Inhibitors to tubulin polymerization

A compound of the formula (1)

• or a pharmaceutically acceptable salt thereof, wherein
• R1 and R2 are independently selected from the group consisting of —H, halo, C1–C6 alkyl, halogenated-C1–C6-alkyl, and —OR4, or
• R1 and R2 together with the carbon to which they are attached form a heterocyclyl;
• R4 is selected from the group consisting of C1–C6 alkyl, or
• R4 is aryl or aryl-C1–C6-alkyl, wherein the aryl portion is optionally substituted with one to four groups independently selected from halo, cyano, oxo, carboxy, formyl, nitro, amino, amidino, guanidino, —(CH2)5—NR30R31, or
• C1–C5 alkyl or alkenyl or arylalkyl imino, carbamoyl, azido, carboxamido, mercapto, hydroxy, hydroxyalkyl, alkylaryl, arylalkyl, C1–C8 alkyl, C1–C8 alkenyl, C1–C8 alkoxy, C1–C8 alkoxycarbonyl, aryloxycarbonyl, C2–C8 acyl, C2–C8 acylamino, C1–C8 alkylthio, arylalkylthio, arylthio, C1–C8 alkylsulfinyl, arylalkylsulfinyl, arylsulfinyl, C1–C8 alkylsulfonyl, arylalkylsulfonyl, arylsulfonyl, C0–C6 N-alkyl carbamoyl, C2–C15 N,N-dialkylcarbamoyl, C3–C7 cycloalkyl, aroyl, aryloxy, arylalkyl ether, aryl, aryl fused to a cycloalkyl or heterocycle or another aryl ring, C3–C7 heterocycle, or any of these rings fused or spiro-fused to a cycloalkyl, heterocyclyl, or aryl, each of which is optionally substituted with one or more groups independently selected from halo, cyano, oxo, carboxy, formyl, nitro, amino, amidino or guanidine;
• R30 and R31 are each independently hydrogen, cyano, oxo, carboxamido, amidino, C1–C8 hydroxyalkyl, C1–C3 alkylaryl, aryl-C1–C3 alkyl, C1–C8 alkyl, C1–C8 alkenyl, C1–C8 alkoxycarbonyl, aryloxycarbonyl, aryl-C1–C3 alkoxycarbonyl, C2–C8 acyl, C1–C8 alkylsulfonyl, arylalkylsulfonyl, arylsulfonyl, aroyl, aryl, cycloalkyl, heterocyclyl, or heteroaryl, wherein each optionally substituted with one more groups selected from halo, cyano, oxo, carboxy, formyl, nitro, amino, amidino, guanidine, or
• R30 and R31 taken together with the N to which they are attached form a heterocyclyl or heteroaryl, each of which is optionally substituted with from 1 to 3 substituents selected from halo, cyano, oxo, carboxy, formyl, nitro, amino, amidino, guanidine;
• L is selected from the group consisting of a covalent bond, C1–C6 alkyl, —C(O)—, and —(CH2)0-3C(H)(R5)—;
• R5 is selected from the group consisting of C1–C6 alkyl, aryl, aryl-C1–C6-alkyl, —R6—S—R7, —R6—C(O)OR7, and —R6—O—R7, wherein R6 and R7 are C1–C6 alkyl;
• R3 is selected from the group consisting of H, C1–C6 alkyl, hydroxy C1–C6 alkyl, —OR8, —C(O)OR9, —N(R10)R11, or
• R3 is C3–C8-cycloalkyl, heterocyclyl, aryl, heteroaryl, arylalkyl, each of which is optionally substituted with one to four groups selected from halo, cyano, oxo, carboxy, formyl, nitro, amino, amidino, guanidino, —(CH2)s—NR30R31, or
• C1–C5 alkyl or alkenyl or arylalkyl imino, carbamoyl, azido, carboxamido, mercapto, hydroxy, hydroxyalkyl, alkylaryl, arylalkyl, C1–C8 alkyl, C1–C8 alkenyl, C1–C8 alkoxy, C1–C8 alkoxycarbonyl, aryloxycarbonyl, C2–C8 acyl, C2–C8 acylamino, C1–C8 alkylthio, arylalkylthio, arylthio, C1–C8 alkylsulfinyl, arylalkylsulfinyl, arylsulfinyl, C1–C8 alkylsulfonyl, arylalkylsulfonyl, arylsulfonyl, C0–C6 N-alkyl carbamoyl, C2–C15 N,N-dialkylcarbamoyl, C3–C7 cycloalkyl, aroyl, aryloxy, arylalkyl ether, aryl, aryl fused to a cycloalkyl or heterocycle or another aryl ring, C3–C7 heterocycle, or any of these rings fused or spiro-fused to a cycloalkyl, heterocyclyl, or aryl, each of which is optionally substituted with one or more groups independently selected from halo, cyano, oxo, carboxy, formyl, nitro, amino, amidino or guanidine;
• R8 is C1–C6 alkyl or hydroxy C1–C6 alkyl;
• and
• R9, R10, and R11 are C1–C6 alkyl.