino, amino-C1-C6 alkyl, amino-aryl, amino-C3-C7 cycloalkyl, aryl, carboxamide, carboxyl, cyano, C1-C6 haloacyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, halo, hydroxyl, nitro, thio, and thio-C1-C6 alkyl;
• and
• X is —C(O)NHCH(CH2R3)—;
• and
• R3 is selected from:
• aryl, heteroaryl, and C3-C7 cycloalkyl, each optionally substituted with one substituent selected from amino and hydroxyl;
• provided that when R1 is 2-methyl-1-(methylamino)propyl, and X is —C(O)NHCH(CH2Ph)-, R2 is other than ethyl, isopropyl, n-butyl, and phenyl.