Receptor-type kinase modulators and methods of use

A compound for modulating tyrosine kinase activity of Formula I,

• or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein,
• R1 is C1-C3 alkyl optionally substituted with between one and three R50 substituents;
• R2 is selected from —H, halogen, trihalomethyl, —CN, —NH2, —NO2, —OR3, —N(R3)R4, —S(O)0-2R4, —SO2N(R3)R4, —CO2R3, —C(═O)N(R3)R4, —N(3)SO2R4, —N(R3)C(═O)R3, —N(R3)CO2R4, —C(═O)R3, optionally substituted lower alkyl, optionally substituted lower alkenyl, and optionally substituted lower alkynyl;
• R3 is —H or R4;
• R4 is selected from optionally substituted lower alkyl, optionally substituted aryl, optionally substituted lower arylalkyl, optionally substituted heterocyclyl, and optionally substituted lower heterocyclylalkyl;
• or
• R3 and R4, when taken together with a common nitrogen to which they are attached, form an optionally substituted five- to seven-membered heterocyclyl, said optionally substituted five- to seven-membered heterocyclyl optionally containing at least one additional heteroatom selected from N, O, S, and P;
• q is zero to five;
• Z is selected from —OCH2—, —O—, —S(O)0-2—, —N(R5)CH2—, and —NR5—;
• R3 is —H or optionally substituted lower alkyl;
• M1 is —H, C1-C8 alkyl-L2-L1- optionally substituted by R50, G(CH2)0-3—, or R53(R54)N(CH2)0-3—;
• wherein G is a saturated five- to seven-membered heterocyclyl containing one or two annular heteroatoms and optionally substituted with between one and three R50 substituents;
• L1 is —C═O— or —SO2—;
• L2 is a direct bond, —O—, or —NH—;
• and R53 and R54 are independently C1-C3 alkyl optionally substituted with between one and three R50 substituents;
• M2 is a saturated or mono- or poly-unsaturated C3-C14 mono- or fused-polycyclic hydrocarbyl optionally containing one, two, or three annular heteroatoms per ring and optionally substituted with between zero and four R50 substituents;
• and
• M3 is —NR9—, —O—, or absent;
• M4 is —CH2—, —CH2CH2—, —CH2CH2CH2—, or absent;
• R9 is —H or optionally substituted lower alkyl;
• R50 is —H, halo, trihalomethyl, —OR3, —N(R3)R4, —S(O)0-2R4, —SO2N(R2)R4, —CO2R3, —C(═O)N(R3)Re, —C(═NR21)N(R3)R4, —C(═NR25)R4, —N(R3)SO2R4, —N(R3)C(O)R3, —NCO2R3, —C(═O)R3, optionally substituted alkoxy, optionally substituted lower alkyl, optionally substituted aryl, optionally substituted lower arylalkyl, optionally substituted heterocyclyl, and optionally substituted lower heterocyclylalkyl;
• or
• two of R50, when taken together on the same carbon are oxo;
• or
• two of R50, when taken together with a common carbon to which they are attached, form a optionally substituted three- to seven-membered spirocyclyl, said optionally substituted three- to seven-membered spirocyclyl optionally containing at least one additional heteroatom selected from N, O, S, and P;
• and
• R25 is selected from —H, —CN, —NO2, —OR3, —S(O)0-2R4, —CO2R3, optionally substituted lower alkyl, optionally substituted lower alkenyl, and optionally substituted lower alkynyl.