Tyrosine kinase inhibitors

A method of modulating the catalytic activity of Insulin-Like Growth Factor I receptor (IGF-1R or Insulin receptor (IR) comprising contacting the (IGF-1R or IR with a compound of Formula I:

• wherein:
• R1a and R1b are independently selected from:
• 1) hydrogen,
• 2) unsubstituted or substituted C1-C10 alkyl,
• 3) OR3,
• 4) N(R3)2,
• 5) unsubstituted or substituted aryl,
• 6) unsubstituted or substituted heterocycle, and
• 7) unsubstituted or substituted C3-C10 cycloalkyl;
• R1c is independently selected from:
• 1) hydrogen,
• 2) C1-C10 alkyl,
• 3) OR3,
• 4) N(R3)2,
• 5) C3-C10 cycloalkyl,
• 6) aryl, and
• 7) heterocycle;
• said alkyl, cycloalkyl, aryl and heterocycle is optionally substituted with at least one substituent selected from R7;
• R2 is independently selected from:
• 1) hydrogen,
• 2) unsubstituted or substituted C1-C10 alkyl,
• 3) N(R3)2,
• 4) OR3,
• 5) unsubstituted or substituted aryl, and
• 6) unsubstituted or substituted C3-C10 cycloalkyl;
• R3 is independently selected from:
• 1) hydrogen,
• 2) C1-C10 alkyl,
• 3) aryl,
• 4) heterocycle,
• 5) C3-C10 cycloalkyl,
• 6) CF3,
• 7) C2-C6 alkenyl,
• 8) C2-C6 alkynyl,
• 9) S(O)mR6, and
• 10) C(O)R6;
• said alkyl, cycloalkyl, aryl, heterocycle, alkynyl, and alkenyl is optionally substituted with at least one substituent selected from R7;
• R5 is independently selected from:
• 1) hydrogen,
• 2) halogen,
• 3) —(CR1c2)nOR3,
• 4) —(CR1c2)nR6,
• 5) —C(O)OR3,
• 6) —C(O)R3,
• 7) —C≡CR3,
• 8) —R3C═C(R3)2,
• 9) —OS(O)mR6,
• 10) —NO2,
• 11) —(CR1c2)nN(R3)2,
• 12) —N(R3)C(O)R3,
• 13) —N(R3)S(O)mR6,
• 14) —(CR1c2)nNR3(CR1c2)nC(O)NR32,
• 15) —O(CR1c2)nC(O)N(R3)2,
• 16) —O(CR1c2)nC(O)OR3,
• 17) —NR3(CR1c2)nN(R3)2,
• 18) —(CR1c2)nNR3R6OR3,
• 19) —S(O)mR6,
• 20) —S(O)mN(R3)2,
• 21) —CN,
• 22) —(CR1c2)nN(R3)(CR1c2)nR6, and
• 23) —(CR1c2)nC(O)N(R3)2;
• R6 is independently selected from:
• 1) C1-C10 alkyl,
• 2) C3-C10 cycloalkyl,
• 3) aryl, and
• 4) heterocycle;
• said, alkyl, cycloalkyl, aryl and heterocycle is optionally substituted with at least one substituent selected from R7;
• R7 is independently selected from:
• 1) hydrogen,
• 2) unsubstituted or substituted C1-C10 alkyl,
• 3) unsubstituted or substituted C3-C10 cycloalkyl,
• 4) unsubstituted or substituted aryl,
• 5) halogen,
• 6) OR3,
• 7) CF3,
• 8) unsubstituted or substituted heterocycle,
• 9) S(O)mN(R3)2,
• 10) C(O)OR3,
• 11) C(O)R3,
• 12) CN,
• 13) C(O)N(R3)2,
• 14) N(R3)C(O)R3,
• 15) S(O)mR6, and
• 16) NO2;
• Y and Z are independently selected from:
• 1) hydrogen,
• 2) R6,
• 3) OR3,
• 4) N(R3)2,
• 5) C(O)OR3,
• 6) C(O)N(R3)2,
• 7) C(O)R3,
• 8) halogen,
• 9) N(R3)(CR1c2)nC(O)N(R3)2,
• 10) S(O)mN(R3)2,
• 11) N(R3)C(O)OR3,
• 12) N(R3)S(O)mR6,
• 13) N(R3)C(O)R3,
• 14) N(R3)(CR1c2)nR3,
• 15) S(O)mR6,
• 16) R6S(O)mN(R3)2,
• 17) R6S(O)mR6,
• 18) N(R3)S(O)m(CR1c2)nR6,
• 19) N(R3)S(O)mR6OR3,
• 20) N(R3)C(O)N(R3)2,
• 21) N(R3)C(O)R6OR3,
• 22) N(R3)(CR1c2)nR6OR3,
• 23) N(R3)OR3, and
• 24) N(R3)S(O)mR6NO2;
• m is independently 0, 1 or 2;
• n is independently 0 to 6;
• s is 0 to 6;
• t is 0 to 6;
• w is 0 to 4;
• or a pharmaceutically acceptable salt or stereoisomer thereof.