1. A pharmaceutical composition comprising an anti-cancer agent, an IGFR inhibitor represented by Formula I

I or a pharmaceutically acceptable salt thereof, wherein: Xi and X ₂ are each independently N or — C— (E') _aa ; X ₅ is N, -C-(E ¹ U or -N-(E ¹ U X ₃ , X ₄ , X ₆ , and X ₇ are each independently N or C; wherein at least one of X ₃ , X ₄ , X ₅ , X ₆ , and X ₇ is independently N or -N-(E') _aa ; Q ¹ is

X, ,, X ₁₂ , Xn, X.4, Xis, and X ₁₆ are each independently N, -C-(E ¹ V, or -N ⁺ -O ^" ; wherein at least one of X ₁₁ , X ₁₂ , X ₁₃ , X ₁₄ , Xi ₅ , and X ₁₆ is N or -N ⁺ -O ^' ;

R ¹ is absent, Coooalkyl, cycloC ₃ . ₁₀ a.kyl, bicycloC ₅ .i ₀ alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, heterobicycloC ₅ . ₁₀ alkyl, spiroalkyl, or heterospiroalkyl, any of which is optionally substituted by one or more independent G ¹¹ substituents;

E ¹ , E ¹ ', G ¹ , and G ⁴¹ are each independently halo, -CF ₃ , -OCF ₃ , -OR ² , -NR ² R ³ (R ^2a ) _j ,, -C(=O)R ² , -CO ₂ R ² , -CONR ² R ³ , -NO ₂ , -CN, -S(O)J ₁ R ² , -SO ₂ NR ² R ³ , -NR ² C(=O)R ³ , -NR ² C(=O)OR ³ , -NR ² C(=O)NR ³ R ^2a , -NR ² S(O) _j ,R ³ , -C(=S)OR ² , -C(=O)SR ² , -NR ² C(=NR ³ )NR ^2a R ^3a , -NR ² C(=NR ³ )OR ^2a , -NR ² C(=NR ³ )SR ^2a , -OC(O)OR ² , -OC(=O)NR ² R ³ , -OC(=O)SR ² , -SC(O)OR ² , -SC(O)NR ² R ³ , Co-ioalkyl, C ₂ .| _O alkenyl, C _2-U) alkynyl, C ₁ .i ₀ alkoxyC _2-1 oalkenyl, C ₍ . ₁₀ alkoxyC _2- ioalkynyl, Ci.ioalkylthioCj.ioalkyl, Ci.ioalkylthioC ₂ -ioalkynyl, cycloC ₃ . ₈ alkyl, cycloC _3-8 alkenyl, cycIoC ₃ . ₈ alkenylCi.]oalkyl, cycloC _3-8 alkylC _{2- l} oalkenyl, cycloC _3-8 alkenylC _2- ioalkenyl, cycloC _3-8 alkylC ₂ .ioalkynyl, cycloC ₃ . ₈ alkenylC _2- ιoalkynyl, heterocyclyl-Co-ioalkyl, heterocyclyl-C^oalkenyl, or heterocyclyl-C _2- ioalkynyl, any of which is optionally substituted with one or more independent halo, oxo, -CF ₃ , -OCF ₃ , -OR ²²² , -NR ²²² R ³³³ (R ^222a ) _jla , -C(=O)R ²²² , -CO ₂ R ²²² , -C(=O)NR ²²² R ³³³ , -NO ₂ , -CN, -S(=O) _jla R ²²² , -SO ₂ NR ²²² R ³³³ , -NR ²²² C(=O)R ³³³ , -NR ²²² C(=O)OR ³³³ , -NR ²²² C(=O)NR ³³³ R ^222a , -NR ²²² S(O) _jla R ³³³ , -C(=S)OR ²²² , -C(O)SR ²²² , -NR ²²² C(=NR ³³³ )NR ^222a R ^333β , -NR ²²² C(=NR ³³³ )OR ^222a ,

-NR ²²² C(=NR ³³³ )SR ²²² \ -OC(=O)OR ²²² , -OC(=O)NR ²²² R ³³ \ -OC(=O)SR ²²² , -SC(=O)OR ²²² _S or -SC(=O)NR ²²² R ³³³ substituents; or E ¹ , E", or G ¹ optionally is -CW%-(Y ^x ) _n -R ^A ; or E ¹ , E", G ¹ , or G ⁴¹ optionally independently is aryl-C^oalkyl, aryl-C ₂ .ioalkenyl, aryl-C ₂ . ₁₀ alkynyl, hetaryl-Q-ioalkyl, hetaryl-C ₂ -ioalkenyl, or hetaryl-C _2-10 alkynyl, any of which is optionally substituted with one or more independent halo, -CF ₃ , -OCF ₃ , -OR ²²² , -NR ²²² R ³³³ (R ^222a ) _j2a , -C(O)R ²²² , -CO ₂ R ²²² , -C(=O)NR ²²² R ³³³ , -NO ₂ , -CN, -S(O) _j2a R ²²² , -SO ₂ NR ²²² R ³³³ , -NR ²²² CC=O)R ³³³ , -NR ²²² CC=O)OR ³³³ , -NR ²²² C(=O)NR ³³³ R ^222a , -NR ²²² SCO) _j2a R ³³³ , -C(=S)OR ²²² , -CC=O)SR ²²² , -NR ²²² CC=NR ³³³ )NR ^222a R ³³³ \ -NR ²²² CC=NR ³³³ )OR ^222a , -NR ²²² CC=NR ³³³ )SR ^222a , -OCC=O)OR ²²² , -OCC=O)NR ²²² R ³³³ , -OC(=O)SR ²²² , -SCC=O)OR ²²² , or -SCC=O)NR ²²² R ³³³ substituents;

G" is halo, oxo, -CF ₃ , -OCF ₃ , -OR ²¹ , -NR ²¹ R ³¹ CR ²³ V -C(O)R ²¹ , -CO ₂ R ²¹ , -C(=O)NR ²¹ R ³¹ , -NO ₂ , -CN, -S(O) _J4 R ²¹ , -SO ₂ NR ²¹ R ³¹ , NR ²¹ (C=O)R ³¹ , NR ²¹ C(=O)OR ³¹ , NR ²¹ CC=O)NR ³ 'R ^2al , NR ²¹ S(O) _J4 R ³¹ , -CC=S)OR ²¹ , -CC=O)SR ²¹ , -NR ²¹ CC=NR ³ ^NR ²⁰¹ R ³¹ ", -NR ²¹ CC=NR ³ ^OR ²²¹ , -NR ²¹ C(=NR ³ ')SR ^2al , -OCC=O)OR ²¹ , -OCC=O)NR ²¹ R ³¹ , -OC(=O)SR ²¹ , -SCC=O)OR ²¹ , -SCC=O)NR ²¹ R ³¹ , -P(O)OR ²¹ OR ³¹ , C,.,oalkyhdene, Ccoalkyl, C _2- ,oalkenyl, C _2-l0 alkynyl, C.oalkoxyC,. _l oalkyl, C|.ιoalkoxyC ₂ .ioalkynyl, Ci _-l0 alkylthioC ₂ . _l oalkenyl, C _M oalkylthioC ₂ -ioalkynyl, cycloC ₃ . ₈ alkyl, cycloC ₃ . ₈ alkenyl, cycloC ₃ .galkylCi.ioalkyl, cycloC _3- galkenylCi.ioalkyl, cycloC ₃ . ₈ alkylC _2- ioalkenyl, cycloC ₃ . _g alkenylC _2- ι ₀ alkenyl, cycloC ₃ .galkylC _2- i ₀ alkynyl, cycloC ₃ .galkenylC ₂ .ioalkynyl, heterocyclyl-Co-ioalkyl, or heterocyclyl— C ₂ . _l oalkynyl, any of which is optionally substituted with one or more independent halo, oxo, -CF ₃ , -OCF ₃ , -OR ²²²¹ , -NR ²²²¹ R ³³³¹ CR ^222aI ) _j4 a, -CCO)R ²²²¹ , -CO ₂ R ²²²¹ , -C(=O)NR ²²²¹ R ³³³¹ , -NO ₂ , -CN, -SCO) _j4a R ²²²¹ , -SO ₂ NR ²²²¹ R ³³³¹ , -NR ²²²¹ CC=O)R ³³³¹ , -NR ²²²¹ CC=O)OR ³³³¹ , -NR ²²²¹ CC=O)NR ³³³¹ R ²²² * ¹ , -NR ^222l S(O) _j4a R ³³³¹ , -CC=S)OR ²²²¹ , -C(=O)SR ²²²¹ , -NR ²²²¹ C(=NR ³³³¹ )NR ^222al R ^333al , -NR ²²² 'CC=NR ³³³¹ )OR ^222al , -NR ²²²¹ CC=NR ³³³¹ )SR ^222al , -OC(=O)OR ²²²¹ , -OCC=O)NR ²²²¹ R ³³³¹ , -OCC=O)SR ²²²¹ , -SCC=O)OR ²²²¹ , -PCO)OR ²²²¹ OR ³³³¹ , Or -SCC=O)NR ²²²¹ R ³³³¹ substituents; or G" is aryl-Ccioalkyl, aryl-C ₂ .ioalkenyl, aryl-C _2- ] _O alkynyl, hetaryl-Co-ioalkyl, hetaryl-C ₂ . _l oalkenyl, or hetaryl-C _2-10 alkynyl, any of which is optionally substituted with one or more independent halo, -CF ₃ , -OCF ₃ , -OR ²²²¹ , -NR ²²²¹ R ³³³¹ (R ^222al ) _j5a , -C(O)R ²²²¹ , -CO ₂ R ²²²¹ , -CC=O)NR ²²²¹ R ³³³¹ , -NO ₂ , -CN, -S(O) _j5a R ²²²¹ , -SO ₂ NR ²²²¹ R ³³³¹ , -NR ²²²¹ CC=O)R ³³³¹ , -NR ²²²¹ CC=O)OR ³³³¹ , -NR ²²²¹ CC=O)NR ³³³¹ R ²²²³¹ , -NR ²²²¹ SCO) _j5a R ³³³¹ , -C(=S)OR ²²² \ -C(=O)SR ²²²¹ , -NR ^222l CC=NR ³³³¹ )NR ^222al R ^333al , -NR ²²²¹ C(=NR ³³³¹ )OR ^222al , -NR ²²²¹ CC=NR ³³³¹ )SR ^222al , -OCC=O)OR ²²²¹ , -OCC=O)NR ²²²¹ R ³³³¹ , -OC(=O)SR ²²²¹ , -SCC=O)OR ²²²¹ , -PCO)OR ²²²¹ OR ³³³¹ , or -SCC=O)NR ²²²¹ R ³³³¹ substituents; or G" is C, taken together with the carbon to which it is attached forms a C=C double bond which is substituted with R ⁵ and G ¹ ";

R ² , R ^2a , R ³ , R ^3a , R ²²² , R ^222a , R ³³³ , R ^333a , R ²¹ , R ^2al , R ³¹ , R ^3al , R ²²²¹ , R ^222al , R ³³³¹ , and R ^333al are each independently Co-ioalkyl, C ₂ _ioalkenyl, C ₂ -ioalkynyl, Ci _-)0 alkoxyC).ioalkyl, Ci.ιoalkoxyC _2- ioalkenyl, C,. i ₀ alkoxyC ₂ .ioalkynyl, Ci.ioalkylthioCi.ioalkyl, Ci. ₁₀ alkylthioC ₂ .ioalkynyl, cycloC ₃ . ₈ alkyl, cycloC ₃ _ ₈ alkenyl, cycloCs-galkylC _M oalkyl, cycloC ₃ . ₈ alkenylCi,]oalkyl, cycloC _3-8 alkylC ₂ . _l oalkenyl, cycloC ₃ . ₈ alkenylC ₂ .ioalkenyl, cycloC ₃ . ₈ alkylC ₂ .ioalkynyl, cycloC ₃ . ₈ alkenylC _2- ιoalkynyl, heterocyclyl-Co.ioalkyl, heterocyclyl— C _2- ιoalkenyl, heterocyclyl-C _2- i ₀ alkynyl, aryl-Qμioalkyl, aryl-C _{2- l} oalkenyl, aryl— C ₂ .i ₀ alkynyl, hetaryl— Co-ioalkyl, hetaryl-C _2- ioalkenyl, or hetaryl-C2-ioalkynyl, any of which is optionally substituted by one or more independent G ¹ ' ' substituents; or in the case of -NR ² R ³ (R ^2a ) _j , or -NR ²²² R ³³³ (R ^222a ) _jla or -NR ²²² R ³³³ (R ^222a ) _j2a or -NR ²¹ R ³¹ (R ^2al ) _j4 or -NR ²²²¹ R ^333l (R ^222a) ) _j4a or -NR ²²²¹ R ³³³¹ (R ^222al ) _j5a , then R ² and R ³ , or R ²²² and R ³³³ , or R ²²²¹ and R ³³³¹ , respectfully, are optionally taken together with the nitrogen atom to which they are attached to form a 3- 10 membered saturated or unsaturated ring, wherein said ring is optionally substituted by one or more independent G ¹ " ¹ substituents and wherein said ring optionally includes one or more heteroatoms other than the nitrogen to which R ² and R ³ , or R ²²² and R ³³³ , or R ²²²¹ and R ³³³¹ are attached;

W ¹ and Y ¹ are each independently -O-, -NR ⁷ -, -S(O) _j7 -, -CR ⁵ R ⁶ -, -N(C(O)OR ⁷ )-, -N(C(O)R ⁷ )-, -N(SO ₂ R ⁷ )-, -CH ₂ O-, -CH ₂ S-, -CH ₂ N(R ⁷ )-, -CH(NR ⁷ )-, -CH ₂ N(C(O)R ⁷ )-, -CH ₂ N(C(O)OR ⁷ )-, -CH ₂ N(SO ₂ R ⁷ )-, -CH(NHR ⁷ )-, -CH(NHC(O)R ⁷ )-, -CH(NHSO ₂ R ⁷ )-, -CH(NHC(O)OR ⁷ )-, -CH(OC(O)R ⁷ )-, -CH(OC(O)NHR ⁷ )-, -CH=CH-, -C≡C-, -C(=NOR ⁷ )-, -C(O)-, -CH(OR ⁷ )-, -C(O)N(R ⁷ )-, -N(R ⁷ )C(O)-, -N(R ⁷ )S(O)-, -N(R ⁷ )S(O) ₂ - -OC(O)N(R ⁷ )-, -N(R ⁷ )C(O)N(R ⁸ )-, -NR ⁷ C(O)O-, -S(O)N(R ⁷ )-, -S(O) ₂ N(R ⁷ )-, -N(C(O)R ⁷ )S(O)-, -N(C(O)R ⁷ )S(O) ₂ -, -N(R ⁷ )S(O)N(R ⁸ )-, -N(R ⁷ )S(O) ₂ N(R ⁸ )-, -C(O)N(R ⁷ )C(O)-, -S(O)N(R ⁷ )C(O)-, -S(O) ₂ N(R ⁷ )C(O)-, -OS(O)N(R ⁷ )-, -OS(O) ₂ N(R ⁷ )-, -N(R ⁷ )S(O)O-, -N(R ⁷ )S(O) ₂ O-, -N(R ⁷ )S(O)C(O)-, -N(R ⁷ )S(O) ₂ C(O)-, -SON(C(O)R ⁷ )-, -SO ₂ N(C(O)R ⁷ )-, -N(R ⁷ )SON(R ⁸ )-, -N(R^SO ₂ N(R ⁸ )-, -C(O)O-, -N(R ⁷ )P(OR ⁸ )O-, -N(R ⁷ )P(OR ⁸ )-, -N(R ⁷ )P(O)(OR ⁸ )O-, -N(R ⁷ )P(O)(OR ⁸ )-, -N(C(O)R ⁷ )P(OR ⁸ )O-, -N(C(O)R ⁷ )P(OR ⁸ )-, -N(C(O)R ⁷ )P(O)(OR ⁸ )O-, -N(C(O)R ⁷ )P(OR ⁸ )-, -CH(R ⁷ )S(O)-, -CH(R ⁷ )S(O) ₂ -, -CH(R ⁷ )N(C(O)OR ⁸ )-, -CH(R ⁷ )N(C(O)R ⁸ )-, -CH(R ⁷ )N(SO ₂ R ⁸ )- ₎ -CH(R ⁷ )O-, -CH(R ⁷ )S-, -CH(R ⁷ )N(R ⁸ )-, -CH(R ⁷ )N(C(O)R ⁸ )-, -CH(R ⁷ )N(C(O)OR ⁸ )-, -CH(R ⁷ )N(SO ₂ R ⁸ )-, -CH(R ⁷ )C(=NOR ⁸ )-, -CH(R ⁷ )C(O)-, -CH(R ⁷ )CH(OR ⁸ )-, -CH(R ⁷ )C(O)N(R ⁸ )-, -CH(R ⁷ )N(R ⁸ )C(O)-, -CH(R ⁷ )N(R ⁸ )S(O)-, -CH(R ⁷ )N(R ⁸ )S(O) ₂ -, -CH(R ⁷ )OC(O)N(R ⁸ )-, -CH(R ⁷ )N(R ⁸ )C(O)N(R ^7a K -CH(R ⁷ )NR ⁸ C(O)O-, -CH(R ⁷ )S(O)N(R ⁸ )-, -CH(R ⁷ )S(O) ₂ N(R ⁸ )-, -CH(R ⁷ )N(C(O)R ⁸ )S(0)-, -CH(R ⁷ )N(C(0)R ⁸ )S(0)-, -CH(R ⁷ )N(R ⁸ )S(O)N(R ^7a )-, -CH(R ⁷ )N(R ⁸ )S(O) ₂ N(R ^7a )-, -CH(R ⁷ )C(O)N(R ⁸ )C(O)-, -CH(R ⁷ )S(O)N(R ⁸ )C(O)-, -CH(R ⁷ )S(O) ₂ N(R ⁸ )C(O)-, -CH(R ⁷ )OS(O)N(R ⁸ )-, -CH(R ⁷ )OS(O) ₂ N(R ⁸ )-. -CH(R ⁷ )N(R ⁸ )S(O)O-, -CH(R ⁷ )N(R ⁸ )S(O) ₂ O-, -CH(R ⁷ )N(R ⁸ )S(O)C(O)-, -CH(R ⁷ )N(R ⁸ )S(O) ₂ C(O)-, -CH(R ⁷ )SON(C(O)R ⁸ )-, -CH(R ⁷ )SO ₂ N(C(O)R ⁸ )-, -CH(R ⁷ )N(R ⁸ )SON(R ^7a )-, -CH(R ⁷ )N(R ⁸ )SO ₂ N(R ^7a )-, -CH(R ⁷ )C(O)O-, -CH(R ⁷ )N(R ⁸ )P(OR ^7a )O-, -CH(R ⁷ )N(R ⁸ )P(OR ^7a )-,

-CH(R ⁷ )N(R ⁸ )P(0)(OR ^7a )0-, -CH(R ⁷ )N(R ⁸ )P(0)(0R ^7a )-, -CH(R ⁷ )N(C(O)R ⁸ )P(OR ^7a )0-, -CH(R ⁷ )N(C(O)R ⁸ )P(OR ^7a )-, -CH(R ⁷ )N(C(O)R ⁸ )P(O)(OR ^7a )O- or -CH(R ⁷ )N(C(O)R ⁸ )P(OR ^7a )-;

R ⁵ , R ⁶ , G ^m , andG"" are each independently Co-ioalkyl, C _2- , _o alkenyl, C _2-10 alkynyl, Ci-ioalkoxyCi.ioalkyl, Ci.ioalkoxyC _2- ioalkenyl, Ci.,oalkoxyC _2- ioalkynyU Ci.ιoalkylthioC,.,oalkyl, C ₁ . ₎₀ alkylthioC _2- i ₀ alkenyl, Ci.| ₀ alkylthioC ₂ .ioalkynyl, cycloC ₃ _ ₈ alkyl, cycloC ₃ . ₈ alkenyl, cycloC ₃ . ₈ alkylCi. ₁₀ alkyl, cycloC _3-8 alkenylCi_| ₀ alkyl, cycloC ₃ . ₈ alkylC ₂ . ₁₀ alkenyl, cycloC _3-8 alkenylC ₂ . ₁₍ )alkenyl, CyCIoC ₃ . ₈ alkylC _2- ,oalkynyl, cycloC _3-8 alkenylC ₂ .ioalkynyl, heterocyclyl-Co-ioalkyl, heterocyclyl-C ₂ .ιoalkenyl, heterocyclyl-Cj.ioalkynyl, aryl-Co-ioalkyl, aryl-C ₂ .i _O alkenyl, aryl-C _2-) oalkynyl, hetaryl-Co.ιoalkyl, hetaryl— C ₂ .ioalkenyl, or hetaryl-C _2- ι ₀ alkynyl, any of which is optionally substituted with one or more independent halo, -CF ₃ , -OCF ₃ , -OR ⁷⁷ , -NR ⁷⁷ R ⁸⁷ , -C(O)R ⁷⁷ , -CO ₂ R ⁷⁷ , -CONR ⁷⁷ R ⁸⁷ , -NO ₂ , -CN, -S(O) _j5a R ⁷⁷ , -SO ₂ NR ⁷⁷ R ⁸⁷ , -NR ⁷⁷ CC=O)R ⁸⁷ , -NR ⁷⁷ C(=O)OR ⁸⁷ , -NR ⁷⁷ CC=O)NR ⁷⁸ R ⁸⁷ , -NR ⁷⁷ S(O) _j5a R ⁸⁷ , -C(=S)OR ⁷⁷ , -CC=O)SR ⁷⁷ , -NR ⁷⁷ C(=NR ⁸⁷ )NR ⁷⁸ R ⁸⁸ , -NR ⁷⁷ C(=NR ⁸⁷ )OR ⁷⁸ , -NR ⁷⁷ CC=NR ⁸⁷ )SR ⁷⁸ , -OCC=O)OR ⁷⁷ , -OCC=O)NR ⁷⁷ R ⁸⁷ , -OC(=O)SR ⁷⁷ , -SC(=O)OR ⁷⁷ , -PCO)OR ⁷⁷ OR ⁸⁷ , or -SC(=O)NR ⁷⁷ R ⁸⁷ substituents; or R ⁵ with R ⁶ are optionally taken together with the carbon atom to which they are attached to form a 3-10 membered saturated or unsaturated ring, wherein said ring is optionally substituted with one or more independent R ⁶⁹ substituents and wherein said ring optionally includes one or more heteroatoms;

R ⁷ , R ^7a , and R ⁸ are each independently acyl, Co_ioalkyl, C _2- ioalkenyl, aryl, heteroaryl, heterocyclyl or cycloC ₃ .ioalkyl, any of which is optionally substituted by one or more independent G ¹ " substituents;

R ⁴ is Co-ioalkyl, C ₂ .ioalkenyl, C ₂ _ioalkynyl, aryl, heteroaryl, cycloC ₃ _i ₀ alkyl, heterocyclyl, cycloGj. ₈ alkenyl, or heterocycloalkenyl, any of which is optionally substituted by one or more independent G ⁴¹ substituents;

R ⁶⁹ is halo, -OR ⁷⁸ , -SH, -NR ⁷⁸ R ⁸⁸ , -CO ₂ R ⁷⁸ , -CC=O)NR ⁷⁸ R ⁸⁸ , -NO ₂ , -CN, -S(O) _j8 R ⁷⁸ , -SO ₂ NR ⁷⁸ R ⁸⁸ , Co-ioalkyl, C ₂ .ιoalkenyl, C ₂ . _l0 alkynyl, C,.,oalkoxyC _M0 alkyl, C,. ₁₀ alkoxyC ₂ .ioalkenyl, C _1- ι ₀ alkoxyC _2- ioalkynyl, Ci.ioalkylthioCi.ioalkyl, Ci.ioalkylthioC _2- i ₀ alkynyl, cycloC ₃ . ₈ alkyl, cycloC ₃ _ ₈ alkenyl, cycloC _3-8 alkenylCi-i ₀ alkyl, cycloC ₃ . ₈ alkylC ₂ . _)O alkenyl, cycloC ₃ . ₈ alkenylC _2- i ₀ alkenyl, cycloC ₃ . ₈ alkylC ₂ _i ₀ alkynyl, cycloC ₃ . ₈ alkenylC ₂ .ioalkynyl, heterocyclyl-Co-ioalkyl, heterocyclyl-C ₂ _ _I0 alkenyl, or heterocyclyl-C _2- ioalkynyl, any of which is optionally substituted with one or more independent halo, cyano, nitro, -OR ⁷⁷⁸ , -SO ₂ NR ⁷⁷⁸ R ⁸⁸⁸ , or -NR ⁷⁷⁸ R ⁸⁸⁸ substituents; or R ⁶⁹ is aryl-Co-ioalkyl, aryl-C ₂ .| ₀ alkenyl, aryl-C _2- i ₀ alkynyl, hetaryl-Co.i _O alkyl, hetaryl-C ₂ . _l oalkenyl, hetaryl-C ₂ .,oalkynyl, di(C _]-6 alkyl)ammoCi. ₆ alkyl, monoCaryl)aminoCi.6alkyl, any of which is optionally substituted with one or more independent halo, cyano, nitro, -OR ⁷⁷⁸ , Ci.i _O alkyl, C _2- i _O alkenyl, Q.ioalkynyl, haloC _MO alkyl, haloC ₂ .ιoalkenyl, haloC _2-10 alkynyl, -COOH, C _1-4 alkoxycarbonyl, -CC=O)NR ⁷⁷⁸ R ⁸⁸⁸ , -SO ₂ NR ⁷⁷⁸ R ⁸⁸⁸ , or -NR ⁷⁷⁸ R ⁸⁸⁸ substituents;

or in the case Of-NR ⁷⁸ R ⁸⁸ , R ⁷⁸ and R ⁸⁸ are optionally taken together with the nitrogen atom to which they are attached to form a 3-10 membered saturated or unsaturated ring, wherein said ring is optionally substituted with one or more independent halo, cyano, hydroxy, nitro, C|.|oalkoxy, -SO ₂ NR R , or -NR R substituents, and wherein said ring optionally includes one or more heteroatoms other than the nitrogen to which R ⁷⁸ and R ⁸⁸ are attached;

R ⁷⁷ , R ⁷⁸ , R ⁸⁷ , R ⁸⁸ , R ⁷⁷⁸ , and R ⁸⁸⁸ are each independently Co-i ₀ alkyl, C _2- i _O alkenyl, C ₂ .i _O alkynyl, C ₁ . _l oalkoxyCi.ioalkyl, C|.ιoalkoxyC _2- ioalkenyl, Ci.ιoalkoxyC ₂ .ioalkynyl, C _1- i ₀ alkylthioC _2- i ₀ alkenyl, Ci.ioalkylthioC ₂ .ioalkynyl, cycloC _3-8 alkyl, cycloC _3-8 alkenyl, cycloC _3- galkylCi. _l oalkyl, cycloC ₃ . ₈ alkenylCi.ioalkyl, cycloC ₃ . _g alkylC _M oalkenyl, cycloC ₃ _ _g alkenylC ₂ .ioalkenyl, cycloC ₃ . ₈ alkylC ₂ .i _O alkynyl, cycloC ₃ . ₈ alkenylC ₂ _ioalkynyl, heterocyclyl-Co-ioalkyl, heterocyc IyI-C ₂ . ₁₀ alkenyl, heterocyclyl-C _2-10 alkynyl, Ci _-10 alkylcarbonyl, C ₂ .ioalkenylcarbonyl, C ₂ .ιoalkynylcarbonyl, Q- ₎₀ alkoxycarbonyl, Ci.ioalkoxycarbonylCi.ioalkyl, monoC^alkylaminocarbonyl, diCi.βalkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl _? or

Ci.i ₀ alkyl(aryl)aminocarbonyl, any of which is optionally substituted with one or more independent halo, cyano, hydroxy, nitro, Q.ioalkoxy, -S0 ₂ N(C( _M alkyl)(Co_ ₄ alkyl), or -N(Co- ₄ alkyl)(Co- ₄ alkyl) substituents; or R ⁷⁷ , R ⁷⁸ , R ⁸⁷ , R ⁸⁸ , R ⁷⁷⁸ , and R ⁸⁸⁸ are each independently aryl-Co-ioalkyl, aryl-C ₂ .i ₀ alkenyl, aryl-C ₂ -ioalkynyl, hetaryl-Co-ioalkyl, hetaryl-C _2- ioalkenyl, hetaryl-C ₂ .| _O alkynyl, di(aryl)aminoC|. ₆ alkyl, or any of which is optionally substituted with one or more independent halo, cyano, nitro, -O(C( _M alkyl), C _MO alkyl, C _2- ioalkenyl, C ₂ _ioalkynyl, haloCf.ioalkyl, haloCz.ioalkenyl, haloC ₂ .ioalkynyl, -COOH, C^alkoxycarbonyl, -CON(Co- ₄ alkyl)(C _0- ioalkyl), -S0 ₂ N(Co-4alkyl)(QMalkyl), or -N(CcMalkyl)(Co-4alkyl) substituents; n, m, j 1, jla, j2a, j4, j4a, j5a, j7, and j8 are each independently 0, 1, or 2; and aa and bb are each independently 0 or 1 ; and a pharmaceutically acceptable carrier.

2. The pharmaceutical composition of claim 1 wherein the IGFR inhibitor is represented by Formula I

I or a pharmaceutically acceptable salt thereof, wherein: Xi, X ₂ , X4, Xe. and X7 are C; X ₃ and X ₅ are N;

Xi i, X|2, Xi3, Xi4, and Xi ₅ are C;

X ₁₆ is N; and

R ¹ is cycloC ₃ _ ₁₀ alkyl optionally substituted by one or more independent G" substituents.

3. A pharmaceutical composition comprising an anti-cancer agent, a pharmaceutically acceptable carrier, and an IGFR inhibitor selected from the group consisting of: 3-Cyclobutyl-l-(2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine; S-Cyclobutyl-l-ζZ-thiophen-Z-ylquinolin-7-yty-imidazotl.S-aføyrazin-S-ylamine; 3-Cyclobutyl-l-(2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine; ^-(S-Amino-S-cyclobutylimidazotl.S-ajpyrazin-l-yty-quinolin-2-ylJ-phenylamine; l-(6-Chloro-2-phenylquinolin-7-yl)-3-cyclobutylimidazo[l,5-a]pyrazin-8-ylamine; l-(6-Chloro-2-pyridin-2-ylquinolin-7-yl)-3-cyclobutylimidazo[l,5-a]pyrazin-8-ylamine; l^ό-Chloro^-thiophen-2-ylquinolin^-yl^-cyclobutylimidazofl.S-aJpyrazin-S-ylamine; l-(6-Chloro-2-phenoxyquinolin-7-yl)-3-cyclobutylimidazo[l,5-a]pyrazin-8-ylamine; [7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l-yl)-6-chloroquinolin-2-yl]-phenyl-amine; S-Cyclobutyl-l-Cδ-fluoro-Z-phenylquinolin-2-yO-imidazotl.S-alpyrazin-δ-ylamine; S-Cyclobutyl-l-Cδ-fluoro^-pyridin-2-ylquinolin^-y^-imidazofl.S-aJpyrazin-S-ylamine; S-Cyclobutyl-l^S-fluoro^-thiophen^-ylquinolin^-y^-imidazofl.S-aJpyrazin-δ-ylamine; S-Cyclobutyl-l-CS-fluoro^-phenoxyquinolin^-y^-imidazotl.S-alpyrazin-δ-ylamine; [7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l-yl)-8-fluoroquinolin-2-yl]-phenyl-amine; 3-Cyclobutyl-l -(4-methyl-2-phenylquinolin-7-yl)-imidazo[l ,5-a]pyrazin-8-ylamine; S-Cyclobutyl-l^-methyl^-pyridin-2-ylquinolin^-y^-imidazotl^-alpyrazin-S-ylamine; S-Cyclobutyl-l ^-methyl^-thiophen-2-ylquinolin^-y^-imidazotl.S-ajpyrazin-S-ylamine; [7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l-yl)-4-methylquinolin-2-yl]-phenylamine; S-Cyclobutyl-l^-methyl^-phenoxyquinolin^-y^-imidazofl.S-aJpyrazin-S-ylamine; [7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l-yl)-2-phenylquinolin-4-yl]-methylamine; [7-(8-Amino-3-cyclobutylimidazo[ 1 ,5-a]pyrazin- 1 -yl)-2-pyridin-2-ylquinolin-4-yl]-methylamine; [7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l-yl)-2-thiophen-2-ylquinolin-4-yl]-methylamine; [7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l-yl)-2-phenoxyquinolin-4-yl]-methylamine; 7-(8-Amino-3-cyclobutylimidazo[l,5-α]pyrazin-l-yl)-λ' ⁴ -methyl-N ² -phenylquinoline-2 ₎ 4-diamine; 3-[8-Amino-l-(2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol; 3-[8-Amino-l -(2-thiophen-2-ylquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-3-yl]-cyclobutanol; 3-[8-Amino-l -(2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol; 3-[8-Amino-l -(2-phenylaminoquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(6-chloro-2-pheny1quinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(6-chloro-2-phenylaminoquinolin-7-yl)-imidazotl,5-a]pyrazin-3-yl]-cyclobutanol;

S-JS-Amino-l^o-chloro^-phenoxyquinolin-y-yO-imidazofl _j S-aJpyrazin-S-ylJ-cyclobutanol;

S-IS-Amino-l-CS-fluoro^-pyridin-2-ylquinolin-y-y^-imidazotl.S-alpyrazin-S-y^-cyclobutanol;

3-[8-Amino-l-(8-fluoro-2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(8-fluoro-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino- 1 -(8-fluoro-2-phenylaminoquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-3 -yl]-cyclobutanol;

3-[8-Amino-l-(8-fluoro-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(8-fluoro-4-methyl-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(8-fluoro-4-methyl-2-thiophen-2-yl-quinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclobutanol;

3-[8-Amino-l-(8-fluoro-4-methyl-2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclobutanol;

3-[8-Amino-l-(8-fluoro-4-methyl-2-phenyIaminoquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclobutanol;

3-[8-Amino-l-(8-fluoro-4-methyl-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-(3-Azetidin-l -ylmethylcyclobutyl)-l -(2-pyridin-2-ylquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-8-ylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

S-P-Azetidin-l-ylmethylcyclobutyO-l-^φhenoxyquinolin^-yty-imidazoP.S-aJpyrazin-δ-ylamine;

{7-[8-Amino-3-(3-azetidin-l-ylmethylcyclobutyl)-imidazo[l ,5-a]pyrazin-l -yl]-quinolin-2-yl } - phenylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(6-chloro-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(6-chloro-2-pyridin-2-yl-quinolin-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(6-chloro-2-thiophen-2-yl-quinolin-7-yl)-imidazo[l,5-a]pyrazin-

8-ylamine;

{7-[8-Amino-3-(3-azetidin-l-ylmethylcyclobutyl)-imidazo[l,5-a]pyrazin-l-yl]-6-chloro-quinolin-2-yl}- phenylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(6-chloro-2-phenoxyquinolin-7-yl)-imidazofl ,5-a]pyrazin-8- ylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(4-methyl-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

S-CS-Azetidin-l-ylmethylcyclobutyO-l^-methyl^-pyridin-2-ylquinolin-y-yO-imidazotljS-aJpyrazin-S- ylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(4-methyl-2-thiophen-2-ylquinohn-7-yl)-imidazo[l,5-a]pyrazin-

8-ylamine,

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(4-methyl-2-phenoxyquinolm-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

{7-[8-Amino-3-(3-azetidin-l-ylmethylcyclobutyl)-imidazo[l,5-a]pyrazin-l-yl]-4-methyl-quinolin-2-yl}- phenyl -amine,

3-(3-Dimethylaminomethylcyclobutyl)-l-(2-ρhenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine,

3-(3-Dimethylammomethylcyclobutyl)-l-(2-pyndin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

3-(3-Dimethylaminoτnethylcyclobutyl)-l-(2-thiophen-2-ylquinohn-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

{7-[8-Amino-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l,5-a]pyrazin-l-yl]-quinolin-2-yl}- phenylamine,

3-(3-Dimethylaminomethylcyclobutyl)-l-(2-pheπoxyqumohn-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine, l-(6-Chloro-2-phenylqumolin-7-yl)-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l,5-a]pyrazm-8- ylamine; l-(6-Chloro-2-pyndin-2-ylquinolin-7-yl)-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l,5-a]pyrazin-

8-ylamine, l -(6-Chloro-2-thiophen-2-ylquinohn-7-y])-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l ,5-a]pyrazin-

8-ylamine; l -(6-Chloro-2-phenoxyquinohn-7-yl)-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l,5-a]pyrazin-8- ylamine,

{7-[8-Amino-3-(3-dimethylaminomethylcyclobutyl)-imidazo[ 1 ,5-a]pyrazm-l -yl]-6-chloroquinohn-2-yl } - phenylamme,

3-(3-Dimethylaminomethylcyclobutyl)-l-(4-methyl-2-phenylqumolin-7-y])-imidazo[l,5-a]pyrazin-8- ylamine,

S-CS-DimethylaminomethylcyclobutyO-l^-methyl^-pyridin-2-ylquinolm^-y^-imidazofl.S-ajpyrazin-

8-ylamine,

3-(3-Dimethylaminomethylcyclobutyl)-l-(4-methyl-2-thiophen-2-ylquinohn-7-yl)-imidazo[l,5- a]pyrazin-8-ylamme;

{7-[8-Ammo-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l,5-a]pyrazin-l-yl]-4-methylquinohn-2- yl}-phenylamine;

S^S-DimethylaminomethylcyclobutylJ-l^-methyl^-phenoxyquiπohn^-yO-imidazofl.S-alpyrazin-S- ylamine,

4-[8-Amino-l -(2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxyhc acid amide;

4-[8-Amino-l-(2-thiophen-2-ylquinohn-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxyhc acid amide;

4-[8-Amino-l -(2-ρhenoxyquinohn-7-yl)-imidazo[l ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide,

4-[8-Aτnino-l-(2-phenylaminoquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino- 1 -(6-chloro-2-phenylquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(6-chloro-2-phenylaminoquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(6-chloro-2-phenoxyquinolin-7-yl)-imidazo[l ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(4-methyl-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(4-methyl-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(4-methy]-2-phenylaminoquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylamide;

4-[8-Amino-l -(2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylamide;

4-[8-Amino-l-(2-phenylaminoquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylamide;

4-[8-Amino-l -(2-phenoxyquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylamide;

S^-Aminomethylcyclohexy^-l ^-pyridin-2-ylquinolin^-y^-imidazotl.S^pyrazin-S-ylamine;

3-(4-Aminomethylcyclohexyl)-l-(2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

3-(4-Aminomethylcyclohexy1)-l -(2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-y1amine;

{7-[8-Amino-3-(4-aminomethylcyclohexyl)-imidazo[l,5-a]pyrazin-l-yl]-quinolin-2-yl}-phenylamine;

7<Iyclobutyl-5-(2φhenylquinolin-7-yl)-7Hφyrrolo[2,3^]pyrimidin^-ylamine;

7-Cyclobutyl-5-(2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin^4-ylamine;

7-Cyclobutyl-5-(2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

[7-(4-Amino-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-quinolin-2-yl]-phenylamine;

7-Cyclobutyl-5-(2-phenoxyquinolin-7-yl)-7H-pyrrolo[2 _> 3-d]pyrimidin-4-ylamine;

5-(6-Chloro-2-phenylquinohn-7-yl)-7-cyclobutyl-7H-pyrrolo[2,3-d]pynmidin-4-ylamme;

5-(6-Chloro-2-pyridm-2-ylquinolin-7-yl)-7-cyclobutyl-7H-pyrrolo[2,3-d]pynnndin-4-ylamine;

5-(6-Chloro-2-thiophen-2-ylquinolin-7-yl)-7-cyclobutyl-7H-pyrrolo[2,3-d]pyπmidin-4-ylamine;

5-(6-Chloro-2-phenoxyquinolin-7-yl)-7-cyclobutyl-7H-pyττolo[2,3-d]pynmidm-4-ylamine;

[7-(4-Amino-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-6-chloroquinolin-2-yl]-phenylamine;

3-[4-Amino-5-(2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Aτnino-5-(2-thiophen-2-ylquinolin-7-yl)-pyτrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol,

3-[4-Ammo-5-(2-pyndin-2-ylquinohn-7-yl)-pyrrolo[2,3-d]pyπmidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(2-phenylaminoquinolm-7-yl)-pyrrolo[2,3-d]pyriπiidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(2-phenoxyquinolm-7-yl)-pyrrolo[2,3-d]pyπmidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(6-chloro-2-pyridin-2-ylquinohn-7-yl)-pyrrolo[2,3-d]pynmidin-7-yl]-cyclobutanol,

3-[4-Amino-5-(6-chloro-2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyπmidin-7-yl]-cyclobutanol;

3 -[4-Aπuno-5 -(6-chloro-2-thiophen-2-ylquιnohn-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl] -cyclobutanol,

3-[4-Ammo-5-(6-chloro-2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyπmidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(6-chloro-2-phenylaminoqumohn-7-yl)-pyrrolo[2,3-d]pyrimidm-7-yl]-cyclobutanol,

3-[4-Amino-5-(8-fluoro-2-phenylqumolm-7-yl)-pyrrolo[2,3-d]pyπmidm-7-yl]-cyclobutanol;

3-[4-Ammo-5-(8-fluoro-2-thiophen-2-ylqumolin-7-yl)-pyrrolo[2,3-d]pyπmidin-7-yl]-cyclobutanol,

3-[4-Ammo-5-(8-fluoro-2-pyπdin-2-ylquinohn-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol,

3-[4-Amino-5-(8-fluoro-2-phenylaminoquinohn-7-yl)-pyrrolo[2,3-d]pyrimidm-7-yl]-cyclobutanol,

3-[4-Amino-5-(8-fluoro-2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyπmidin-7-yl]-cyclobutanol,

7-Cyclobutyl-5-(8-fluoro-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyπinidin-4-ylamine,

7-Cyclobυtyl-5-(8-fluoro-2-pyndin-2-ylquinohn-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylanime;

7-Cyclobutyl-5-(8-fluoro-2-thiophen-2-yl-quinolm-7-yl)-7H-pyττolo[2,3-d]pyπmidm-4-ylamine,

7-Cyclobutyl-5-(8-fluoro-2-phenoxyquinohn-7-yl)-7H-pyrrolo[2,3-d]pynmidin-4-ylamine;

[7-(4-Amino-7-cyclobutyl-7H-pyrrolo[2,3-d]pynmidin-5-yl)-8-fluoroqutnohn-2-yl]-phenylamine;

7-(3-Azetidin-l-y]methylcyclobutyl)-5-(2-phenylquinohn-7-yl)-7H-pyπOlo[2,3-d]pyπmidin-4-ylamine;

7-(3-Azetidin-l -ylmethylcyclobutyl)-5-(2-pyπdin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyπmidin-4- ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-thiophen-2-yl-quinolin-7-yl)-7H-pyrrolo[2,3-d]pynmidin-4- ylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]ρyrimidin-5-yl]-quinohn-2-yl}- phenylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-phenoxyquinohn-7-yl)-7H-pyrrolo[2,3-d]pyπmidin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(6-chloro-2-pyridin-2-ylquinohn-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(6-chloro-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyπmidin-4- ylamine,

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(6-chloro-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyriτnidin-

4-ylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyπmidin-5-yl]-6-chloroquinolin-2- yl} -phenylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(8-fluoro-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-7H-pyrτolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(8-fluoro-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyriinidin-5-yl]-8-fluoroquinolin-2- yl } -phenyl-amine;

7-(3-Azetidin-l -ylmethylcyclobutyl)-5-(8-fluoro-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-

4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(4-methyl-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(4-methyl-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-

4-ylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-4-methylquinolin-2- yl} -phenylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-phenylquinolin-4- yl}-methylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-pyridin-2- ylquinolin-4-yl } -methylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-thiophen-2- ylquinolin-4-yl } -methylamine;

7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7//-pyrτolo[2,3-rf]pyrimidin-5-yl]-λλ-methyl-λ^- phenylquinoline-2,4-diamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-phenoxyquinolin-

4-yl } -methylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-pyridm-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine,

7-(3-Dirnethylaminornethylcyclobutyl)-5-(2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyππiidin-4- ylamine,

7-(3-Dirnethylaminornethylcyclobutyl)-5-(2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine,

{7-[4-Amino-7-(3-dimethy1aminomethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-quinolin-2-yl}- phenylamine;

5-(6-Chloro-2-phenylquinolin-7-yl)-7-(3-dimethylaminomethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-

4-ylamine,

5-(6-Chloro-2-pyridin-2-ylquinohn-7-yl)-7-(3-dimethylaminomethylcyclobutyl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine,

5-(6-Chloro-2-thiophen-2-ylquιnohn-7-yl)-7-(3-dimethylaminomethylcyclobutyl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

{7-[4-Amino-7-(3-dimethylaminomethylcyclobutyl)-7H-pyrτolo[2,3-d]pyrimidin-5-yl]-6-chloroquinolin-

2-yl } -phenylamine,

5-(6-Chloro-2-phenoxyquinohn-7-yl)-7-(3-dimethylaminomethylcyclobutyl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine,

7-(3-Dimethylaminomethylcyclobutyl)-5-(8-fluoro-2-phenylquinohn-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-

4-ylamine,

7-(3-Dimethylaminomethylcyclobutyl)-5-(8-fluoro-2-thiophen-2-ylqumolin-7-yl)-7H-pyrrolo[2,3- d]pyπmidin-4-ylamine;

7-(3-Dimethylammomethylcyclobutyl)-5-(8-fluoro-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3- d]pynmidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(4-methyl-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-

4-ylamine,

7-(3-Dimethylaminomethylcyclobutyl)-5-(4-methyl-2-pyπdin-2-ylquinohπ-7-yl)-7H-pyττolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(4-methyl-2-phenoxyquinohn-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

4-[4-Amino-5-(2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide,

4-[4-Amino-5-(2-pyndin-2-ylquinohn-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxyhc acid amide,

4-[4-Amino-5-(2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(2-phenylquinolin-7-yl)-pyrrolo[2,3-d]ρyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(2-pyridin-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(6-chloro-2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(6-chloro-2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

7-(4-Aminomethylcyclohexyl)-5-(2-thiophen-2-ylquinolin-7-yl)-7H-pyrτolo[2,3-d]pyrimidin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(2-pyridin-2-ylquinolin-7-yl)-7H-pyrτolo[2,3-d]pyrimidin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-chloro-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-chloro-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyriinidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(4-methyl-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(4-methyl-2-ρhenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine; l -(4-Aminomethylcyclohexyl)-3-(2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l^-AminomethylcyclohexyOO^-pyridin-2-yl-quinolin^-y^-lH-pyrazolotS^-dlpyrimidin^-ylamine;

1 -(4-Aminomethylcyclohexyl)-3-(2-phenoxyquinolin-7-yl)- 1 H-pyrazolo [3 ,4-d]pyrimidin-4-ylamine; l -(4-Aminomethylcyclohexyl)-3-(2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine; l-(4-Aminomethylcyclohexyl)-3-(6-chloro-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-

4-ylamine; l -(4-Aminomethylcyclohexyl)-3-(6-chloro-2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(4-methyl-2-thiophen-2-ylquinoliπ-7-y])-lH-pyrazolo[3,4-d]pyrimidin-

4-ylamine; l^-AminomethylcyclohexyOO^-methyl^-pyridin-2-ylquinolin^-yO-lH-pyrazoloP^-dlpyrimidin^- ylamine; l-(4-Aminomethylcyclohexyl)-3-(4-methyl-2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(4-methyl-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(8-fluoro-2-thiophen-2-yl-quinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-

4-ylamine; l-(4-Aminomethylcyclohexyl)-3-(8-fluoro-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(8-fluoro-2-phenoxyquinolm-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine;

l-(4-Aminomethylcyclohexyl)-3-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine;

4-[4-Amino-3-(2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-y]]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(6-chloro-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(6-chloro-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(8-fluoro-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(8-fluoro-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(4-methyl-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3 -(4-methyl-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3 ,4-d]pyrimidin- 1 -yl] - cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(4-methyl-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(2-thiophen-2-ylqumolin-7-yl)-pyrazolo[3,4-d]pynmidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyτimidin-l-yl]-cyclohexanecarboxyhc acid methylamide;

4-[4-Amιno-3-(6-chloro-2-phenylquinohn-7-yl)-pyrazolo[3,4-d]pyπmidin-l-yl]-cyclohexanecarboxyhc acid methylamide;

4-[4-Ammo-3-(6-chloro-2-pyndin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pynmidm-l-yl]- cyclohexanecarboxyhc acid methylamide;

4-[4-Amino-3-(6-chloro-2-thiophen-2-ylqumolin-7-yl)-pyrazolo[3,4-d]pyπmidin-l-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(6-chloro-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyπmidin-l -yl]-cyclohexanecarboxyhc acid methylamide;

4-[4-Amino-3-(8-fluoro-2-phenylquinolin-7-yl)-pyτazolo[3,4-d]pyτimidin-l -yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(6-chloro-2-thiophen-2-ylquinohn-7-yl)-pyrazolo[3,4-d]pyπmidin-l-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(8-fluoro-2-pyndin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyπmidin-l-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Ammo-3-(8-fluoro-2-phenoxyquinolm-7-yl)-pyrazolo[3,4-d]pyπmidin-l-yl]-cyclohexanecarboxylic acid methylamide,

4-[4-Amino-3-(4-methyl-2-phenylquinohn-7-yl)-pyrazolo[3,4-d]pyπmidin-l-yl]-cyclohexanecarboxyhc acid methylamide;

4-[4-Ammo-3-(4-methyl-2-miophen-2-ylquinohn-7-yl)-pyrazolo[3,4-d]pyπmidin-l-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(4-methyl-2-pyridin-2-ylquinohn-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxyhc acid methylamide;

4-[4-Amino-3-(4-methyl-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxyhc acid methylamide; l-Cyclobutyl-3-(2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyπmidin-4-ylamine; l-Cyclobutyl-3-{2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine,

1 -Cyclobutyl-3 -(2-phenoxyquinohn-7-yl)- 1 H-pyrazolo[3 ,4-d]pyrimidin-4-ylamine; l-Cyclobutyl-S^-pyπdin-2-ylquinohn^-yO-lH-pyrazolofS^-dJpyrimidin^-ylamine,

S^ό-Chloro^-phenylquinohn^-yO-l-cyclobutyl-lH-pyrazoloP^-dJpynmidm^-ylamine;

3-(6-Chloro-2-pyridin-2-ylquinohn-7-yl)-l-cyclobutyl-lH-pyrazolo[3,4-d]pyπmidm-4-ylamine;

S^β-Chloro^-thiophen-2-ylquinohn^-y^-l-cyclobutyl-lH-pyrazolofS^-dJpyπmidiii^-ylamine,

3-(6-Chloro-2-phenoxyquinolin-7-yl)-l-cyclobutyl-lH-pyrazolo[3,4-d]pyπmidin-4-ylamine; l-Cyclobutyl-3-(4-methyl-2-thiophen-2-ylquinohn-7-yl)-lH-pyrazolo[3,4-d]pyτimidin-4-ylamine _J l-Cyclobutyl-3-(4-methyl-2-pyridin-2-ylquinohn-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine;

l-Cyclobutyl-S^-methyl^-phenylquinolin-7-yO-lH-pyrazoiofS^-djpyrimidin^-ylamine; l-Cyclobutyl-3-(4-methyl-2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine; 3-[4-Amino-S^-phenylquinolin-y-y^-pyrazolofS^-dJpyrimidin-l-y^-cyclobutanol;

3-[4-Amino-3 -(2-pyridin-2-ylquinolin-7 -yl)-pyrazolo [3 ,4-d]pyrimidin- 1 -yl] -cyclobutanol ;

3-[4-Amino-3-(2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3 ,4-d]pyrimidin- 1 -yl]-cyclobutanol;

3-[4-Amino-3-(2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyra2olo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(6-chloro-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(6-chloro-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(4-methyl-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l -yl]-cyclobutanol;

3-[4-Amino-3-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(4-methyl-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l -yl]-cyclobutanol; l-(3-Azetidin-l-ylmethylcyclobutyl)-3-(2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine;

1 -(3 - Azetidin-1 -ylmethylcyclobutyl)-3 -(2-phenylquinolin-7-yl)- 1 H-pyrazolo [3 ,4-d]pyrimidin-4-ylamine; l-(3-Azetidin-l-ylmethylcyclobutyl)-3-(2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-CS-Azetidin-l-ylmethylcyclobuty^-S^-phenoxyquinolin^-y^-lH-pyrazolotS^-dJpyrimidin^- ylamine;

1 -(3-Azetidin- 1 -ylmethylcyclobutyl)-3 -(6-chloro-2-thiophen-2-ylquinolin-7-yl)-l H-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Azetidin-l-ylmethylcyclobutyl)-3-(6-chloro-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(3-Azetidin-l-ylmethylcyclobutyl)-3-(6-chloro-2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-

4-ylamine; l-(3-Azetidin-l-ylmethylcyclobutyl)-3-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-CS-Azetidin-l-ylmethylcyclobutyO-S^-methyl^-pyridin-2-ylquinolin^-yO-lH-pyrazolo^^- d]pyriτnidin-4-ylamine;

1 -(3 -Azetidin- 1 -ylmethylcyclobutyl)-3-(4-methyl-2-phenylquinolin-7-yl)- 1 H-pyrazolo[3 ,4-d]pyrimidin-

4-ylamine; l-CS-Azetidin-l-ylmethylcyclobutyO^^-methyl^-thiophen-2-ylquinolin^-yO-lH-pyrazolotS^- d]pyrimidin-4-ylamine; l-(3-Azetidin-l-ylmethylcycIobutyl)-3-(4-methyl-2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine;

^(S-DimethylaminomethylcyclobutyO-S-Cl-phenylquinolin-7-y^-lH-pyrazolo^^-dlpyrimidin^- ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(2φyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyriτnidin-4- ylamine;

1 -(3 -Dimethylaminomethylcyclobutyl)-3 -(2-phenoxyquinolin-7-yl)- 1 H-pyrazolo[3 ,4-d]pyrimidin-4- ylamine;

3 -(6-Chloro-2-phenylquinolin-7-yl)- 1 -(3-dimethylaminomethylcyclobutyl)- 1 H-pyrazolo [3 ,4- d] pyrimidin-4-ylamine ;

3-(6-Chloro-2-thiophen-2-ylquinolin-7-yl)-l-(3-dimethylaminomethylcyclobutyl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine;

3-(6-Chloro-2-phenoxyquinolin-7-yl)-l-(3-dimethylaminomethylcyclobutyl)-lH-pyrazolo[3,4- d] pyrimidin-4-ylamine ;

3-(6-Chloro-2-pyridin-2-ylquinolin-7-yl)-l-(3-dimethylaminomethylcyclobutyl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(4-methyl-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(4-methyl-2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(8-fluoro-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-

4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l^S-DimethylaminomethylcyclobutyO-S^S-fluoro^-thiophen-2-ylquinolin^-y^-lH-pyrazolotS^- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(8-fluoro-2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4- d] pyrimidin-4-ylamine;

3-Cyclobutyl-l-(3-phenylquinoxalin-6-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

3-[8-Amino-l-(3-phenylquinoxalin-6-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(3-phenylquinoxalin-6-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

4-[8-Amino-l-(3-phenylquinoxalin-6-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l -(3-ρhenylquinoxalin-6-yl)-imidazo[ 1 ,5-a]ρyrazin-3-yl]-cyclohexanecarboxylic acid methylamide;

4-[8-Amino-l-(2-phenylquinazolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(2-phenylquinazolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxyhc acid methylamide,

3-Cyclobutyl- 1 -(2-phenylquinazolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-8-ylamine;

3-[8-Ammo-l-(2^henylquinazolm-7-yl)-imidazo[l,5-a]pyrazm-3-yl]<;yclobutanol;

3-(3-Azetidin-l -ylmethylcyclobutyl)- 1 -(2-phenylquinazohn-7-yl)-imidazo[l ,5-a]pyrazin-8-ylamme,

3-[3-(2-Methoxyethoxy)-cyclobutyl]-l-(2-phenylquinolin-7-yl)-iinidazo[l,5-a]pyrazin-8-ylamine, l-(6-Chloro-2-phenylquinolin-7-yl)-3-[3-(2-methoxyethoxy)-cyclobutyl]-imidazo[l,5-a]pyrazin-8- ylamine,

3-[3-(2-Methoxyethoxy)-cyclobutyl]-l-(4-methyl-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine,

3-(l-Methyl-l,2,3,6-tetrahydropyndin-4-yl)-l-(2-phenylquinolin-7-yl)-imidazo[l ,5-a]pyrazin-8-ylamme; l-{4-[8-Amino-l-(2-phenylqumolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-3,6-dihydro-2H-pyridin-l-yl}- ethanone,

3-Bicyclo[3.1.0]hex-6-yl-l-(2-phenylquinolm-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine; o-fS-Amino-l^-phenylquinohn^-y^-imidazof l.S^pyrazin-S-yll-bicyclop.l.Olhexan^-ol;

7-Cyclobutyl-5-(2-phenylquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-4-ylamine,

7-Cyclobutyl-5-(2-thiophen-2-ylquinolin-7-yl)-imidazo[5,l-f][l,2,4]tπazin-4-ylamine;

7-Cyclobutyl-5-(2-phenoxyquinolin-7-yl)-imidazo[5,l-f][l,2,4]tπazm-4-ylamine;

7-Cyclobutyl-5-(2-pyridin-2-ylquinohn-7-yl)-imidazo[5,l-f][l,2,4]tnazin-4-ylamine,

3-[4-Ammo-5-(2-phenylquinolm-7-yl)-imidazo[5,l -f] [1 ,2,4]tnazin-7-yl]-cyclobutanol; 3-[4-Amino-5-(2-thiophen-2-ylquinohn^-y^-imidazofS.l-fltl^^Jtnazin^-y^-cyclobutanol,

3-[4-Amino-5-(2-phenoxyquinolin-7-yl)-imidazo[5 , 1 -f] [ 1 ,2,4]tπazin-7-yl]-cyclobutanol;

3-[4-Amino-5-(2-pyπdm-2-ylquinolin-7-yl)-imidazo[5,l-f][l,2,4]tπazm-7-yl]-cyclobutanol;

7-(3-Azetidin-l -ylmethylcyclobutyl)-5-(2-phenylquinolin-7-yl)-imidazo[5,l-f][l,2,4]tπazin-4-ylamine,

7-(3-Azetidin-l ylamme,

7-(3 -Azetidin- 1 -ylmethylcyclobutyl)-5 -(2-phenoxyquinohn-7-yl)-imidazo[5 , 1 -f] [ 1 ,2 ,4] triazin-4-ylamine,

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-pyridin-2-ylquinolin-7-yl)-imidazo[5, l-f][l,2,4]tτiazin-4- ylamine,

7-(3-Dimethylammomethylcyclobutyl)-5-(2-pyridin-2-ylquinohn-7-yl)-imidazo[5,l-f][l,2,4]tπazin-4- ylamine,

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-thiophen-2-ylquinolin-7-yl)-imidazo[5, 1 -f] [ 1 ,2,4]tπazin-4- ylamine;

7-(3-Dimethylaminotnethylcyclobutyl)-5-(2-phenylquinohn-7-yl)-imidazo[5,l-f][l,2,4]tnazin-4-ylamine;

7-(3-Dimethylaτninomethylcyclobutyl)-5-(2-phenoxyquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-4- ylamine;

4-[4-Amino-5-(2-phenylquinolin-7-yl)-imidazo[5, 1 -f][l ,2,4]triazin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(2-thiophen-2-ylquinolin-7-yl)-imidazo[5, 1 -f][ 1 ,2,4]triazin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(2-phenoxyquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Aτnino-5-(2-phenylquinolin-7-yl)-imidazo[5,l-f|[l,2,4]triazin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(2-thiophen-2-ylquinolin-7-yl)-imidazo[5,l-f][l ₁ 2,4]triazin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(2-phenoxyquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-7-yl]-cyclohexanecarboxylic acid methylamide;

7-(4-Aminomethylcyclohexyl)-5-(2-phenylquinolin-7-yl)-imidazo[5,l-f][l ,2,4]triazin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(2-thiophen-2-ylquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(2-pheπoxyquinolin-7-yl)-imidazo[5,l -f][l,2,4]triazin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-chloro-2-phenylquinolin-7-yl)-imidazo[5,l-f|[l,2,4]triazin-4- ylamine;

4-[4-Amino-5-(6-chloro-2-phenylquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(6-chloro-2-pheny1quinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-7-yl]-cyclohexanecarboxylic acid methylamide;

5-(6-Chloro-2-phenylquinolin-7-yl)-7-cyclobutylirnidazo[5, 1 -fj[ 1 ,2,4]triazin-4-ylamine; 3-[4-Amino-S-ζό-chloro^-phenylquinolin^-y^-imidazofSjl-flfl^^triazin^-ylJ-cyclobutanol;

7-(3-Azetidin-l -ylmethylcyclobutyl)-5-(6-chloro-2-phenylquinolin-7-yl)-imidazo[5, 1 -f][ 1 ,2,4]triazin-4- ylamine;

7-(3-Azetidin-l-ylmethylcyc1obutyl)-5-(2-phenylquinolin-7-yl)-5H-pyrτolo[3,2-d]pyrimidin-4-ylamine; 3-[4-Amino-5-(2-phenylquinolin^-y^-SH-pyrrolotB^-dJpyrimidin^-y^-cyclobutanol;

7-Cyclobutyl-5-(2-phenylquinolin-7-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-ylamine;

7-Phenyl-5-(2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamme;

3-Isopropyl-l-(2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

3-tert-Butyl-1 -(2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

5-[8-Amino-l-(2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-pyrrolidin-3-ol;

S-Cyclobutyl-l^-phenylquinolin^-ylJ^H-imidazotl .S-αJpyrazin-δ-ylamine; trans- 4-[8-Amino-l -(2-phenylquinolin-7-yl)-imidazo[l ,5-α]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

/rαnj-4-[8-Amino-l -(2-phenylquinolin-7-yl)-imidazo[l,5-α]pyrazin-3-yl]-cyclohexanecarboxylic acid methyl ester;

/rαrts-4-[8- Amino- 1 -(2-phenylquinolin-7-yl)-imidazo[ 1 ,5-α]pyrazin-3-yl]-cyclohexanecarboxylic acid;

/ra/is-4-[8-Amino-l-(2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylamide;

/rα/ιs-{4-[8-Amino-l(2-phenylquinolin-7-yl)-imidazo[l,5-α]pyrazin-3-yl]-cyclohexyl}-methanol; rrαAZ5-2-{4-[8-Amino-l-(2-phenylquinolin-7-yl)-imidazo[l,5-α]pyrazin-3-yl]-cyclohexylmethyl}- isoindole- 1 ,3 -dione;

3-(4-Aminomethyl-cyclohexyl)-l-(2-phenyl-quinolin-7-yl)-imidazo[l,5-a] pyrazin-8-ylamine; frα/w-3-[4-AminomethylcyclohexyO-l-^φhenylquinolin^-yO-imidazoP.S-α] pyrazin-8-ylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(2-phenylquinolin-7-yl)-imidazo[l,5-α]pyrazin-8-ylamine; c«-3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(2-phenylquinolin-7-yl)-imidazo[l,5-α]pyrazin-8-ylamine; and {3-[8-Amino-l-(2-phenylquinolin-7-yl)-imidazo[l,5-α]pyrazin-3-yl]-cyclobutyl}-methanol.

4. The pharmaceutical composition of claim 1 wherein the IGFR inhibitor is selected from the group consisting of:

5. The pharmaceutical composition of claim 1 wherein the IGFR inhibitor is selected from the group consisting of:

6. The pharmaceutical composition of claim 1, wherein the anti-cancer agent is an EGFR kinase inhibitor, MEK inhibitor, VEGFR inhibitor, anti-VEGFR2 antibody, KDR antibody, AKT inhibitors, PDK-I inhibitors, PI3K inhibitors, c-kit/Kdr tyrosine kinase inhibitor, Bcr-Abl tyrosine kinase inhibitor, VEGFR2 inhibitor, PDGFR-beta inhibitor, KIT inhibitor, Flt3 tyrosine kinase inhibitor, PDGF receptor family inhibitor, Flt3 tyrosine kinase inhibitor, RET tyrosine kinase receptor inhibitor, VEGF-3 receptor antagonist, Raf protein kinase inhibitor, angiogenesis inhibitor, Erb2 inhibitor, mTOR inhibitor, IGF-IR antibody, NFkB inhibitor, proteosome inhibitor, chemotherapy agent, or glucose reduction agent.

7. The pharmaceutical composition of claim 1, wherein the anti-cancer agent is ARRY-142886, PD-184352, PD-98059, ZD-6474, IMC-1121b, CDP-791, imatinib, sunitinib malate, sorafenib, PTK-787, lapatinib, sirolimus, temsirolimus, everolimus, CP-751871, RAV-12, IMC-A12, 19D12, PS-1 145, or orbortezomib.

8. The pharmaceutical composition of claim 6, wherein the anti -cancer agent is an EGFR kinase inhibitor.

9. The pharmaceutical composition of claim 8, wherein the EGFR kinase inhibitor is erlotinib, cetuximab, gefitinib, or a salt thereof.

10. The pharmaceutical composition of claim 9, wherein the EGFR kinase inhibitor is erlotinib or a salt thereof.

11 The pharmaceutical composition of claim 2, wherein the EGFR kinase inhibitor is erlotinib or a salt thereof.

12. The pharmaceutical composition of claim 10, further comprising one or more other anticancer agents

13 The composition of claim 12 wherein said other anti -cancer agent is an alkylating drug, antimetabolite, microtubule inhibitor, podophyllotoxin, antibiotic, nitrosourea, hormone therapy, kinase inhibitor, activator of tumor cell apoptosis, antiangiogenic agent, mitotic inhibitor, intercalating antibiotic, growth factor inhibitor, cell cycle inhibitor, an enzyme, a topoisomerase inhibitor, biological response modifier, an anti-hormonal agent, or an anti-androgen.

14. The pharmaceutical composition of claim 6, wherein the anti-cancer agent is a glucose reduction agent

15. The pharmaceutical composition of claim 14, wherein the glucose reduction agent is a PP ARa agonist, PPARγ agaonist, PPAR dual agonist, biguamde, ghtazone, or metformin.

16 The pharmaceutical composition of claim 15, further comprising one or more other anticancer agents

17. The composition of claim 16 wherein said other anti-cancer agent is an alkylating drug, antimetabolite, microtubule inhibitor, podophyllotoxin, antibiotic, nitrosourea, hormone therapy, kinase inhibitor, activator of tumor cell apoptosis, antiangiogenic agent, mitotic inhibitor, intercalating antibiotic, growth factor inhibitor, cell cycle inhibitor, an enzyme, a topoisomerase inhibitor, biological response modifier, an anti-hormonal agent, or an anti-androgen.

18 A method for treating cancer in a patient, comprising administering to said patient simultaneously or sequentially (i) a therapeutically or sub-therapeautically effective amount of an anticancer agent, or a pharmaceutically salt thereof, and (π) a therapeutically or sub-therapeautically effective amount an IGFR inhibitor represented by Formula I

I or a pharmaceutically acceptable salt thereof, wherein: Xι and X ₂ are each independently N or — C-(E') _aa , X ₅ is N, -C-(E') _aa , or -N-(E') _aa ; X ₃ , X ₄ , X ₆ , and X ₇ are each independently N or C; wherein at least one of X ₃ , X ₄ , X ₅ , X ₆ , and X ₇ is independently N or -N-(E ¹ ),,,,, Q ¹ is

Xn, X ₁₂ , Xi3, Xi4, Xi5, and X, ₆ are each independently N, -C-(E ¹¹ V, Or -N ⁺ -O ^' ; wherein at least one of Xn, Xi ₂ , Xn, X _M , Xis, and X ₎₆ is N or -N ⁺ -O ^" ;

R ¹ is absent, Co-ι _O alkyl, cycloC _3- , _o alkyl, bicycloC ₅ .i ₀ alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, heterobicycloCs.ioalkyl, spiroalkyl, or heterospiroalkyl, any of which is optionally substituted by one or more independent G ¹ ' substituents;

E ¹ , E", G ¹ , and G ⁴¹ are each independently halo, -CF ₃ , -OCF ₃ , -OR ² , -NR ² R ³ (R ^2a )j,, -C(=0)R ² , -CO ₂ R ² , -CONR ² R ³ , -NO ₂ , -CN, -S(O) _j ,R ² , -SO ₂ NR ² R ³ , -NR ² C(=O)R ³ , -NR ² C(O)OR ³ , -NR ² C(O)NR ³ R ² ", -NR ² S(O)j,R ³ , -C(=S)OR ² , -C(O)SR ² , -NR ² C(=NR ³ )NR ^2a R ^3a , -NR ² C(=NR ³ )OR ^2a , -NR ² C(=NR ³ )SR ^2a , -OC(=O)OR ² , -OC(=O)NR ² R ³ , -OC(O)SR ² , -SC(=O)OR ² , -SC(=O)NR ² R ³ , C _0-1O aIlCyI, C ₂ -ιoalkenyl, C ₂ -ioalkynyl, C,.,oalkoxyC _1-10 alkyl, CnoalkoxyC^oalkenyl, C ₁ . , ₀ alkoxyC _2- ,oalkynyl, Ci.ioalkylthioCi.ioalkyl, Ci _-)0 alkylthioC _2-1 oalkenyl, C|.ioalkylthioC ₂ .ιoalkynyl, cycloC ₃ . _g alkyl, cycloC _3-8 alkenyl, cycloC _3-8 alkenylC|-i _O alkyl, cycloC _3-8 alkylC ₂ - i _O alkenyl, cycloC _3-8 alkenylC _2- ioalkenyl, cycloC ₃ . ₈ alkylC _2- i ₀ alkynyl, cycloC ₃ . ₈ alkenylC ₂ .κ>alkynyl, heterocyclyl-Co-ioalkyl, heterocyclyl— C ₂ .ioalkenyl, or heterocyclyl-C _2- | ₀ alkynyl, any of which is optionally substituted with one or more independent halo, oxo, -CF ₃ , -OCF ₃ , —OR ²²² , -NR ²²² R ³³³ (R ^222a ) _jla , -C(O)R ²²² , -CO ₂ R ²²² , -C(=O)NR ²²² R ³³³ , -NO ₂ , -CN, -S(=O) _jla R ²²² , -SO ₂ NR ²²² R ³³³ , -NR ²²² C(=O)R ³³³ , -NR ²²² C(O)OR ³³³ , -NR ²²² C(=O)NR ³³³ R ^222a , -NR ²²² S(O) _jIa R ³³³ , -C(=S)OR ²²² , -C(=O)SR ²²² , -NR ²²² C(=NR ³³³ )NR ^222a R ^333a , -NR ²²² C(=NR ³³³ )OR ^222a , -NR ²²² C(=NR ³³³ )SR ^222a , -OC(=O)OR ²²² , -OC(=O)NR ²²² R ³³³ , -OC(O)SR ²²² , -SC(O)OR ²²² , or -SC(O)NR ²²² R ³³³ substituents; or E ¹ , E", or G ¹ optionally is -(W ¹ ) _n -(Y') _m -R ⁴ ; or E ¹ , E ^{1 1} , G ¹ , or G ⁴¹ optionally independently is aryl-Co-ioalkyl, aryl— C ₂ _ioalkenyl, aryl-C _{2- l} oalkynyl, hetaryl-Co-ioalkyl, hetaryl— C ₂ .ioalkenyl, or hetaryl-C ₂ .ιoalkynyl, any of which is optionally substituted with one or more independent halo, -CF ₃ , -OCF ₃ , -OR ²²² , -NR ²²² R ³³³ (R ^222a ) _j2a , -C(O)R ²²² , -CO ₂ R ²²² , -C(O)NR ²²² R ³³³ , -NO ₂ , -CN, -S(O) _j2a R ²²² , -SO ₂ NR ²²² R ³³³ , -NR ²²² C(O)R ³³³ , -NR ²²² C(O)OR ³³³ , -NR ²²² C(O)NR ³³³ R ²²² ", -NR ²²² S(O) _j2a R ³³³ , -C(=S)OR ²²² , -C(O)SR ²²² , -NR ²²² C(=NR ³³³ )NR ^222a R ^333a , -NR ²²² C(=NR ³³³ )OR ^222a , -NR ²²² C(=NR ³³³ )SR ^222a , -OC(=O)OR ²²² , -OC(=O)NR ²²² R ³³³ , -OC(=O)SR ²²² , -SC(O)OR ²²² , or -SC(O)NR ²²² R ³³³ substituents;

G" is halo, oxo, -CF ₃ , -OCF ₃ , -OR ²¹ , -NR ²¹ R ³¹ (R ^2al ) _j4) -C(O)R ²¹ , -CO ₂ R ²¹ , -C(O)NR ²¹ R ³¹ , -NO ₂ , -CN, -S(O) _j4 R ²¹ , -SO ₂ NR ²¹ R ³¹ , NR ^2I (CO)R ³¹ , NR ²¹ C(O)OR ³¹ , NR ²¹ C(O)NR ³¹ R ² " ¹ , NR ²¹ S(O) _J4 R ³¹ , -C(=S)OR ²¹ , -C(O)SR ²¹ , -NR ²¹ C(=NR ³¹ )NR ^2al R ^3al , -NR ²¹ C(=NR ^3l )OR ^2al , -NR ²¹ C(=NR ^3l )SR ^2al , -OC(=O)OR ²¹ , -OC(=O)NR ²¹ R ³¹ , -OC(O)SR ²¹ , -SC(O)OR ²¹ ,

-SC(=O)NR ^2I R ³¹ , -P(O)OR ²¹ OR ³¹ , C _MO alkylidene, Co. ₁₀ alkyl, C ₂ .ioalkenyl, C _2- ioalkynyl ₎ C,. ₁₀ alkoxyC,. _l oalkyl, C|. ₁₀ alkoxyC ₂ .ie>alkenyl, C|.ι ₀ alkoxyC _2- ioalkynyl, Ci.ioalkylthioCi.ioalkyl, Ci.i ₀ alkylthioC ₂ . , _o alkenyl, d.ioalkylthioC _∑ .ioalkynyl, cycloC ₃ . ₈ alkyl, cycloC ₃ .galkenyl, cycloC ₃ . ₈ alkenylC _MO alkyl, cycloC _3-8 alkylC ₂ .,oalkenyl, cycloC _3-8 alkenylC ₂ .,oalkenyl, cycloC ₃ . ₈ alkylC ₂ _ioalkynyl, cycloC _3-8 alkenylC _2- ioalkynyl, heterocyclyl-C _d oalkyl, heterocyclyl-C _2- ioalkenyl, or heterocyclyl-C ₂ . _l oalkynyl, any of which is optionally substituted with one or more independent halo, oxo, -CF ₃ , -OCF ₃ , -OR ²²²¹ , -NR ²²²¹ R ³³³¹ (R ²²²³ V, -C(O)R ²²²¹ , -CO ₂ R ²²² ', -C(=O)NR ²²²¹ R ³³³¹ , -NO ₂ , -CN, -S(O) _j4a R ²²²¹ , -SO ₂ NR ²²²¹ R ³³³¹ , -NR ²²²¹ C(=O)R ³³³¹ , -NR ²²²¹ C(MO)OR ³³³¹ , -NR ²²²¹ C(=O)NR ³³³¹ R ^222al , -NR ²²²¹ S(O) _j4a R ³³³¹ , -C(=S)OR ²²²¹ , -C(=O)SR ²²²¹ , -NR ²²²¹ C(=NR ³³³¹ )NR ^{222a l} R ^333al , -NR ²²²¹ C(=NR ^{333 l} )OR ^222al , -NR ^{222 l} C(=NR ³³³¹ )SR ^222al , -OC(=O)OR ²²²¹ , -OC(=O)NR ^222I R ³³³¹ , -OC(=O)SR ²²²¹ , -SC(=0)OR ²²²¹ , -P(O)OR ²²²¹ OR ³³³¹ , or -SC(=O)NR ²²²¹ R ³³³¹ substituents; or G" is aryl-Cc _M oalkyl, aryl-C ₂ .| ₀ alkenyl, aryl-C ₂ -ioalkynyl, hetaryl-Co.i ₀ alkyl, hetaryl-C ₂ . _l oalkenyl, or hetaryl— C _2- ioalkynyl, any of which is optionally substituted with one or more independent halo, -CF ₃ , -OCF ₃ , -OR ²²²¹ , -NR ^222I R ³³³¹ (R ^222al ) _j5a , -C(O)R ²²²¹ , -CO ₂ R ²²²¹ , -C(=O)NR ^222l R ³³³ \ -NO ₂ , -CN, -S(O) _j5a R ²²²¹ , -SO ₂ NR ²²²¹ R ³³³¹ , -NR ^222I C(=O)R ³³³¹ , -NR ²²²¹ C(=O)OR ³³³¹ , -NR ²²²¹ C(=O)NR ^{333 l} R ^222al , -NR ²²²¹ S(O)J ₅₈ R ³³³¹ , -C(=S)OR ²²²¹ , -C(=O)SR ²²²¹ , -NR ²²²¹ C(=NR ³³³¹ )NR ^222al R ^333aI , -NR ²²²¹ C(=NR ^333l )OR ^222al , -NR ²²²¹ C(=NR ³³³¹ )SR ^222al , -OC(=O)OR ²²²¹ , -OC(=O)NR ^222I R ³³³¹ , -OC(=O)SR ²²²¹ , -SC(=O)OR ²²²¹ , -P(O)OR ²²²¹ OR ³³³¹ , or -SC(=O)NR ^{222 I} R ³³³¹ substituents; or G' ' is C, taken together with the carbon to which it is attached forms a C=C double bond which is substituted with R ⁵ and G ^{1 1 1} ;

R ² , R ^2a , R ³ , R ^3a , R ²²² , R ^222a , R ³³³ , R ^333a , R ²¹ , R ^2aI , R ³¹ , R ^3al , R ²²²¹ , R ^222al , R ³³³¹ , and R ^333aI are each independently Co-ioalkyl, C _2- ioalkenyl, C ₂ -ioalkynyl, Ci.ioalkoxyCi.ioalkyl, Ci. ₁₀ alkoxyC ₂ .ioalkenyl, Q. ioalkoxyC ₂ .| ₀ alkynyl, Ci.ioalkylthioCi.ioalkyl, C _M oalkylthioC _2- | ₀ alkynyl, cycloC _3-8 alkyl, cycloC _3-8 alkenyl, cycloC _3-8 alkylCi.ioalkyl, cycloC _3-8 alkenylC _MO alkyl, cycloC ₃ . ₈ alkylC _2- i _O alkeny], cycloC ₃ . _g alkenylC ₂ .ιoalkenyl, cycloC _3-8 alkylC ₂ .ioalkynyl, cycloC ₃ . ₈ alkenylC _2- ioalkynyl, heterocyclyl-Co-ioalkyl, heterocyclyl-C ₂ .ioalkynyl, aryl-Co-ioalkyl, aryl— C _{2- 10} alkenyl, aryl-C ₂ _ioalkynyl, hetaryl— Co-ioalkyl, hetaryl-C ₂ .| _O alkenyl, or hetaryl-C ₂ .i _O alkynyl, any of which is optionally substituted by one or more independent G ^{11 1} substituents; or in the case of -NR ² RW)J ₁ or -NR ²²² R ³³³ (R ^222a ) _jla or -NR ²²² R ³³³ (R ^222a ) _j2a or -NR ^2I R ^{3 l} (R ^2al ) _j4 or -NR ²²²¹ R ³³³ W ²²³ V Or -NR ²²²¹ R ³³³¹ (R ^222al ) _j5a , then R ² and R ³ , or R ²²² and R ³³³ , or R ²²²¹ and R ³³³¹ , respectfully, are optionally taken together with the nitrogen atom to which they are attached to form a 3- 10 membered saturated or unsaturated ring, wherein said ring is optionally substituted by one or more independent G ^{u u} substituents and wherein said ring optionally includes one or more heteroatoms other than the nitrogen to which R ² and R ³ , or R ²²² and R ³³³ , or R ²²²¹ and R ³³³¹ are attached;

W ¹ and Y ¹ are each independently -O-, -NR ⁷ - ^' , -S(O) _j7 -, -CR ⁵ R ⁶ -, -N(C(O)OR ⁷ )-, -N(C(O)R ⁷ )-, -N(SO ₂ R ⁷ )-, -CH ₂ O-, -CH ₂ S-, -CH ₂ N(R ⁷ )-, -CH(NR ⁷ )-, -CH ₂ N(C(O)R ⁷ )-, -CH ₂ N(C(O)OR ⁷ )-, -CH ₂ N(SO ₂ R ⁷ )-, -CH(NHR ⁷ )-, -CH(NHC(O)R ⁷ )-, -CH(NHSO ₂ R ⁷ )-, -CH(NHC(O)OR ⁷ )-, -CH(OC(O)R ⁷ )-, -CH(OC(O)NHR ⁷ )-, -CH=CH-, -C≡C-, -C(=NOR ⁷ )-, -C(O)-, -CH(OR ⁷ )-, -C(O)N(R ⁷ )-, -N(R ⁷ )C(O)-, -N(R ⁷ )S(O)-, -N(R ⁷ )S(O) ₂ - -OC(O)N(R ⁷ )-, -N(R ⁷ )C(O)N(R ⁸ h -NR ⁷ C(O)O-, -S(O)N(R ⁷ )-, -S(O) ₂ N(R ⁷ )-, -N(C(O)R ⁷ )S(O)-, -N(C(O)R ⁷ )S(O) ₂ -, -N(R ⁷ )S(O)N(R ⁸ )-, -N(R ⁷ )S(O) ₂ N(R ⁸ )-, -C(O)N(R ⁷ )C(O)-, -S(O)N(R ⁷ )C(O)-, -S(O) ₂ N(R ⁷ )C(O)- ₎ -OS(O)N(R ⁷ )-, -OS(O) ₂ N(R ⁷ )-, -N(R ⁷ )S(O)O-, -N(R ⁷ ) S(O) ₂ O-, -N(R ⁷ )S(O)C(O)-, -N(R ⁷ )S(O) ₂ C(O)-, -SON(C(O)R ⁷ )-, -SO ₂ N(C(O)R ⁷ )-, -N(R ⁷ )SON(R ⁸ )-, -N(R ⁷ )SO ₂ N(R ⁸ )- _> -C(O)O-, -N(R ⁷ )P(OR ⁸ )O-, -N(R ⁷ )P(OR ⁸ )-, -N(R ⁷ JP (O)(OR ⁸ )O-, -N(R ⁷ )P(O)(OR ⁸ K -N(C(O)R ⁷ )P(OR ⁸ )O-, -N(C(O)R ⁷ )P(OR ⁸ )-, -N(C(O)R ⁷ )P(O)(OR ⁸ )O-, -N(C(O)R ⁷ )P(OR ⁸ )-, -CH(R ⁷ )S(O)-, -CH(R ⁷ )S(O) ₂ -, -CH(R ⁷ )N(C(O)OR ⁸ )-, -CH(R ⁷ )N(C(O)R ⁸ )-, -CH(R ⁷ )N(SO ₂ R ⁸ )-, -CH(R ⁷ )O-, -CH(R ⁷ )S-, -CH(R ⁷ )N(R ⁸ )-, -CH(R ⁷ )N(C(O)R ⁸ )-, -CH(R ⁷ )N(C(O)OR ⁸ )-, -CH(R ⁷ )N(SO ₂ R ⁸ )-, -CH(R ⁷ )C(=NOR ⁸ )-, -CH(R ⁷ )C(O)-, -CH(R ⁷ )CH(OR ⁸ )-, -CH(R ⁷ )C(O)N(R ⁸ )-, -CH(R ⁷ )N(R ⁸ )C(O)-, -CH(R ⁷ )N(R ⁸ )S(O)-, -CH(R ⁷ )N(R ⁸ )S(O) ₂ -, -CH(R ⁷ )OC(O)N(R ⁸ )-, -CH(R ⁷ )N(R ⁸ )C(O)N(R ^7a )-, -CH(R ⁷ )NR ⁸ C(O)O-, -CH(R ⁷ )S(O)N(R ⁸ )-, -CH(R ⁷ )S(O) ₂ N(R ⁸ )-, -CH(R ⁷ )N(C(O)R ⁸ )S(O)-, -CH(R ⁷ )N(C(O)R ⁸ )S(O)-, -CH(R ⁷ )N(R ⁸ )S(O)N(R ^7a )-, -CH(R ⁷ )N(R ⁸ )S(O) ₂ N(R ^7a )-, -CH(R ⁷ )C(O)N(R ⁸ )C(O)-, -CH(R ⁷ )S(O)N(R ⁸ )C(O)-, -CH(R ⁷ )S(O) ₂ N(R ⁸ )C(O)-, -CH(R ⁷ )OS(O)N(R ⁸ )-, -CH(R ⁷ )OS(O) ₂ N(R ⁸ )-, -CH(R ⁷ )N(R ⁸ )S(O)O-, -CH(R ⁷ )N(R ⁸ )S(O) ₂ O-, -CH(R ⁷ )N(R ⁸ )S(O)C(O)-, -CH(R ⁷ )N(R ⁸ )S(O) ₂ C(O)-, -CH(R ⁷ )SON(C(O)R ⁸ )-, -CH(R ⁷ )SO ₂ N(C(O)R ⁸ )-, -CH(R ⁷ )N(R ⁸ )SON(R ^7a )-, -CH(R ⁷ )N(R ⁸ )SO ₂ N(R ^7a )-, -CH(R ⁷ )C(O)O-, -CH(R ⁷ )N(R ⁸ )P(OR ^7a )O-, -CH(R ⁷ )N(R ⁸ )P(OR ^7a )-, -CH(R ⁷ )N(R ⁸ )P(O)(OR ^7a )O-, -CH(R ⁷ )N(R ⁸ )P(O)(OR ^7a )-, -CH(R ⁷ )N(C(O)R ⁸ )P(OR ^7a )O-, -CH(R ⁷ )N(C(O)R ⁸ )P(OR ^7a )-, -CH(R ⁷ )N(C(O)R ⁸ )P(O)(OR ^7a )O-, or -CH(R ⁷ )N(C(O)R ⁸ )P(OR ^7a )-;

R ⁵ , R ⁶ , G ¹ ", and G ¹¹ " are each independently Co. _io alkyl, C ₂ ., ₀ alkenyl, C ₂ .,oalkynyl, Cj ioalkoxyCuioalkyl, Ci.ioalkoxyC ₂ .ioalkenyl, Ci. ₁₀ alkoxyC _2- ioalkynyl, Ci.ioalkylthioCi.ioalkyl, C ₁ . , ₀ alkylthioC _2- ιoalkenyl, C|.ioalkylthioC _2- ioalkynyl, cycloC ₃ _ _g alkyl, cycloC _3-g alkenyl, cycloC ₃ - _g alkylCi. _l oalkyl, cycloC ₃ . _g alkenylC|.ioalkyl, cycloC ₃ .galkylC _2- i ₀ alkenyl, cycloC ₃ .galkenylC ₂ .i ₀ alkenyl, cycloC _{3- g} alkylC ₂ _i ₀ alkynyl, cycloC ₃ . _g alkenylC _2- ioalkynyl, heterocyclyl-Ccioalkyl, heterocyclyl-C _2-l0 alkynyl, aryl-Co-ioalkyl, aryl-C _2-10 alkenyl, aryl-C ₂ .]oalkynyl, hetaryl-Co-ioalkyl, hetaryl-C _2- i _O alkenyl, or hetaryl-C ₂ _i _O alkynyl, any of which is optionally substituted with one or more independent halo, -CF ₃ , -OCF ₃ , -OR ⁷⁷ , -NR ⁷⁷ R ⁸⁷ , -C(O)R ⁷⁷ , -CO ₂ R ⁷⁷ , -CONR ⁷⁷ R ⁸⁷ , -NO ₂ , -CN, -S(O) _j 5aR ⁷⁷ , -SO ₂ NR ⁷⁷ R ⁸⁷ , -NR ⁷⁷ C(=O)R ⁸⁷ , -NR ⁷⁷ C(=O)OR ⁸⁷ , -NR ⁷⁷ C(O)NR ⁷⁸ R ⁸⁷ , -NR ⁷⁷ S (O) _j5a R ⁸⁷ , -C(=S)OR ⁷⁷ , -C(=O)SR ⁷⁷ , -NR ⁷⁷ C(=NR ⁸⁷ )NR ⁷⁸ R ⁸⁸ , -NR ⁷⁷ C(=NR ⁸⁷ )OR ⁷⁸ , -NR ⁷⁷ C(=NR ⁸⁷ )SR ⁷⁸ , -OC(=O)OR ⁷⁷ , -OC(=O)NR ⁷⁷ R ⁸⁷ , -OC(=O)SR ⁷⁷ , -SC(=O)OR ⁷⁷ , -P(O)OR ⁷⁷ OR ⁸⁷ , or -SC(=O)NR ⁷⁷ R ⁸⁷ substituents;

or R ⁵ with R ⁶ are optionally taken together with the carbon atom to which they are attached to form a 3-10 membered saturated or unsaturated ring, wherein said ring is optionally substituted with one or more independent R ⁶⁹ substituents and wherein said ring optionally includes one or more heteroatoms;

R ⁷ , R ^7a , and R ⁸ are each independently acyl, C _d oalkyl, C _2- i _O alkenyl, aryl, heteroaryl, heterocyclyl or cycloC ₃ _ _ι0 alkyl, any of which is optionally substituted by one or more independent G ¹¹¹ substituents;

R ⁴ is Co-ioalkyl, C ₂ .i ₀ alkenyl, C _2- ioalkynyl, aryl, heteroaryl, cycloC ₃ .| ₀ alkyl, heterocyclyl, cycloC _3- galkenyl, or heterocycloalkenyl, any of which is optionally substituted by one or more independent G ⁴¹ substituents;

R ⁶⁹ is halo, -OR ⁷⁸ , -SH, -NR ⁷⁸ R ⁸⁸ , -CO ₂ R ⁷⁸ , -C(=O)NR ⁷⁸ R ⁸⁸ , -NO ₂ , -CN, -S(O) _j8 R ⁷⁸ , -SO ₂ NR ⁷⁸ R ⁸⁸ , Co-ioalkyl, C ₂ _ ₁₀ alkenyl, C _2-10 alkynyl, C _M oalkoxyC^oalkyl, C,.,oalkoxyC ₂ .,oalkenyl, C _1- i ₀ alkoxyC _2- ιoalkynyl, C| _-10 alkylthioC|..ioalkyl, C) _-)0 alkylthioC ₂ .ioalkenyl, C].i ₀ alkylthioC _2- ioalkynyl, cycloC ₃ . ₈ alkyl, cycloC ₃ . ₈ alkenyl, cycloQ.galkylQ.ioalkyl, cycloC ₃ . _g alkylC ₂ . _l oalkenyl, cycloC ₃ . ₈ alkenylC ₂ . ₎₀ alkenyl, cycloC _3-8 alkylC _2- ioalkynyl, cycloC ₃ . _g alkenylC ₂ .| ₀ alkynyl, heterocyclyl-Co-ioalkyl, heterocyclyl-C _2- i ₀ alkenyl, or heterocyclyl-C _2- ioalkynyl, any of which is optionally substituted with one or more independent halo, cyano, nitro, -OR ⁷⁷⁸ , -SO ₂ NR ⁷⁷⁸ R ⁸⁸⁸ , or -NR ⁷⁷⁸ R ⁸⁸⁸ substituents; or R ⁶⁹ is aryl-Ccioalkyl, aryl-C ₂ . ₁₀ alkenyl, aryl-C _2- i ₀ alkynyl, hetaryl-Co-ioalkyl, hetaryl-C ₂ . _l oalkenyl, hetaryl-C ₂ .ioalkynyl, mono(C]. ₆ alkyl)aminoCi. ₆ alkyl, di(C| _-6 alkyl)aminoC|^alkyl, or -N(Ci _-6 alkyl)-C _)-6 alkyl-aryl, any of which is optionally substituted with one or more independent halo, cyano, nitro, -OR ⁷⁷⁸ , C _M oalkyl, C ₂ .i ₀ alkenyl, C ₂ .| _O alkynyl, haloCi.ioalkyl, haloC ₂ .i ₀ alkenyl, haloC _2-lo alkynyl, -COOH, -C(=O)NR ⁷⁷⁸ R ⁸⁸⁸ , -SO ₂ NR ⁷⁷⁸ R ⁸⁸⁸ , or -NR ⁷⁷⁸ R ⁸⁸⁸ substituents; or in the case Of -NR ⁷⁸ R ⁸⁸ , R ⁷⁸ and R ⁸⁸ are optionally taken together with the nitrogen atom to which they are attached to form a 3-10 membered saturated or unsaturated ring, wherein said ring is optionally substituted with one or more independent halo, cyano, hydroxy, nitro, Ci.ioalkoxy, -SO ₂ NR ⁷⁷⁸ R ⁸⁸⁸ , or -NR ⁷⁷⁸ R ⁸⁸⁸ substituents, and wherein said ring optionally includes one or more heteroatoms other than the nitrogen to which R ⁷⁸ and R ⁸⁸ are attached;

R ⁷⁷ , R ⁷⁸ , R ⁸⁷ , R ⁸⁸ , R ⁷⁷⁸ , and R ⁸⁸⁸ are each independently Q-ioalkyl, C _2-10 alkenyl, C ₂ . ₁₀ alkynyl, C _{1- 10} alkoxyCi.i ₀ alkyl, C _1-10 alkoxyC _2-10 alkenyl, C ₁ . ι ₀ alkylthioC _2- ioalkenyl, cycloC _3-8 alkyl, cycloC ₃ .galkenyl, cycloC _3-8 alkylCi. _l oalkyl, cycloC ₃ . ₈ alkylC _2- | ₀ alkenyl, cycloC _3-8 alkenylC _2-1 oalkenyl, cycloC _{3- 8} alkylC ₂ .ioalkynyl, cycloC ₃ . ₈ a]kenylC ₂ .ioalkynyl, heterocyclyl-Coooalkyl, heterocyclyl-C _2- ioalkenyl, heterocyclyl-C ₂ .i ₀ alkynyl, Ci.i ₀ alkylcarbonyl, C ₂ .|oalkenylcarbonyl, C ₂ .| ₀ alkynylcarbonyl, Q- ₁₀ alkoxycarbonyl, d.ioalkoxycarbonylCuoalkyl, monoCuβalkylaminocarbonyl, diCi-βalkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl, or

C| _-10 alkyl(aryl)aminocarbonyl, any of which is optionally substituted with one or more independent halo, cyano, hydroxy, nitro, Ci.ioalkoxy, -S0 ₂ N(Co- ₄ alkyl)(C _θJ »alkyl), or -N(Co^alkyl)(Co. ₄ alkyl) substituents;

or R ⁷⁷ , R ⁷⁸ , R ⁸⁷ , R ⁸⁸ , R ⁷⁷⁸ , and R ⁸⁸⁸ are each independently aryl-C _0- i _O alkyl, aryl-C ₂ -ioalkenyl, aryl-C _2- ioalkynyl, hetaryl-Co-ioalkyl, hetaryl-C ₂ . ₁₀ alkenyl, hetaryl-C ₂ .ioalkynyl, mono(Ci _-6 alkyl)aminoC| _-6 alkyl, diCCi.βalkytyaminoCi.βalkyi, mono(aryl)aminoCi _-6 alkyl, di(aryl)aminoC|. ₆ alkyl, or any of which is optionally substituted with one or more independent halo, cyano, nitro, -0(C( _M aIlCyI), Ci.ioalkyl, C ₂ . _)O alkenyl, C _2- ιoalkynyl, haloCi-ioalkyl, haloC _2- ιoalkenyl, haloC _2- ι ₀ alkynyl, -COOH, C _1-4 alkoxycarbonyl, -CON(Co- ₄ alkyl)(C ₀ -ioalkyl), -S0 ₂ N(Co- ₄ alkyl)(C _M alkyl), or -N(C ₀ ^alkyl)(Co- ₄ alkyl) substituents; n, m, jl , j la, j2a, j4, j4a, j5a, j7, andjδ are each independently 0, 1 , or 2; and aa and bb are each independently 0 or 1.

19. The method of claim 18 wherein the IGFR inhibitor is represented by Formula I

I or a pharmaceutically acceptable salt thereof, wherein: X ₁₁ X^ X ₄₁ X ₆ , and X ₇ are C; X ₃ and X ₅ are N;

Xι i, Xi2, Xi3. Xi4» and X ₎₅ are C;

R ¹ is cycloC ₃ .| ₀ alkyl optionally substituted by one or more independent G" substituents.

20. A method for treating cancer in a patient, comprising administering to said patient simultaneously or sequentially (i) a therapeutically or sub-therapeautically effective amount of an anticancer agent, or a pharmaceutically salt thereof; and (ii) a therapeutically or sub-therapeautically effective amount an IGFR inhibitor selected from the group consisting of:

3 -Cyclobutyl- 1 -(2-pyridin-2-ylquinolin-7-yl)-imidazo[ 1 ,5 -α]pyrazin-8-ylamine;

3-Cyclobutyl-l -(2-thiophen-2-ylquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-8-ylamine;

3-Cyclobutyl-l-(2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

[7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l -yl)-quinolin-2-yl]-phenylamine; l-(6-Chloro-2-phenylquinolin-7-yl)-3-cyclobutylimidazo[l,5-a]pyrazin-8-ylamine; l-(6-Chloro-2-pyridin-2-ylquinolin-7-yl)-3-cyclobutylimidazo[l,5-a]pyrazin-8-ylamine;

1 -(ό-Chloro^-thiophen-2-ylquinolin-V-yO-S-cyclobutylimidazot 1 ,5-a]pyrazin-8-ylamine; l-(6-Chloro-2-phenoxyquinolin-7-yl)-3-cyclobutylimidazo[l,5-a]pyrazin-8-ylamine;

[V^S-AminoO-cyclobutylimidazofl _j S-aJpyrazin-l-ylJ-ό-chloroquinolin-Z-ylJ-phenyl-amine;

3-Cyclobutyl- 1 -(8-fluoro-2-phenylquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-8-ylamine;

3-Cyclobutyl-l-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-imidazo[l ,5-a]pyrazin-8-ylamine;

3-Cyclobutyl-l-(8-fluoro-2-thiophen-2-ylquinolin-7-yl)-imidazo[l ,5-a]pyrazin-8-ylarnine;

3-Cyclobutyl- 1 -(8-fluoro-2-phenoxyquinolin-7-yl)-imidazo[ 1 ,5 -a]pyrazin-8-ylamine;

[T^δ-Amino-S-cyclobutylimidazofl _j S-alpyrazin-l-y^-S-fluoroquinolin-2-y^-phenyl-amine;

3-Cyclobutyl- 1 -(4-methyl-2-phenylquino1in-7-yl)-imidazo[ 1 ,5-a]pyrazin-8-ylamine;

3-Cyclobutyl-l-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

3-Cyclobutyl- l-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

[7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l-yl)-4-methylquinolin-2-yl]-phenylamine;

3-Cyclobutyl- 1 -(4-methyl-2-phenoxyquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-8-ylamine;

[y^S-Amino-S-cyclobutylimidazofl .S-aJpyrazin-l -yl^-phenylquinolin^-yll-methylamine;

[7-(8-Amino-3-cyclobutylimidazo[ 1 ,5-a]pyrazin- 1 -yl)-2-pyridin-2-ylquinolin-4-yl]-methylamine;

[7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l -yl)-2-thiophen-2-ylquinolin-4-yl]-methylamine;

[7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l -yl)-2-phenoxyquinolin-4-yl]-methylamiτie;

7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l-yl)-N ⁴ -methyl-N ² -phenylquinoline-2,4-diamine;

S-fδ-Amino-l^-pyridin-2-ylquinolin^-y^-imidazofl.S-aJpyrazin-S-y^-cyclobutanol;

3-[8-Amino-l-(2-thiophen-2-ylquinolin-7-yl)-imidazo[l ,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l -(2-phenoxyquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(2-phenylaminoquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(6-chloro-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(6-chloro-2-phenylaminoquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l -(6-chloro-2-phenoxyquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(8-fluoro-2-thiophen-2-y]quinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

S-fS-Amino-l-CS-fluoro^-phenoxyquinolin^-y^-imidazofl jS-aJpyrazinO-y^-cyclobutanol;

3-[8-Amino-l -(8-fluoro-2-phenylaminoquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(8-fluoro-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutaπol;

3-[8-Amino-l-(8-fluoro-4-methyl-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(8-fluoro-4-methyl-2-thiophen-2-yl-quinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclobutanol;

3-[8-Aτnino-l-(8-fluoro-4-methyl-2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclobutanol;

3-[8-Amino-l-(8-fluoro-4-methyl-2-pheny]aminoquinolm-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclobutanol;

3-[8-Amino-l-(8-fluoro-4-methyl-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol,

S-CS-Azetidin-l-ylmethylcyclobutylJ-l^-pyridm^-ylquinohn-7-yO-imidazotl.S-aJpyrazin-δ-ylamine;

S^-Azetidiπ-l-ylmethylcyclobutyO-l^-thiophen^-ylquinolin-V-yO-imidazofl _j S-alpyrazin-S-ylamme,

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(2-phenoxyquinolm-7-yl)-imidazo[l,5-a]pyrazin-8-yIamine;

{7-[8-Amino-3 -(3 -azetidin- 1 -ylmethylcyclobutyl)-imidazo[ 1 ,5 -a]pyrazin- 1 -yl] -qumolin-2-yl } - phenylamine,

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(6-chloro-2-phenylquinohn-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(6-chloro-2-pyndm-2-yl-quinolin-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(6-chloro-2-thiophen-2-yl-quinohn-7-yl)-imidazo[l,5-a]pyrazin-

8-ylamine;

{7-[8-Amino-3-(3-azetidin-l-ylmethylcyclobutyl)-imidazo[l,5-a]pyrazin-l-yl]-6-chloro-quinolin-2-yl}- phenylamine,

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(6-chloro-2-phenoxyquinohn-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(4-methyl-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

S-CS-Azetidin-l-ylmethylcyclobutyO-l^-methyl^-pyridin-2-ylqumolin^-yO-imidazofl.S-alpyrazin-S- ylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-

8-ylamme,

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(4-methyl-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

{7-[8-Amino-3-(3-azetidin-l-ylmethylcyclobutyl)-imidazo[l,5-a]pyrazin-l-yl]-4-methyl-qumolin-2-yl}- phenyl-amine,

3-(3-Dimethylaminomethylcyclobutyl)-l-(2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

3-(3-Dimethylaminomethylcyclobutyl)-l-(2-pyridin-2-ylquinolιn-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine,

3-(3-Dimethylammomethylcyclobutyl)-l-(2-thiophen-2-ylquinolm-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

{7-[8-Amino-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l,5-a]pyrazin-l-yl]-quino]in-2-y]}- phenylamine,

3-(3-Dimethylaminomethylcyclobutyl)-l-(2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamme; l-(6-Chloro-2-phenylquinolin-7-yl)-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l ,5-a]pyrazin-8- ylamine,

l-(6-Chloro-2-pyridin-2-ylquinolin-7-yl)-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l,5-a]pyrazin-

8-ylamine; l^ό-Chloro^-thiophen-2-ylquinolin-V-yO-S^S-dimethylaminomethylcyclobuty^-imidazotl.S-aJpyrazin-

8-ylamine; l-(6-Chloro-2-phenoxyquinolin-7-yl)-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l,5-a]pyrazin-8- ylamine;

{7-[8-Amino-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l,5-a]pyrazin-l-yl]-6-chloroquinolin-2-yl}- phenyl amine;

S-CS-DimethylaminomethylcyclobutylJ-l^-methyl^-phenylquinolin-V-y^-imidazofl.S-aJpyrazin-S- ylamine;

S-CS-DimethylaminomethylcyclobutyO-l^-methyl^-pyridin-2-ylquinolin-7-y^-imidazofl.S^pyrazin-

8-ylamine;

3-(3 -Dimethylaminomethylcyclobutyl)-1 -(4-methyl-2-thiophen-2-ylquinolin-7-yl)-imidazo[l ,5- a]pyrazin-8-ylamine;

{7-[8-Amino-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l,5-a]pyrazin-l-yl]-4-methylquinolin-2- yl } -phenylamine ;

3-(3-Dimethylaminomethylcyclobutyl)-l-(4-methyl-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

4-[8-Amino- 1 -(2-pyridin-2-ylquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l -(2-phenylaminoquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(6-chloro-2-phenylquinolin-7-yl)-imidazo[l ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l -(6-chloro-2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclohexanecarboxylic acid amide;

4-[8-Amino-l -(6-chloro-2-phenylaminoquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-3-yl]- cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(6-chloro-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l -(4-methyl-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Ammo-l-(4-methyl-2-pyπdin-2-ylquinolin-7-yl)-irτπdazo[l,5-a]pyrazin-3-yl]- cyclohexanecarboxyhc acid amide;

4-[8-Amino-l-(4-methyl-2-miophen-2-ylquinohn-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclohexanecarboxyhc acid amide;

4-[8-Amino-l-(4-methyl-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxyhc acid amide,

4-[8-Amino-l-(4-methyl-2-phenylaminoquinolin-7-yl)-imidazo[l,5-a]pyrazm-3-yl]- cyclohexanecarboxyhc acid amide;

4-[8-Amino-l-(2-pyndin-2-ylquinohn-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylamide;

4-[8-Amino-l-(2-thiophen-2-ylquinohn-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylamide,

4-[8-Amino-l-(2-phenylaminoquinolin-7-yl)-imidazo[l,5-a]pyrazm-3-yl]-cyclohexanecarboxyhc acid methylamide;

4-[8-Amino-l-(2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylamide,

S^-Aminomethylcyclohexy^-l^Z-pyridin-2-ylquinolin^-ylJ-imidazofl.S-ajpyrazin-S-ylamine;

S^-AminomethylcyclohexyO-l^-thiophen-2-ylquinolin^-y^-imidazofl .S-aJpyrazin-δ-ylamme,

3-(4-Aminomethylcyclohexyl)-l-(2-phenoxyquinohn-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

{7-[8-Amino-3-(4-ammomethylcyclohexyl)-imidazo[l,5-a]pyrazin-l-yl]-quinohn-2-yl}-phenylamine,

7-Cyclobutyl-5-(2-phenylquinohn-7-yl)-7H-pyτrolo[2,3-d]pyrimidin-4-ylamine;

7-Cyclobutyl-5-(2-pyπdin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-Cyclobutyl-5-(2-thiophen-2-ylquinohn-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine,

[7-(4-Amino-7-cyclobutyl-7H-pyrrolo[2,3-d]pynmidin-5-yl)-quinolin-2-yl]-phenylamine;

7-Cyclobutyl-5-(2-phenoxyquinohn-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

5-(6-Chloro-2-phenylquinolin-7-yl)-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

5-(6-Chloro-2-pyπdin-2-ylquinohn-7-yl)-7-cyclobutyl-7H-pyrrolo[2,3-d]pyπmidin-4-ylamine;

5-(6-Chloro-2-thiophen-2-ylquinohn-7-yl)-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

5-(6-Chloro-2-phenoxyquinolin-7-yl)-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

[7-(4-Amino-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidm-5-yl)-6-chloroquinohn-2-yl]-phenylamine;

3-[4-Amino-5-(2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2 _J 3-d]pyrimidin-7-yl]-cyclobutanol,

3-[4-Amino-5-(2-pyridin-2-ylquiπolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(2-phenylaminoquinohn-7-yl)-pyrrolo[2,3-d]pyπmidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(2-phenoxyquinolin-7-yl)-pyiτolo[2,3-d]pyπmidin-7-yl]-cyclobutanol,

3-[4-Amino-5-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyπmidin-7-yl]-cyclobutanol,

3-[4-Amino-5-(6-chloro-2-phenylquinohn-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol,

3-[4-Amino-5-(6-chloro-2-phenoxyquinohn-7-yl)-pyrrolo[2,3-d]pyπmidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(6-chloro-2-phenylaminoqumohn-7-yl)-pyrrolo[2,3-d]pyrimidιn-7-yl]-cyclobutanol,

3.[4-Amino-5-(8-fluoro-2-pheny]quinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(8-fluoro-2-thiophen-2-ylquinolm-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-pyiτolo[2,3-d]pyriπiidiπ-7-yl]-cyclobutanol,

3-[4-Amino-5-(8-fluoro-2-phenylaminoquinolin-7-yl)-pyττolo[2,3-d]pyπmidin-7-yl]-cyclobutanol,

3-[4-Amino-5-(8-fluoro-2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyriniidin-7-yl]-cyclobutanol;

7-Cyclobutyl-5-(8-fluoro-2-phenylquinohn-7-yl)-7H-pyrrolo[2,3-d]pyriπiidin-4-ylamine;

7-Cyc1obutyl-5-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidm-4-ylamine,

7-Cyclobutyl-5-(8-fluoro-2-thiophen-2-yl-quinolin-7-yl)-7H-pyrrolo[2,3-d]pyπmidin-4-ylamine,

7-Cyclobutyl-5-(8-fluoro-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

[7-(4-Amino-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-8-fluoroqumohn-2-yl]-phenylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-phenylquinohn-7-yl)-7H-pyrrolo[2,3-d]pyπmidin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-pyπdin-2-ylquinohn-7-yl)-7H-pyrrolo[2,3-d]pyπmidin-4- ylamme;

7-(3-Azctidin-l-ylmethylcyclobutyl)-5-(2-thiophen-2-yl-quinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamme;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyπmidin-5-yl]-quinohn-2-yl} - phenylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-phenoxyqumolin-7-yl)-7H-pyrro]o[2,3-d]pyr]midin-4-ylamine,

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(6-chloro-2-pyndin-2-ylquinoljn-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(6-chloro-2-phenylquinolin-7-yl)-7H-pyrτolo[2,3-d]pyπmidin-4- ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(6-chloro-2-thiophen-2-ylquinohn-7-yl)-7H-pyrrolo[2,3- d]pyπmidin-4-ylamine,

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(6-chloro-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyπmidin-

4-ylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcycIobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-6-chloroqutnolin-2- yl} -phenylamme;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(8-fluoro-2-phenylquinolm-7-yl)-7H-pyiτolo[2,3-d]pyπmidιn-4- ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(8-fluoro-2-pyπdin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- djpyrimidin^-ylamme,

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(8-fluoro-2-thiophen-2-ylquinoltn-7-yl)-7H-ρyrrolo[2 _> 3- d]pyrimidin-4-ylamine,

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-8-fluoroquinohn-2- yl} -phenyl-amine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(8-fluoro-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-

4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(4-rnethyl-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(4-τnethyl-2-thiophen-2-ylquinolin-7-yl)-7H-pyrτolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(4-methyl-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-

4-ylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyriτnidin-5-yl]-4-methylquinolin-2- yl } -phenylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-phenylquinolin-4- yl } -methylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-pyridin-2- ylquinolin-4-yl} -methylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyiτolo[2,3-d]pyrimidin-5-yl]-2-thiophen-2- ylquinolin-4-yl} -methylamine;

7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-<flpyrimidin-5-yl]-λ' ⁴ -methyl-N ² - phenylquinoline-2,4-diamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-phenoxyquinolin-

4-yl} -methylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(3-DimethylaminomethyIcyclobutyl)-5-(2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

{7-[4-Amino-7-(3-dimethylaminomethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-quinolin-2-yl}- phenylamine;

5-(6-Chloro-2-phenylquinoliπ-7-yl)-7-(3-dimethylaminomethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-

4-ylamine;

5-(6-Chloro-2-pyridin-2-ylquinolin-7-yl)-7-(3-dimethylaminomethylcyclobutyl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

5-(6-Chloro-2-thiophen-2-ylquinolin-7-yl)-7-(3-dimethylaminomethylcyclobutyl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

{7-[4-Amino-7-(3-dirnethylaminomethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-6-chloroquinolin-

2-yl } -phenylamine;

5-(6-Chloro-2-phenoxyquinolin-7-yl)-7-(3-dimethylaminomethylcyclobutyl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(8-fluoro-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-

4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(8-fluoro-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(8-fluoro-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(4-methyl-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-

4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-y1amine;

7-{3-Dimethylaminomethylcyclobutyl)-5-(4-methyl-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

4-[4-Amino-5-(2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(2-pyridin-2-y]quinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(2-pyridin-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(6-chloro-2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(6-chloro-2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

7-(4-Aminomethylcyclohexyl)-5-(2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-chloro-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-chloro-2-phenylquinolin-7-yl)-7H-pyrτolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(4-methyl-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(4-methyl-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-AminomethylcyclohexyI)-5-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(2-pyridin-2-yl-quinolin-7-yl)-lH-pyrazolo[3,4-d]ρyrimidin-4-ylamine; l -(4-Aminomethylcyclohexyl)-3-(2-ρhenoxyquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine;

l-(4-Aminomethylcyclohexyl)-3-(2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine; l-(4-Aminomethylcyclohexyl)-3-(6-chloro-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-

4-ylamine; l-(4-Aminomethylcyclohexyl)-3-(6-chloro-2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine;

1 -(4-Aminomethylcyclohexyl)-3 -(4-methyl-2-thiophen-2-ylquinolin-7-yl)- 1 H-pyrazolo[3 ,4-d]pyrimidin-

4-ylamine; l-(4-Aminomethylcyclohexyl)-3-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l^-Aminomethylcyclohexy^^^-methyl^-phenoxyquinolin^-ylJ-lH-pyrazolofS^-dJpyrimidin^- ylamine; l-(4-Aminomethylcyclohexyl)-3-(4-methyl-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l^-Aminomethylcyclohexyl^^S-fluoro^-thiophen-l-yl-quinolin^-y^-lH-pyrazolofS^-dJpyrimidin-

4-ylamine; l-(4-Aminomethylcyclohexyl)-3-(8-fluoro-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine;

1 -(4-Aminomethylcyclohexyl)-3 -(8-fluoro-2-phenoxyquinolin-7-yl)- 1 H-pyrazolo[3 ,4-d]pyrimidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine;

4-[4-Amino-3-(2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin- 1 -yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(6-chloro-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l -yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pynmidin-l-yl]- cyclohexanecarboxylic acid amide,

4-[4-Amino-3-(6-chloro-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxyhc acid amide, 4-[4-Amino-3-(8-fluoro-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyπmidin-l-yl]-cyclohexanecarboxyhc acid amide,

4-[4-Amino-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyπmidm-l-yl]- cyclohexanecarboxyhc acid amide,

4-[4-Amino-3-(8-fluoro-2-pyπdin-2-ylquinohn-7-yl)-pyrazolof3,4-d]pyπmidin-l-yl]- cyclohexanecarboxyhc acid amide,

4-[4-Amino-3-(8-fluoro-2-phenoxyquinohn-7-yl)-pyrazolo[3,4-d]pyπmidin-l-yl]-cyclohexanecarboxylic acid amide,

4-[4-Amino-3-(4-methyl-2-phenylquinohn-7-yl)-pyrazolo[3,4-d]pyπmidin-l-yl]-cyclohexanecarboxylic acid amide,

4-[4-Amino-3 -(4-methyl-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3 ,4-d]pyrimidm- 1 -yl] - cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(4-methyl-2-pyπdin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyπmidin-l-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(4-mcthyl-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxyhc acid amide;

4-[4-Amino-3-(2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(2-phenylquinohn-7-yl)-pyrazolo[3,4-d]pyπmidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-y]]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(2-phenoxyquinohn-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(6-chloro-2-phenylquinolm-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxyhc acid methylamide;

4-[4-Amino-3-(6-chloro-2-thiophen-2-ylquinohn-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxyhc acid methylamide;

4-[4-Ammo-3-(6-chloro-2-phenoxyquinohn-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(8-fluoro-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pynmidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid methylamide; 4-[4-Amino-3-(8-fluoro-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidm-l-yl]-cyclohexanecarboxylic acid methylamide; 4-[4-Amino-3-(4-methyl-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(4-methyl-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid methylamide;

1 -Cyclobutyl-3 -(2-thiophen-2-ylquinolin-7-yl)- 1 H-pyrazolo[3 ,4-d]ρyrimidin-4-ylamine; l-Cyclobutyl^^-phenylquinolin^-y^-lH-pyrazolofS^-dJpyrimidin^-ylamine;

1 -Cyclobutyl-3 -(2 -phenoxyquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine; l-Cyclobutyl-3-(2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine;

3-(6-Chloro-2-phenylquinolin-7-yl)-l-cyclobutyl-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine;

3-(6-Chloro-2-pyridin-2-ylquinolin-7-yl)-l-cyclobutyl-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine;

3-(6-Chloro-2-thiophen-2-ylquinolin-7-yl)-l-cyclobutyl-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine;

3-(6-Chloro-2-phenoxyquinolin-7-yl)-l-cyclobutyl-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine; l-Cyclobutyl^^-methyl^-thiophen-2-ylquinolin^-y^-lH-pyrazolotS^-djpyrimidin^-ylamine; l-Cyclobutyl-S^-methyl^-pyridin-2-ylquinolin^-ylJ-lH-pyrazolofS^-dJpyrimidin^-ylamine; l-Cyclobutyl-3-(4-methyl-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine;

1 -Cyclobutyl-3 -(4-methyl-2-phenoxyquinolin-7-yl)- 1 H-pyrazolo[3 ,4-d]pyrimidin-4-ylamine; 3-[4-AminoO^-phenylquinolin-7-yl)-pyrazolofS^-djpyrimidin-l-ylJ-cyclobutanol;

3-[4-Amino-3-(2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol; 3-[4-Amino-S^-thiophen-2-ylquinolin^-ylJ-pyrazoloIS^^pyrimidin-l-y^-cyclobutanol;

3-[4-Amino-3-(2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l -yl]-cyclobutanol;

3-[4-Amino-3-(6-chloro-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3 -(6-chloro-2-phenoxyquinolin-7-yl)-pyrazolo [3 ,4-d]pyrimidin- 1 -yl] -cyclobutanol ;

3-[4-Amino-3-(4-methyl-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(4-methyl-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

l-(3-Azetidin-l-ylmethylcyclobutyl)-3-(2-pyπdin-2-ylquinohn-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(3-Azetidin-l-ylmethylcyclobutyl)-3-(2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyπmidiπ-4-ylamine; l^-Azetidin-l-ylmethylcyclobutyO-S^-thiophen-2-ylquinohn-7-yO-lH-pyrazolotS^-dJpyrimidin^- ylamine;

1 -(3 -Azetidin- 1 -ylmethylcyclobutyl)-3-(2-phenoxyquinohn-7-yl)- 1 H-pyrazolo[3 ,4-d]pynmidin-4- ylamine; l-(3-Azetidm-l-ylmethylcyclobutyl)-3-(6-chloro-2-thiophen-2-ylqumohn-7-yl)-lH-pyrazolo[3,4- d]pyrιmidin-4-ylamine; l-(3-Azetidin-l-ylmethylcyclobutyl)-3-(6-chloro-2-phenylquinolin-7-yl)-lH-pyrazolo[3 ₎ 4-d]pyrimidin-4- ylamine; l-(3-Azetidin-l-ylmethylcyclobutyl)-3-(6-ch]oro-2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4-d]pyπmidin-

4-ylamine, l-(3-Azetidin-l-ylτnethylcyclobutyl)-3-(6-chloro-2-pyridin-2-ylqumohn-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine;

1 -(3-Azetidm-l -ylmethylcyclobutyl)-3-(4-methyl-2-pyπdm-2-ylquinolm-7-yl)-l H-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-CS-Azetidin-l-ylmethylcyclobutyOO^-methyl^-phenylquinohn^-ylJ-lH-pyrazolofS^-dJpyrimidin-

4-ylamine, l-CS-Azetidin-l-ylmethylcyclobutyO-S^-methyl^-thiophen-2-ylquinohn^-y^-lH-pyrazoloP^- d]pyπmidin-4-ylamine, l-(3-Azetidm-l -ylmethylcyclobutyl)-3-(4-methyl-2-phenoxyquinohn-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyπmidin-4- ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-{2-thiophen-2-ylquinohn-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pynmidin-4- ylamine; l-CS-Dimethylaminomethylcyclobuty^^^-phenoxyquinohn^-yO-lH-pyrazolofS^-dlpyrimidin^- ylamine;

3-(6-Chloro-2-phenylquinohn-7-yl)-l-(3-dimethylaminomethylcyclobutyl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine;

3-(6-Chloro-2-thiophen-2-ylquinohn-7-yl)-l-(3-dimethylaminomethylcyclobutyl)-lH-pyrazolo[3,4- d]pyπmidin-4-ylamine;

3-(6-Chloro-2-phenoxyquinohn-7-yl)-l-(3-dimethylaminomethylcyclobutyl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine;

3-(6-Chloro-2-pyridin-2-ylquinolin-7-yl)-l-(3-dimethylaminomethylcyclobutyl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-CS-DimethylaminomethylcyclobutylJ-S^-methyl^-pyridin-2-ylquinolin-y-yO-lH-pyrazoloP^- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(4-methyl-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine;

1 -(3 -Dimethylaminomethylcyclobutyl)-3-(4-methyl -2-phenoxyquinolin-7-yl)- 1 H-pyrazolo[3 ,4- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(8-fluoro-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-

4-ylamine; l -(3-Dimethylaminomethylcyclobutyl)-3-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(8-fluoro-2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(8-fluoro-2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine;

3-Cyclobutyl-l-(3-phenylquinoxalin-6-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

3-[8-Amino-l-(3-phenylquinoxalin-6-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(3-phenylquiπoxalin-6-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

4-[8-Amino-l -(3-phenylquinoxalin-6-yl)-imidazo[l ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l -(3-phenylquinoxalin-6-yl)-imidazo[l ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylatnide;

4-[8-Amino-l-(2-phenylquinazolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(2-phenylquinazolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylamide;

3-Cyclobutyl-l-(2-phenylquinazolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

3-[8-Amino-l-(2-phenylquinazolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(2-phenylquinazolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

3-[3-(2-Methoxyethoxy)-cyclobutyl]-l -(2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

1 -(6-Chloro-2-phenylquinolin-7-yl)-3-[3-(2-methoxyethoxy)-cyclobutyl]-imidazo[ 1 ,5-a]pyrazin-8- ylamine;

3-[3-(2-Methoxyethoxy)-cyclobuty ^] ]-l-(4-methyl-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

3-(l-Methyl-l,2,3,6-tetrahydropyridin-4-yl)-l-(2-phenylquinolin-7-yl)-imidazo[l ₎ 5-a]pyrazin-8-ylamine; l-{4-[8-Amino-l -(2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-3,6-dihydro-2H-pyridin-l-yl}- ethanone;

3-Bicyclo[3.1 0]hex-6-yl-l-(2-ρhenylquinohn-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine,

6-[8-Amino-l-(2-phenylquinohn-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-bicyclo[3.1.0]hexan-3-ol,

7-Cyclobutyl-5 -(2-phenylquinol in-7-yl)-imidazo[5, 1 -f] [ 1 ,2,4]tπazin-4-ylamme,

7-Cyclobutyl-5 -(2-thiophen-2-ylquinohn-7-yl)-imidazo[5 , 1 -f] [ 1 ,2,4]triazin-4-ylamine;

7-Cyclobutyl-5 -(2-phenoxyquinohn-7-yl)-imidazo[5 , 1 -f] [ 1 ,2,4]tπazin-4-ylamine;

7-Cyclobutyl-5 -(2-pyridm-2-ylquinohn-7-yl)-imidazo[5 , 1 -f] [ 1 ,2,4]tπazin-4-ylamine,

3-[4-Amino-5-(2-phenylquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-7-yl]-cyclobutanol,

3-[4-Amino-5-(2-thiophen-2-ylquinolin-7-yl)-imidazo[5,l-f][l,2,4]tπazin-7-yl3-cyclobutanol;

3-[4-Ammo-5-(2φhenoxyqumohn-7-yl)^midazo[5,l-f][l,2,4]tnazm-7-yl]^yclobutanol;

3-[4-Amino-5-(2-pyridin-2-ylquinolm-7-yl)-imidazo[5, 1 -f][l ,2,4]tnazin-7-yl]-cyclobutanol,

7-(3-Azetidin-l -ylmethylcyclobutyO-5-(2-phenylquinolin^-yO-imidazotS, 1 -f][l ,2,4]tπazm-4-ylamine,

7-(3-Azetidin-l -ylmethylcyclobutyl)-5-(2-thiophen-2-ylquinolm-7-yl)-imidazo[5, 1 -f] [ 1 ,2,4]tnazin-4- ylamme,

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-phenoxyquinohn-7-yl)-imidazo[5,l-f][l,2 _> 4]triazin-4-ylamine,

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-pyπdin-2-ylquinolin-7-yl)-imidazo[5,l-fl[l,2,4]tπazin-4- ylamine;

7-(3-Dimethylammomethylcyclobutyl)-5-(2-pyπdin-2-ylquinolin-7-yl)-imidazo[5,l-f|[l,2,4]tπazm-4- ylamine,

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-thiophen-2-ylquinolin-7-yl)-imidazo[5,l-f][l ₎ 2,4]triazin-4- ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-phenylquinolin-7-yl)-imidazo[5,l-f][l,2,4]tπazin-4-ylamine,

7-(3-Dimethylammomethylcyclobutyl)-5-(2-phenoxyquinolin-7-yl)-imidazo[5,l-f][l,2,4]tπazin-4- ylamine,

4-[4-Amino-5-(2-phenylquinohn-7-yl)-imidazo[5,l-f][l,2,4]tnazin-7-yl]-cyclohexanecarboxylic acid amide,

4-[4-Amino-5-(2-thiophen-2-ylquinohn-7-yl)-imidazo[5, l-f][l,2,4]tπazin-7-yl]-cyclohexanecarboxylic acid amide,

4-[4-Amino-5-(2-phenoxyquinohn-7-yl)-imidazo[5, l-f][ 1 ,2,4]tπazin-7-yl]-cyclohexanecarboxyiic acid amide,

4-[4-Amino-5-(2-phenylquinolm-7-yl)-imidazo[5,l-f][l ₎ 2,4]tπazin-7-yl]-cyclohexanecarboxylic acid methylamide,

4-[4-Amino-5-(2-thiophen-2-ylquinohn-7-yl)-imidazo[5,l-f][l ,2,4]tnazin-7-yl]-cyclohexanecarboxyhc acid methylamide,

4-[4-Amino-5-(2-phenoxyquinohn-7-yl)-imidazo[5,l-f][l,2,4]tnazin-7-yl]-cyclohexanecarboxylic acid methylamide;

7-(4-Aminomethylcyclohexyl)-5-(2-phenylquinohn-7-yl)-imidazo[5,l-f][l _J 2,4]tnazin-4-ylamine,

7-(4-Aminomethylcyclohexyl)-5-(2-thiophen-2-ylquinohn-7-yl)-imidazo[5,l-f][l,2,4]tnazin-4-ylamine,

7-(4-Aminomethylcyclohexyl)-5-(2-phenoxyquinohn-7-yl)-imidazo[5,l-f][l,2,4]tπazin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-ch]oro-2-phenylquinohn-7-yl)-imidazo[5, 1 -fj[l ,2,4]tnazin-4- ylamine;

4-[4-Amino-5-(6-chloro-2-phenylquinolin-7-yl)-imidazo[5,l-f|[l,2,4]tπazin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(6-chloro-2-phenylquinolin-7-yl)-imidazo[5,l-f][l,2,4]tπazin-7-yl]-cyclohexanecarboxylic acid methylamide;

5-(6-Chloro-2-phenylquinolin-7-yl)-7-cyclobutyhmidazo[5,l-f][l ,2,4]tπazin-4-ylamine;

3-[4-Amino-5-(6-chloro-2-phenylquinohn-7-yl)-imidazo[5,l-fl[l,2,4]tπazin-7-yl]-cyclobutanol;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(6-chIoro-2-phenylquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-4- ylamine;

7-(3-Azetidin-l-ylrnethylcyclobutyl)-5-(2-phenylquinohn-7-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-ylamine,

3-[4-Amino-5-(2-phenylquinolin-7-yl)-5H-pyrrolo[3,2-d]pynmidin-7-yl]-cyclobutanol;

7-Cyclobutyl-5-(2-phenylquinolin-7-yl)-5H-pyrrolo[3,2-d]pyπmidm-4-ylamine,

7-Phenyl-5-(2-phenylquinolin-7-yl)-7H-pyrτolo[2,3-d]pyrimidm-4-ylamine;

3-Isopropyl-l-(2-phenylqumolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

3 -tert-Butyl- 1 -(2 -phenylqumolin-7 -yl)-imidazo [ 1 ,5 -a]pyrazin-8-ylamine ;

5-[8-Ammo-l-(2-phenylqumohn-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-pyrrolidin-3-ol,

3-Cyclobutyl-l-(2-phenylquinohn-7-yl)-2H-imidazo[l,5-α]pyrazin-8-ylamme; trans- 4-[8-Amino-l -(2-phenylquinohn-7-yl)-imidazo[l ,5-α]pyrazin-3-yl]-cyclohexanecarboxyhc acid amide,

/rα/i5-4-[8-Amino-l-(2-phenylquinohn-7-yl)-imidazo[l,5-α]pyrazin-3-yl]-cyclohexanecarboxylic acid methyl ester;

/rα«5-4-[8-Amino-l-(2-phenylquinolin-7-yl)-imidazo[l,5-α]pyrazin-3-yl]-cyclohexanecarboxyhc acid, frα«.s-4-[8-Amino-l -(2-phenylquinolm-7-yl)-imidazo[ 1 ,5-α]pyrazin-3-yl]-cyclohexanecarboxyhc acid methylamide,

/rα/jj-{4-[8-Amino-l(2-phenylquinolm-7-yl)-imidazo[l ,5-α]pyrazin-3-yl]-cyclohexyl}-methanol,

/rαπ5-2-{4-[8-Amino-l-(2-phenylquinoliπ-7-yl)-imidazo[l ,5-α]pyrazin-3-yl]-cyclohexylmethyl}- isoindole-l,3-dione;

3-(4-Aminomethyl-cyclohexyl)-l-(2-phenyl-quinohn-7-yl)-imidazo[l ,5-a] pyrazin-8-ylamine;

/ran5-3-(4-Aminomethylcyclohexyl)-l-(2-phenylquinohn-7-yl)-imidazo[l ,5-a] pyrazin-8-ylamme;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(2-phenylquinohn-7-yl)-imidazo[l,5-α]pyrazin-8-ylamine; c«-3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(2-phenylquinolin-7-yl)-imidazo[l ,5-a]pyrazin-8-ylamine;

{3-[8-Amino-l-(2-phenylquinohn-7-yl)-imidazo[l,5-α]pyrazin-3-yl]-cyclobutyl} -methanol, and

«5-3-[3-(4-Methyl-piperazin-l-yl)-cyclobutyl]l-(2-phenyl-quinohn-7-yl)-imidazo[l ,5-a]pyrazin-8- ylamine)

21 The method of claim 18, wherein the anti-cancer agent is an EGFR kinase inhibitor, MEK inhibitor, VEGFR inhibitor, anti-VEGFR2 antibody, KDR antibody, AKT inhibitor, PDK-I inhibitor,

PI3K inhibitor, c-kit/Kdr tyrosine kinase inhibitor, Bcr-Abl tyrosine kinase inhibitor, VEGFR2 inhibitor, PDGFR-beta inhibitor, KIT inhibitor, Flt3 tyrosine kinase inhibitor, PDGF receptor family inhibitor, Flt3 tyrosine kinase inhibitor, RET tyrosine kinase receptor family inhibitor, VEGF-3 receptor antagonist, Raf protein kinase family inhibitor, angiogenesis inhibitor, Erb2 inhibitor, mTOR inhibitor, IGF-IR antibody, NFkB inhibitor, Proteosome inhibitor, chemotherapy agent, or glucose reduction agent.

22. The method of claim 18, wherein the anti-cancer agent is ARRY-142886, PD-184352, ZD- 6474, IMC-1121b, CDP-791, imatinib, sunitinib malate, sorafenib, PTK-787, lapatinib, sirolimus, temsirolimus, everolimus, CP-751871 , RAV-12, IMC-A12, 19D12, PS-1 145, orbortezomib.

23. The method of claim 21, wherein the anti-cancer agent is an EGFR inhibitor.

24. The method of claim 23, wherein the EGFR kinase inhibitor is erlotinib, cetuximab, gefitinib, or a salt thereof.

25. The method of claim 24, wherein the EGFR kinase inhibitor is erlotinib or a salt thereof.

26. The method of claim 20, wherein the anti-cancer agent is erlotinib or a salt thereof.

27. The method of claim 25, wherein the patient is a human that is being treated for cancer.

28. The method of claim 27, wherein the cancer is colorectal cancer, non-small cell lung carcinoma, pancreatic cancer, head and neck cancer, breast cancer, or neuroblastma.

29. The method of claim 28, wherein the cancer is colorectal cancer or non-small cell lung carcinoma.

30. The method of claim 27, wherein erlotinib and the IGFR inhibitor are co-administered to the patient in the same formulation.

31. The method of claim 27, wherein erlotinib and the IGFR inhibitor are co-administered to the patient in different formulations.

32. The method of claim 27, wherein erlotinib and the IGFR inhibitor are co-administered to the patient by the same route.

33. The method of claim 27, wherein erlotinib and the IGFR inhibitor are co-administered to the patient by different routes.

34 The method of claim 27, wherein erlotinib is administered to the patient by parenteral or oral administration.

35. The method of claim 27, wherein the IGFR inhibitor is administered to the patient by parenteral administration

36 The method of claim 27, additionally compπsing one or more other anti-cancer agents.

37. The method of claim 36, wherein the other anti-cancer agents are selected from an alkylating agent, cyclophosphamide, chlorambucil, cisplatin, busulfan, melphalan, carmusnne, streptozotocin, tnethylenemelamine, mitomycin C, an anti-metabolite, methotrexate, etoposide, 6-mercaptopuπne, 6- thiocguanme, cytarabine, 5-fluorouracil, raltitrexed, capecitabine, dacarbazine, an antibiotic, actinomycin D, doxorubicin, daunorubicm, bleomycin, mithramycin, an alkaloid, vinblastine, paclitaxel, a glucocorticoid, dexamethasone, a corticosteroid, prednisone, a nucleoside enzyme inhibitors, hydroxyurea, an amino acid depleting enzyme, asparaginase, folinic acid, leucovoπn, and a folic acid derivative

38 A method of prepaπng a pharmaceutical composition useful for treating tumors or tumor metastases in a patient, comprising combining an anti-cancer agent with an IGFR inhibitor of Formula I-

I or a pharmaceutically acceptable salt thereof, wherein. Xi and X ₂ are each independently N or -C-(E') _aa ; X ₅ is N, -C-(E') _aa , or -N-(E ¹ ) _* ,; X ₃ , X ₄ , Xe, and X ₇ are each independently N or C; wherein at least one of X ₃ , X ₄ , Xs, Xe, and X ₇ is independently N or -N-(E') _aa ; Q' is

X _n , X ₁₂ , X|3, Xi4, X)S, and X ₁₆ are each independently N, -C-(E ¹ ') _bb , or -N ⁺ -O ; wherein at least one of X _{) (} , X12, Xi ₃ , Xj ₄ , Xιs, and X, ₆ is N or -N ⁺ -O ^" ;

R ¹ is absent, Q-ioalkyl, bicycloCs.ioalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, heterobicycloCs.i ₀ alkyl, spiroalkyl, or heterospiroalkyl, any of which is optionally substituted by one or more independent G" substituents;

E ¹ , E", G ¹ , and G ⁴¹ are each independently halo, -CF ₃ , -OCF ₃ , -OR ² , -NR ² R ³ (R ^2a )j,, -C(=O)R ² , -CO ₂ R ² , -CONR ² R ³ , -NO ₂ , -CN, -S(O) _j ,R ² , -SO ₂ NR ² R ³ , -NR ² C(O)R ³ , -NR ² C(=O)OR ³ , -NR ² C(=O)NR ³ R ² \ -NR ² S(O) _J1 R ³ , -C(=S)OR ² , -C(=O)SR ² , -NR ² C(=NR ³ )NR ^2a R ^3a , -NR ² C(=NR ³ )OR ^2a , -NR ² C(=NR ³ )SR ^2a , -OC(=O)OR ² , -OC(=O)NR ² R ³ , -OC(=O)SR ² , -SC(=O)OR ² , -SC(=O)NR ² R ³ , Co-ioalkyl, C _2-10 alkenyl, C ₂ ., ₀ alkynyl, C.^alkoxyC _M oalkyl, C,,,oalkoxyC _2- ioalkenyl, C _1- ioalkoxyC ₂ _ioalkynyl, Ci. _t oalkylthioCi.ioalkyl, C _M oalkylthioC ₂ -ioalkenyl, Ci.ioalkylthioC ₂ . ₁₀ alkynyl, cycloC _3-8 alkyl, cycloC ₃ . ₈ alkenyl, CyCIoC _3-S aIlCyIC ₁ . i _O alkyl, cycloC ₃ . ₈ alkenylC|.| ₀ alkyl, cycloC _3-8 alkylC _{2- l} oalkenyl, cycloC _3-8 alkenylC2-ιoalkenyl, cycloC ₃ . ₈ alkylC ₂ .ioalkynyl, cycloC _3-8 alkenylC ₂ -i ₀ alkynyl, heterocyclyl-Co-ioalkyl, heterocyclyl-C _2-l0 alkenyl, or heterocyclyl-C ₂ . ₁₀ alkynyl, any of which is optionally substituted with one or more independent halo, oxo, -CF ₃ , -OCF ₃ , -OR ²²² , -NR ²²² R ³³³ (R ^222a ) _j i _a , -C(=O)R ²²² , -CO ₂ R ²²² , -C(=O)NR ²²² R ³³³ , -NO ₂ , -CN, -S(O) _Jla R ²²² , -SO ₂ NR ²²² R ³³³ , -NR ²²² CO=O)R ³³³ , -NR ²²² C(=O)OR ³³³ , -NR ²²² C(=O)NR ³³³ R ^222a , -NR ²²² S(O) _{J la} R ³³³ , -C(=S)OR ²²² , -C(=O)SR ²²² , -NR ²²² C(=NR ³³³ )NR ^222a R ^333a , -NR ²²² C(=NR ³³³ )OR ^222a , -NR ²²² C(=NR ³³³ )SR ^222a , -OC(=O)OR ²²² , -OC(=O)NR ²²² R ³³³ , -OC(=O)SR ²²² , -SC(=O)OR ²²² , or -SC(=O)NR ²²² R ³³³ substituents; or E ¹ , E", or G ¹ optionally is -(W) _n -(Y ¹ ),^ ⁴ ; or E ¹ , E", G ¹ , or G ⁴¹ optionally independently is aryl-Co-ioalkyl, aryl— C _2- | _O alkenyl, aryl-C _{2- 10} alkynyl, hetaryl-C _o- ioalkyl, hetaryl-C _2-10 alkenyl, or hetaryl-C ₂ -ioalkynyl, any of which is optionally substituted with one or more independent halo, -CF ₃ , -OCF ₃ , -OR ²²² , -NR ²²² R ³³³ (R ^222a ) _j2a , -C(O)R ²²² , -CO ₂ R ²²² , -C(=O)NR ²²² R ³³³ , -NO ₂ , -CN, -S(O) _j2a R ²²² , -SO ₂ NR ²²² R ³³³ , -NR ²²² C(=O)R ³³³ , -NR ²²² C(=O)OR ³³³ , -NR ²²² C(O)NR ³³³ R ^222a , -NR ²²² S(O) _j2a R ³³³ , -C(=S)OR ²²² , -C(O)SR ²²² , -NR ²²² C(=NR ³³³ )NR ^222a R ^333a , -NR ²²² C(=NR ³³³ )OR ^222a , -NR ²²² C(=NR ³³³ )SR ^222a , -OC(=O)OR ²²² , -OC(=O)NR ²²² R ³³³ , -OC(=O)SR ²²² , -SC(=O)OR ²²² , or -SC(O)NR ²²² R ³³³ substituents;

G" is halo, oxo, -CF ₃ , -OCF ₃ , -OR ²¹ , -NR ²¹ R ^3l (R ^2al ) _j4 , -C(O)R ²¹ , -CO ₂ R ²¹ , -C(O)NR ²¹ R ³¹ , -NO ₂ , -CN, -S(O) _j4 R ²¹ , -SO ₂ NR ²¹ R ³¹ , NR ²¹ (C=O)R ³¹ , NR ²¹ C(=O)OR ³¹ , NR ² ' C(O)NR ³¹ R ²³ ', NR ²¹ S(O) _J4 R ³¹ , -C(=S)OR ²¹ , -C(=O)SR ²¹ , -NR ²¹ C(=NR ³¹ )NR ^2aI R ^3al , -NR ²¹ C(=NR ^3l )OR ^2al , -NR ^2l C(=NR ³¹ )SR ^2al , -OC(O)OR ²¹ , -OC(O)NR ²¹ R ³¹ , -OC(=O)SR ²¹ , -SC(O)OR ²¹ , -SC(O)NR ²¹ R ³¹ , -P(O)OR ²¹ OR ³¹ , C _1-10 alkylidene, Co. ₁₀ alkyl, C _2-I0 alkenyl, C _2-10 alkynyl, C,.,oalkoxyC,. loalkyl, C _MO alkoxyC ₂ .ioalkenyl, Ci. ₁₀ alkoxyC _2- , ₀ alkynyl, d.ioalkylthioQ. ₁₀ alkenyl, C _M0 alkylthioC _2-10 alkynyl, cycloC _3-8 alkyl, cycloC _3-8 alkenyl, cycloC ₃ . ₈ alkylCi.ioalkyl, cycloC ₃ . galkenylCi.ioalkyl, cycloC _3-8 alkylC ₂ ., ₀ alkenyl, cycloC _3-8 alkenylC _2- ioalkenyl, cycloC _3-8 alkylC ₂ .i ₀ alkynyl, cycloC ₃ . ₈ alkenylC _2-10 alkynyl, heterocyclyl-Cnoalkyl, heterocyclyl-C ₂ . ₁₀ alkenyl, or heterocyclyl-C ₂ . _l oalkynyl, any of which is optionally substituted with one or more independent halo, oxo, -CF ₃ , -OCF ₃ ,

-OR ²²²¹ , -NR ²²²¹ R ³³³¹ (R ^222a V, -C(O)R ²²²¹ , -CO ₂ R ²²²¹ , -C(=O)NR ²²²¹ R ³³³ \ -NO ₂ , -CN, -S(O)^R ²²²¹ , -SO ₂ NR ²²²¹ R ³³³¹ , -NR ²²²¹ CC=O)R ³³³¹ , -NR ^222I C(=O)OR ³³³¹ , -NR ²²²¹ C(=O)NR ³³³¹ R ^222al , -NR ²²²¹ S(O) _j4a R ³³³¹ , -C(=S)OR ²²²¹ , -CC=O)SR ²²²¹ , -NR ²²²¹ CC=NR ³³³¹ )NR ^222aI R ^333al , -NR ²²²¹ C(=NR ^333l )OR ^222al , -NR ²²²¹ CC=NR ³³³¹ )SR ^222al , -OC(=O)OR ²²²¹ , -OC(=O)NR ²²²¹ R ³³³¹ , -OCC=O)SR ²²²¹ , -SCC=O)OR ²²²¹ , -P(O)OR ²²²¹ OR ³³³¹ , or -SCC=O)NR ²²²¹ R ³³³¹ substituents; or G" is aryl-Co-i _O alkyl, aryl-C _2- ioalkenyl, aryl-C ₂ . ₁₀ alkynyl, hetaryl-Cc _M oalkyl, hetaryl-C ₂ . _l oalkenyl, or hetaryl-C _2- ioalkynyl, any of which is optionally substituted with one or more independent halo, -CF ₃ , -OCF ₃ , -OR ²²²¹ , -NR ²²²¹ R ³³³¹ CR ^222al ) _j5a , -C(O)R ²²²¹ , -CO ₂ R ²²²¹ , -C(=O)NR ^222I R ³³³¹ , -NO ₂ , -CN, -SCO) _j5a R ²²²¹ , -SO ₂ NR ²²²¹ R ³³³¹ , -NR ²²²¹ CC=O)R ³³³¹ , -NR ²²²¹ C(=O)OR ³³³¹ , -NR ²²²¹ CC=O)NR ³³³¹ R ²²² " ¹ , -NR ²²²¹ SCO) _j5 aR ³³³¹ , -C(=S)OR ²²²¹ , -CC=O)SR ²²²¹ , -NR ²²²¹ C(=NR ³³³¹ )NR ^222al R ^333al _J -NR ²²²¹ CC=NR ³³³¹ )OR ^222al , -NR ²²²¹ CC=NR ³³³¹ )SR ^222aI , -OCC=O)OR ²²²¹ , -OCC=O)NR ²²²¹ R ³³³¹ , -OC(=O)SR ²²²¹ , -SCC=O)OR ²²²¹ , -PCO)OR ²²²¹ OR ³³³¹ , or -SCC=O)NR ²²²¹ R ³³³¹ substituents; or G ^{1 1} is C, taken together with the carbon to which it is attached forms a C=C double bond which is substituted with R ⁵ and G ^{1 1 1} ;

R ² , R ^2a , R ³ , R ^3a , R ²²² , R ^222a , R ³³³ , R ^333a , R ²¹ , R ^2al , R ³¹ , R ^3al , R ²²²¹ , R ^222a \ R ³³³¹ , and R ^333al are each independently Co.| ₀ alkyl, C _2- ιoalkenyl, C _2- ioalkynyl, Ci.ioalkoxyCi.ioalkyl, Ci.ioalkoxyC _2- ioalkenyl, Ci- ιoalkoxyC ₂ .i ₀ alkynyl, Ci.ioalkylthioCi.ioalkyl, C _M oalkylthioC ₂ .ioalkynyl, cycloC _3-8 alkyl, cycloC ₃ _ ₈ alkenyl, cycloC _3-8 alkylC|.| ₀ alkyl, cycloC _3-8 alkenylCi.ioalkyl, cycloC ₃ . ₈ alkylC ₂ . loalkenyl, cycloC ₃ . ₈ alkenylC _2- ιoalkenyl, cycloC _3-8 alkylC ₂ .| _O alkynyl, cycloC ₃ . ₈ alkenylC _2- i ₀ alkynyl, heterocyclyl-Co-ioalkyl, heterocyclyl-C ₂ -ioalkenyl, heterocyclyl-C _2- i ₀ alkynyl, aryl-C _o .ioalkyl, aryl-C ₂ . loalkenyl, aryl-C ₂ .ιoalkynyl, hetaryl— Co-ioalkyl, hetaryl-C _2- ioalkenyl, or hetaryl— C _2- i _O alkynyl, any of which is optionally substituted by one or more independent G ¹¹¹ substituents; or in the case of -NR ² R ³ CR ² ");, or -NR ²²² R ³³³ (R ^222a ) _jla or -NR ²²² R ³³³ (R ^222a ) _j2a or -NR ²¹ R ³¹ (R ^2al ) _j4 or -NR ²²²¹ R ³³³¹ CR ²²²³ V or -NR ^222I R ³³³¹ (R ^222al ) _j5a , then R ² and R ³ , or R ²²² and R ³³³ , or R ²²²¹ and R ³³³¹ , respectfully, are optionally taken together with the nitrogen atom to which they are attached to form a 3- 10 membered saturated or unsaturated ring, wherein said ring is optionally substituted by one or more independent G ^{1 1} " substituents and wherein said ring optionally includes one or more heteroatoms other than the nitrogen to which R ² and R ³ , or R ²²² and R ³³³ , or R ²²²¹ and R ³³³¹ are attached;

W ¹ and Y' are each independently -O-, -NR ⁷ -, -S(O)J ₇ -, -CR ⁵ R ⁶ -, -N(C(O)OR ⁷ )-, -N(C(O)R ⁷ )-, -N(SO ₂ R ⁷ )-, -CH ₂ O-, -CH ₂ S-, -CH ₂ N(R ⁷ )-, -CHCNR ⁷ )-, -CH ₂ N(C(O)R ⁷ )-, -CH ₂ N(C(O)OR ⁷ )-, -CH ₂ N(SO ₂ R ⁷ )-, -CHCNHR ⁷ )-, -CHCNHC(O)R ⁷ )-, -CHCNHSO ₂ R ⁷ )-, -CHCNHCCO)OR ⁷ )-, -CHCOC(O)R ⁷ )-, -CH(OC(O)NHR ⁷ )-, -CH=CH-, -C≡C- -C(=NOR ⁷ )-, -C(O)-, -CH(OR ⁷ )-, -C(O)N(R ⁷ )-, -N(R ⁷ )C(O)-, -N(R ⁷ )S(O)-, -N(R ⁷ )S(O) ₂ - -OC(O)NCR ⁷ )-, -NCR^CCO)NCR ⁸ )-, -NR ⁷ CCO)O-, -S(O)NCR ⁷ )-, -SCO) ₂ N(R ⁷ )-, -N(C(O)R ⁷ )S(O)-, -NCCCO)R ⁷ )SCO) ₂ -, -NCR ⁷ )SCO)NCR ⁸ )-, -NCR ⁷ )S(O) ₂ NCR ⁸ )-, -CCO)N(R ⁷ )C(O)-, -S(O)NCR ⁷ )CCO)-,

-S(O) ₂ N(R ⁷ )C(O)-, -OS(O)N(R ⁷ )-, -OS(O) ₂ N(R ⁷ )- -N(R ⁷ )S(O)O-, -N(R ⁷ )S(O) ₂ O-, -N(R ⁷ )S(O)C(O)-, -N(R ⁷ )S(O) ₂ C(O)-, -SON(C(O)R ⁷ )-, -SO ₂ N(C(O)R ⁷ )-, -N(R ⁷ )SON(R ⁸ )-, -N(R ⁷ )SO ₂ N(R ⁸ )-. -C(O)O-, -N(R ⁷ )P(OR ⁸ )O-, -N(R ⁷ )P(OR ⁸ )-, -N(R ⁷ )P(O)(OR ⁸ )O-, -N(R ⁷ )P(O)(OR ⁸ )-, -N(C(O)R ⁷ )P(OR ⁸ )O-, -N(C(O)R ⁷ )P(OR ⁸ )-, -N(C(O)R ⁷ )P(O)(OR ⁸ )O-, -N(C(O)R ⁷ )P(OR ⁸ )- ₎ -CH(R ⁷ )S(O)-, -CH(R ⁷ )S(O) ₂ -, -CH(R ⁷ )N(C(O)OR ⁸ )-, -CH(R ⁷ )N(C(O)R ⁸ )-, -CH(R ⁷ )N(SO ₂ R ⁸ )-, -CH(R ⁷ )O-, -CH(R ⁷ )S-, -CH(R ⁷ )N(R ⁸ )-, -CH(R ⁷ )N(C(O)R ⁸ )-, -CH(R ⁷ )N(C(O)OR ⁸ )-, -CH(R ⁷ )N(SO ₂ R ⁸ )-, -CH(R ⁷ )C(=NOR ⁸ )-, -CH(R ⁷ )C(O)-, -CH(R ⁷ )CH(OR ⁸ )-, -CH(R ⁷ )C(O)N(R ⁸ )-, -CH(R ⁷ )N(R ⁸ )C(O)-, -CH(R ⁷ )N(R ⁸ )S(O)-, -CH(R ⁷ )N(R ⁸ )S(O) ₂ -, -CH(R ⁷ )OC(O)N(R ⁸ )-, -CH(R ⁷ )N(R ⁸ )C(O)N(R ^7a )-, -CH(R ⁷ )NR ⁸ C(O)O-, -CH(R ⁷ )S(O)N(R ⁸ )-, -CH(R ⁷ )S(O) ₂ N(R ⁸ )-, -CH(R ⁷ )N(C(O)R ⁸ )S(O)- _> -CH(R ⁷ )N(C(O)R ⁸ )S(O)-, -CH(R ⁷ )N(R ⁸ )S(O)N(R ^7a )-, -CH(R ⁷ )N(R ⁸ )S(O) ₂ N(R ^7a )-, -CH(R ⁷ )C(O)N(R ⁸ )C(O)-, -CH(R ⁷ )S(O)N(R ⁸ )C(O)-, -CH(R ⁷ )S(O) ₂ N(R ⁸ )C(O)-, -CH(R ⁷ )OS(O)N(R ⁸ )-, -CH(R ⁷ )OS(O) ₂ N(R ⁸ )-, -CH(R ⁷ )N(R ⁸ )S(O)O-, -CH(R ⁷ )N(R ⁸ )S(O) ₂ O-, -CH(R ⁷ )N(R ⁸ )S(O)C(O)-, -CH(R ⁷ )N(R ⁸ ) S (O) ₂ C(O)-, -CH(R ⁷ )SON(C(O)R ⁸ )-, -CH(R ⁷ )SO ₂ N(C(O)R ⁸ )-, -CH(R ⁷ )N(R ⁸ )SON(R ^7a )-, -CH(R ⁷ )N(R ⁸ )SO ₂ N(R ^7a )-. -CH(R ⁷ )C(O)O-, -CH(R ⁷ )N(R ⁸ )P(OR ^7a )O-, -CH(R ⁷ )N(R ⁸ )P(OR ^7a )-, -CH(R ⁷ )N(R ⁸ )P(0)(OR ^7a )O-, -CH(R ⁷ )N(R ⁸ )P(0)(0R ^7a )-, -CH(R ⁷ )N(C(O)R ⁸ )P(0R ^7a )0-, -CH(R ⁷ )N(C(O)R ⁸ )P(OR ^7a )-, -CH(R ⁷ )N(C(O)R ⁸ )P(O)(OR ^7a )O-, or -CH(R ⁷ )N(C(O)R ⁸ )P(OR ^7a )-;

R ⁵ , R ⁶ , G ¹ ", and G ¹ " ¹ are each independently Q-ioalkyl, C ₂ ,,oalkenyl, C ₂ . _l0 alkyτiyl, C _M oalkoxyCi.ioalkyl, Ci.| ₀ alkoxyC ₂ .ιoalkenyl, C _M0 alkoxyC ₂ .i ₀ alkynyl, Ci.ioalkylthioCi.ioalkyl, Ci. ₁₀ alkylthioC ₂ _ioalkenyl, C ₎ . ₁ oalkylthioC _2- | ₀ alkynyl, cycloC _3-8 alkyl, cycloC _3-8 alkenyl, cycloC ₃ . ₈ alkylC]. !oalkyl, cycloC ₃ . ₈ alkenylCi.ioalkyl, cycloC ₃ . ₈ alkylC ₂ -ioalkenyl, cycloC ₃ .galkenylC ₂ .ιoalkenyl, cycloC ₃ . ₈ alkylC _2-10 alkynyl, cycloC _3-8 alkenylC ₂ .ioalkynyl, heterocyclyl-Ccoalkyl, heterocyclyl-C^.oalkenyl, heterocyclyl-C _∑ .ioalkynyl, aryl-Co-ioalkyl, aryl-C _2- ioalkenyl, aryl-C ₂ . ₎₀ alkynyl, hetaryl-Co-i _O alkyl, hetaryl— C _2- ιoalkenyl, or hetaryl-C _2-10 alkynyl, any of which is optionally substituted with one or more independent halo, -CF ₃ , -OCF ₃ , -OR ⁷⁷ , -NR ⁷⁷ R ⁸⁷ , -C(O)R ⁷⁷ , -CO ₂ R ⁷⁷ , -CONR ⁷⁷ R ⁸⁷ , -NO ₂ , -CN, -S(O) _j5a R ⁷⁷ , -SO ₂ NR ⁷⁷ R ⁸⁷ , -NR ⁷⁷ C(=O)R ⁸⁷ , -NR ⁷⁷ C(=O)OR ⁸⁷ , -NR ⁷⁷ C(=O)NR ⁷⁸ R ⁸⁷ , -NR ⁷⁷ S(O) _j5a R ⁸⁷ , -C(=S)OR ⁷⁷ , -C(=O)SR ⁷⁷ , -NR ⁷⁷ C(=NR ⁸⁷ )NR ⁷⁸ R ⁸⁸ , -NR ⁷⁷ C(=NR ⁸⁷ )OR ⁷⁸ , -NR ⁷⁷ C(=NR ⁸⁷ )SR ⁷⁸ , -OC(=O)OR ⁷⁷ , -OC(=O)NR ⁷⁷ R ⁸⁷ , -OC(=O)SR ⁷⁷ , -SC(=O)OR ⁷⁷ , -P(O)OR ⁷⁷ OR ⁸⁷ , or -SC(=O)NR ⁷⁷ R ⁸⁷ substituents; or R ⁵ with R ⁶ are optionally taken together with the carbon atom to which they are attached to form a 3-10 membered saturated or unsaturated ring, wherein said ring is optionally substituted with one or more independent R ⁶⁹ substituents and wherein said ring optionally includes one or more heteroatoms;

R ⁷ , R ^7a , and R ⁸ are each independently acyl, Co-ioalkyl, C ₂ -κ>alkenyl, aryl, heteroaryl, heterocyclyl or cycloC _3- i ₀ alkyl, any of which is optionally substituted by one or more independent G ¹ " substituents;

R ⁴ is Co-ioalkyl, C _2- i _O alkenyl, C _2- ioalkynyl, aryl, heteroaryl, cycloCs-ioalkyl, heterocyclyl, cycloC ₃ . galkenyl, or heterocycloalkenyl, any of which is optionally substituted by one or more independent G ⁴¹ substituents;

R ⁶⁹ is halo, -OR ⁷⁸ , -SH, -NR ⁷⁸ R ⁸⁸ , -CO ₂ R ⁷⁸ , -C(=O)NR ⁷⁸ R ⁸⁸ , -NO ₂ , -CN, -S(O) _j8 R ⁷⁸ , -SO ₂ NR ⁷⁸ R ⁸⁸ , Co-ioalkyl, C ₂ .i _O alkenyl, C ₂ . ₁₀ alkynyl, Ci.ioalkoxyQ.ioalkyl, Ci. ₁₀ alkoxyC _2- ioalkenyl, C ₁ . ₁₀ alkoxyC ₂ -ιoalkynyl, CnoalkylthioCi-ioalkyl, C _l- i ₀ alkylthioC _2- ioalkenyl, CioalkylthioCz-ioalkynyl, cycloC ₃ . ₈ alkyl, cycloC _3-8 alkenyl, cycloC ₃ . ₈ alkylCi. _l0 alkyl, cycloC ₃ . ₈ alkenylCi.ioalkyl, cycloC ₃ . ₈ alkylC ₂ . _l oalkenyl, cycloC ₃ . ₈ alkenylC _2-l oalkenyl, cycloC _3-8 alkylC _2- ioalkynyl, cycloC _3-8 alkenylC _2- ιoalkynyl, heterocyclyl-Co-ioalkyl, heterocyclyl-C _2- i ₀ alkenyl, or heterocyclyl-C ₂ .ioalkynyl, any of which is optionally substituted with one or more independent halo, cyano, nitro, -OR ⁷⁷⁸ , -SO ₂ NR ⁷⁷⁸ R ⁸⁸⁸ , or -NR ⁷⁷⁸ R ⁸⁸⁸ substituents; or R ⁶⁹ is aryl-C _o -i _o alkyl, aryl-C _2- ιoalkenyl, aryl-C ₂ .ioalkynyl, hetaryl-Co-ioalkyl, hetaryl-C ₂ . _l oalkenyl, hetaryl-C ₂ .ιoalkynyl, monoCaryOaminoCi-βalkyl, di(aryl)aminoC| _-6 alkyl, or any of which is optionally substituted with one or more independent halo, cyano, nitro, -OR ⁷⁷⁸ , Cj.ioalkyl, C ₂ .ioalkenyl, C _2- ι ₀ alkynyl, haloC _1-10 alkyl, haloC ₂ .i _O alkenyl, haloC ₂ .| ₀ alkynyl, — COOH, -C(=O)NR ⁷⁷⁸ R ⁸⁸⁸ , -SO ₂ NR ⁷⁷⁸ R ⁸⁸⁸ , or -NR ⁷⁷⁸ R ⁸⁸⁸ substituents; or in the case Of-NR ⁷⁸ R ⁸⁸ , R ⁷⁸ and R ⁸⁸ are optionally taken together with the nitrogen atom to which they are attached to form a 3-10 membered saturated or unsaturated ring, wherein said ring is optionally substituted with one or more independent halo, cyano, hydroxy, nitro, Ci_i ₀ alkoxy, -SO ₂ NR ⁷⁷⁸ R ⁸⁸⁸ , or -NR ⁷⁷⁸ R ⁸⁸⁸ substituents, and wherein said ring optionally includes one or more heteroatoms other than the nitrogen to which R ⁷⁸ and R ⁸⁸ are attached;

R ⁷⁷ , R ⁷⁸ , R ⁸⁷ , R ⁸⁸ , R ⁷⁷⁸ , and R ⁸⁸⁸ are each independently Ccoalkyl, C ₂ . ₁₀ alkenyl, C ₂ . ₁₀ alkynyl, C _{1- l} oalkoxyCi-ioalkyl, C _M oalkoxyC ₂ . ₁₀ alkenyl, Ci.ioalkoxyC _2- ioalkynyl, Q.njalkylthioCi.ioalkyl, Ci- ioalkylthioC ₂ .ioalkenyl, C _M oalkylthioC _2- ioalkyny], cycloC _3-8 alkyl, cycloC ₃ . ₈ alkenyl, cycloC _3-8 aIkylC,. _l oalkyl, cycloC ₃ . ₈ alkenylC|.ιoalkyl, cycloC ₃ . ₈ alkylC ₂ .ioalkenyl, cycloC ₃ . ₈ alkenylC ₂ .ιoalkenyl, cycloQj. ₈ alkylC ₂ .| _O alkynyl, cycloC _3-8 alkenylC2-ioalkynyl, heterocyclyl-Co-ioalkyl, heterocyclyl-C ₂ .| ₀ alkynyl, Cuoalkylcarbonyl, C ₂ .| ₀ alkenylcarbonyl, C _2- i ₀ alkynylcarbonyl, C _{1- )0} alkoxycarbonyl, Ci.ioalkoxycarbonylCi.joalkyl, diC]. _fi alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl, or

Ci.i ₀ alkyl(aryl)aminocarbonyl, any of which is optionally substituted with one or more independent halo, cyano, hydroxy, nitro, Ci _-10 alkoxy, -S0 ₂ N(Co- ₄ alkyl)(Co- ₄ alkyl), or substituents; or R ⁷⁷ , R ⁷⁸ , R ⁸⁷ , R ⁸⁸ , R ⁷⁷⁸ , and R ⁸⁸⁸ are each independently aryl-Q-ioalkyl, aryl-C ₂ .i ₀ alkenyl ₅ aryl-C _2- i _O alkynyl, hetaryl-C _o .ioalkyl, hetaryl-C _2-) oalkenyl, hetaryl-C ₂ .ioalkynyl, mono(C _1-6 alkyl)aminoC,. ₆ alkyl, di(Ci.6alkyl)aminoCi _-6 alkyl, mono(aryl)aminoCi. ₆ alkyl, di(aryl)aminoCi. ₆ alkyl, or -N(C|^alkyl)-C|^alkyl-aryl, any of which is optionally substituted with one or more independent halo, cyano, nitro, -O(C( _M alkyl), Q.^alkyl, C _2-10 alkenyl, C ₂ . ₎₀ alkynyl, haloCuioalkyl,

haloC ₂ .| ₀ alkenyl, haloC ₂ -ioalkynyl, -COOH, -S0 ₂ N(Co _-4 a]kyl)(C _(M alkyl), or -N(Co-4alkyl)(Co- ₄ alkyl) substituents; n, m,j l , j la,j2a, j4, j4a, j5a, j7, andjδ are each independently O, I, or 2; and aa and bb are each independently 0 or 1.

39. A method of preparing a pharmaceutical composition useful for treating tumors or tumor metastases in a patient, comprising combining an anti-cancer agent with an IGFR inhibitor selected from the group consisting of:

3-Cyclobutyl-l-(2-pyridin-2-ylqumolin-7-yl)-imidazo[l,5-α]pyrazin-8-ylarnine; 3-Cyclobutyl-l -(2 -thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine; 3-Cyclobutyl-l -(2-phenoxyquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-8-ylamine; [7-Cδ-Amino-S-cyclobutylimidazotl.S-aJpyrazin-l-y^-quinolin-Z-y^-phenylamine; 1 -(ό-Chloro^-phenylquinolin^-ytyO-cyclobutylimidazof 1 ,5-a]pyrazin-8-ylamine; 1 -(β-Chloro^-pyridin^-ylquinolin^-yO-S-cyclobutylimidazof 1 ,5-a]pyrazin-8-ylamine; l-(6-Chloro-2-thiophen-2-ylquinolin-7-yl)-3-cyclobutylimidazo[l,5-a]pyrazin-8-ylamine; 1 -(6-Chloro-2-phenoxyquinolin-7-yl)-3-cyclobutylimidazo[ 1 ,5-a]pyrazin-8-ylamine; [7-(8-Amino-3-cyclobutylimidazo[ 1 ,5-a]pyrazin- 1 -yl)-6-chloroquinolin-2-yl]-phenyl -amine; 3-Cyclobutyl-l-(8-fluoro-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine; 3-Cyclobutyl-l -(8-fluoro-2-pyridin-2-y1quinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-8-ylamine; 3-Cyclobutyl-l -(8-fluoro-2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine; 3-Cyclobutyl-l -(8-fluoro-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine; [7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l-yl)-8-fiuoroquinolin-2-yl]-phenyl-amine; 3-Cyclobutyl-l -(4-methyl-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine; 3-Cyclobutyl-l -(4-methyl-2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine; 3-Cyclobutyl-l -(4-methyl-2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine; [7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l-yl)-4-methylquinolin-2-yl]-phenylamine; 3-Cyclobutyl-l-(4-methyl-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine; [7-(8-Amino-3-cyclobuty]imidazo[l,5-a]pyrazin-l-yl)-2-phenylquinolin-4-yl]-methylamine; [7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l-yl)-2-pyridin-2-ylquinolin-4-yl]-methylamine; [7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l-yl)-2-thiophen-2-ylquinolin-4-yl]-methylamine; [7-(8-Amino-3-cyclobutylimidazo[l,5-a]pyrazin-l-yl)-2-phenoxyquinolin-4-yl]-methylamine; 7-(8-Amino-3-cyclobutylimidazo[ 1 ,5-α]pyrazin-l -y^-V-methyl-λ^-phenylquinoline^^-diamine; S-fδ-Amino-l^-pyridin-2-ylquinolin^-ylJ-imidazof l.S-alpyrazin-S-yll-cyclobutanol; 3-[8-Amino-l-(2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol; 3-[8-Amino-l-(2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol; 3-[8-Amino-l -(2-phenylaminoquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-3-yl]-cyclobutanol; 3-[8-Amino-l-(6-chloro-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol; 3-[8-Amino-l-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

S-fδ-Amino-lKό-chloro-Z-thiophen-Z-ylquinolin-7-yO-irnidazotl.S-alpyrazin-S-ylJ-cyclobutanol;

3 -[8- Amino- 1 -(6-chloro-2 -pheny laminoquinolin-7-yl)-imidazo [1,5 -a]pyrazin-3 -yl] -cyclobutanol ;

3-[8-Amino-l-(6-chloro-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

S-fS-Amino-l-CS-fluoro-I-pyridin-2-ylquinolin-7-yO-iπiidazotl.S^pyrazin-S-ylJ-cyclobutanol;

S-tS-Amino-l-Cδ-fluoro^-thiophen-Z-ylqυinolin-y-y^-imidazotl^^pyrazin^-ylJ-cyclobutanol;

3-[8-Amino-l-(8-fluoro-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyτazin-3-yl]-cyclobutanol;

S-tδ-Amino-l-CS-fluoro-Z-phenylaminoquinolin-7-yO-imidazotl.S-ajpyrazin-S-y^-cyclobutanol;

3-[8-Amino-l-(8-fluoro-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(8-fluoro-4-methyl-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-[8-Amino-l-(8-fluoro-4-methyl-2-thiophen-2-yl-quinolin-7-yl)-imidazo[l ,5-a]pyrazin-3-yl]- cyclobutanol;

3-[8-Amino-l-(8-fluoro-4-methyl-2-pyridin-2»ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclobutanol;

3-[8-Amino-l-(8-fluoro-4-methyl-2-phenylaminoquinolin-7-yl)-imidazo[l _> 5-a]pyτazin-3-yl]- cyclobutanol;

3-[8-Amino-l-(8-fluoro-4-methyl-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclobutanol;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

S-CS-Azetidin-l-ylmethylcyclobuty^-l^-thiophen-2-ylquinolin^-y^-imidazoEUS^pyrazin-S-ylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l -(2-phenoxyquinolin-7-yl)-imidazo[l ,5-a]pyrazin-8-ylaπiine;

{7- [ 8- Amino-3 -(3 -azetidin- 1 -ylmethylcyclobutyl)-imidazo [ 1 ,5 -a]pyrazin - 1 -yl] -quinol in-2 -yl } - phenylamine;

S-fS-Azetidin-l-ylmethylcyclobuty^-l^δ-chloro^-phenylquinolin^-y^-imidazotljS-ajpyrazin-S- yl amine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(6-chloro-2-pyridin-2-yl-quinolin-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(6-chloro-2-thiophen-2-yl-quinolin-7-yl)-imidazo[l,5-a]pyrazin-

8-ylamine;

{7-[8-Amino-3 -(3 -azetidin- 1 -ylmethylcyclobutyl)-imidazo [ 1 ,5-a]pyrazin- 1 -yl] -6-chloro-quinolin-2-yl } - phenylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(6-chloro-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

S-CS-Azetidin-l-ylmethylcyclobuty^-l^-methyl^-phenylquinolin^-yO-imidazof l.S-aJpyrazin-S- ylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-jmidazo[l,5-a]pyrazin-8- ylamine;

S-CS-Azetidin-l-ylmethylcyclobutyO-i^-methyl^-thiophen-2-ylquinolin^-yO-imidazofl.S-aJpyrazin-

8-ylamine;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(4-methyl-2-phenoxyqυinolin-7-yl)-imidazo[l ,5-a]pyrazin-8- ylamme;

{y-tS-Amino-S-CS-azetidin-l-ylmethylcyclobuty^-imidazofl _j S-ajpyrazin-l-ylJ^-methyl-quinohn-Z-yl}- phenyl-amine;

3-(3-Dimethylaminomethylcyclobutyl)-l-(2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine,

3-(3-Dimethylaminomethylcyclobutyl)-l-(2-thiophen-2-ylquinohn-7-yl)-imidazo[l,5-a]pyraztn-8- ylamine;

{y-tS-Ammo-S-CS-dimethylammomethylcyclobutyO-imidazofl.S-aJpyrazin-l-yll-quinolin-2-yl}- phenylamine,

S^-Dimethylaminomethylcyclobuty^-l^-phenoxyquinolin-V-yO-imidazofl _j S-aJpyrazin-S-ylamine, l^ό-Chloro^-phenylquinolin-V-yO-S^-dimethylaminomethylcyclobuty^-imidazofl.S-ajpyrazin-δ- ylamine, l-(6-Chloro-2-pyπdin-2-ylquinohn-7-yl)-3-(3-dimethylaminomethylcycIobutyl)-imidazo[l,5-a]pyrazin-

8-ylamine, l-(6-Chloro-2-thiophen-2-ylquinohn-7-yl)-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l,5-a]pyrazin-

8-ylamine; l-(6-Chloro-2-phenoxyquinolin-7-yl)-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l,5-a]pyrazm-8- ylamine;

{7-[8-Amino-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l,5-a]pyrazin-l-yl]-6-chloroquinolin-2-yl}- phenylamine;

3-(3-Dimethylaminomethylcyclobutyl)-l-(4-methyl-2-phenylquinohn-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine,

3-(3-Dimethylaminomethylcyclobutyl)-l-{4-methyl-2-pyπdin-2-ylquinohn-7-yl)-imidazo[l ,5-a]pyrazin-

8-ylamme,

3-(3-Dimethylaminomethylcyclobutyl)-l-(4-methyl-2-thiophen-2-ylqumolin-7-yl)-ιmidazo[l,5- a]pyrazin-8-ylamine,

{7-[8-Amino-3-(3-dimethylaminomethylcyclobutyl)-imidazo[l,5-a]pyrazm-l-yl]-4-methylquinohn-2- yl } -phenylamine ;

S-CS-Dimethylaminomethylcyclobutyli-l^-methyl^-phenoxyquinolin^-yO-imidazof l.S-ajpyrazin-S- ylamine;

4-[8-Ammo-l-(2-pyπdin-2-ylquinohn-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(2-thiophen-2-ylquinohn-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide,

4-[8-Amino-l -(2-phenoxyquinohn-7-yl)-imidazo[l ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(2-phenylaminoquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l -(6-chloro-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l -(6-chloro-2-pyridin-2-ylquinolin-7-yl)-imidazo[l ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l -(6-chloro-2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclohexanecarboxylic acid amide;

4-[8-Amino-] -(6-chloro-2-phenylaminoquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclohexanecarboxylic acid amide;

4-[8-Amino-l -(6-chloro-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l -(4-methyl-2-phenylquinolin-7-yl)-imidazo[l ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l -(4-methyl-2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(4-methyl-2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l -(4-methyl-2-phenylaminoquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]- cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-y]]-cyclohexanecarboxylic acid methylamide;

4-[8-Amino-l -(2-thiophen-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylamide;

4-[8-Amino-l -(2-phenylaminoquinolin-7-yl)-imidazo[l ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylamide;

4-[8-Amino-l -(2-phenoxyquinolin-7-yl)-imidazo[l ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylamide;

3-(4-Aminomethylcyclohexyl)-l-(2-pyridin-2-ylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

S^-AminomethylcyclohexylJ-l^-thiophen-2-ylquinolin^-y^-imidazofljS-aJpyrazin-δ-ylamine;

3-(4-AminomethylcyclohexyI)-l-(2-phenoxyquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

{7-[8-Amino-3-(4-aminomethylcyclohexyl)-imidazo[l,5-a]pyrazin-l-yl]-quinolin-2-yl}-phenylamine;

7-Cyclobutyl-5-(2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-Cyclobutyl-5-(2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-Cyclobutyl-5-(2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

[7-(4-Amino-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-quinolin-2-yl]-phenylamine;

7-Cyclobutyl-5-(2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

5-(6-Chloro-2-phenylquinolin-7-yl)-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

5-(6-Chloro-2-pyridin-2-ylquinolin-7-yl)-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

5-(6-Chloro-2-thiophen-2-ylquinolin-7-yl)-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

5-(6-Chloro-2-phenoxyquinolin-7-yl)-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

[7-(4-Amino-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-6-chloroquinolin-2-yl]-phenylamine;

3.[4-Amino-5-(2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(2-pyridin-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobυtanol;

3-[4-Amino-5-(2-phenylaminoquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(2-phenoxyquinolin-7-yl)-pyπ"olo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(6-chloro-2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(6-chloro-2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(6-chloro-2-phenylaminoquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(8-fluoro-2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(8-fluoro-2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol; 3-[4-Amino-S^S-fluoro^-pyridin-2-ylquinolin-7-yl)-pyrrolo^^-dJpyrimidin^-ylJ-cyclobutanol;

3-[4-Amino-5-(8-fluoro-2-phenylaminoquinolin-7-yl)-pyrτolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

3-[4-Amino-5-(8-fluoro-2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanol;

7-Cyclobutyl-5-(8-fluoro-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-Cyclobutyl-5-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-7H-pyrτolo[2,3-d]pyrimidin-4-ylamine;

7-Cyclobutyl-5-(8-fluoro-2-thiophen-2-yl-quinoliτi-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-Cyclobutyl-5-(8-fluoro-2-phenoxyquinolin-7-yl)-7H-pyπOlo[2,3-d]pyrimidin-4-ylamine;

[7-(4-Amino-7-cyclobutyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-8-fluoroquinolin-2-yl]-phenylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-phenylquinolin-7-yl)-7H-ρyrrolo[2,3-d]pyrimidin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-thiophen-2-yl-quinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-quinolin-2-yl}- phenylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(6-chloro-2-phenylquinoliπ-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(6-chloro-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyπmidin-

4-ylamine,

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrinndin-5-yl]-6-chloroquinohn-2- yl}-phenylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(8-fluoro-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidm-4- ylamine;

7-(3 -Azetidin- 1 -ylmethylcyclobutyl)-5 -(8-fluoro-2-pyridin-2-ylquinohn-7-yl)-7H-pyrrolo[2, 3 - d]pyrimidin-4-ylamine,

7-(3-Azetidm-l-ylmethylcyclobutyl)-5-(8-fluoro-2-thiophen-2-ylquinohn-7-yl)-7H-pyrrolo[2,3- d]pyrimιdin-4-ylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-8-fluoroquinolin-2- yl } -phenyl -amine;

7-(3-Azetidm-l-ylmethylcyclobutyl)-5-(8-fluoro-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-

4-ylamme,

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(4-methyl-2-pyπdin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyπmidin-4-ylamine ,

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-{4-methyl-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyπmidin-4- ylamine,

7-(3-Azetidm-l-ylmethylcyclobutyl)-5-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pynmidin-4-ylamine,

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(4-methyl-2-phenoxyquinohn-7-yl)-7H-pyrrolo[2,3-d]pyπmidin-

4-ylamine,

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyπmidin-5-yl]-4-methy]quinolin-2- yl } -phenylamine,

{7-[4-Ammo-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidm-5-yl]-2-phenylquinohn-4- yl} -methylamine,

{7-[4-Amino-7-(3 -azetidin- l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyπmidin-5-yl]-2-pyπdin-2- ylquinohn-4-yl } -methylamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-thiophen-2- ylquinohn-4-yl } -methylamine;

7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7H-pyrτolo[2,3-rf]pyπmidin-5-yl]-N ⁴ -methyl-N ² - phenylquinoline-2,4-diamine;

{7-[4-Amino-7-(3-azetidin-l-ylmethylcyclobutyl)-7η-pyrrolo[2,3-d]pyπmidin-5-yl]-2-phenoxyquinolin-

4-yl } -methylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-phenylquinohn-7-yl)-7H-pyrrolo[2,3-d]pyπmidin-4- ylamine,

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-pyπdin-2-ylqu]nohn-7-yl)-7H-pyπOlo[2,3-d]pyrimidin-4- ylamine,

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

T^S-Dimethylaminoiπethylcyclobuty^-5-(2-phenoxyquinolin-7-y^-TH-pyrrolofl^-dJpyrimidin^- ylamine;

{7-^-Amino-y-fS-dimethylaminomethylcyclobutyO-TH-pyrrolo^ _j S-dJpyrimidin-S-ylJ-quinolin-2-yl}- phenylamine;

5-(6-Chloro-2-phenylquinolin-7-yl)-7-(3-diπiethylaπiinomethylcyclobutyl)-7H-pyiτolo[2,3-d]ρyrimidin-

4-ylamine;

5-(6-Chloro-2-pyridin-2-ylquinolin-7-yl)-7-(3-dimethylaminomethylcyclobutyl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylaτnine;

5-(6-Chloro-2-thiophen-2-ylquinolin-7-yl)-7-(3-dimethylaminomethylcyclobutyl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

{7-[4-Amino-7-(3-dimethylaminomethylcyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-6-chloroquinolin-

2-yl } -phenylamine;

5-(6-Chloro-2-phenoxyquinolin-7-yl)-7-(3-dimethylaminomethylcyclobutyl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(8-fluoro-2-pyπdin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]ρyrimidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(8-fluoro-2-phenylquinolin-7-yl)-7H-pyiTolo[2,3-d]pyrimidin-

4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(8-fluoro-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(8-fluoro-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(4-methyl-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-

4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(4-methyl-2-phenoxyquinolin-7-yl)-7H-pyτrolo[2,3- d]pyrimidin-4-ylamine;

4-[4-Amino-5-(2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(2-pyridin-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(2-phenoxyquinolin-7-yl)-pyττolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(2-phenoxyquinolin-7-yl)-pyrrolo[2 ₎ 3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(2-pyridin-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrτolo[2,3-d]pyrimidin-7-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(6-chloro-2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(6-chloro-2-phenoxyquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclohexanecarboxylic acid amide;

7-(4-Aminomethylcyclohexyl)-5-(2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(2-pyridin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-7H-ρyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-chloro-2-phenoxyquinolin-7-yl)-7H-pyττolo[2 _J 3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-chloro-2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine;

7-(4-Aminomethylcyclohexyl)-5-(4-methyl-2-phenylquinohn-7-yl)-7H-pyrrolo[2,3-d]pyriinidin-4- ylamine,

7-(4-Arninornethylcyclohexyl)-5-(4-methyl-2-thiophen-2-ylquinohn-7-yl)-7H-pyrrolo[2,3-d]pyπmidin-4- ylamine,

7-(4-Aminomethylcyclohexyl)-5-(4-methyl-2-phenoxyquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine,

7-(4-Aminomethylcyclohexyl)-5-(4-methyl-2-pyπdin-2-ylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4- ylamine, l-(4-Aminomethylcyclohexyl)-3-(2-thiophen-2-ylquinohn-7-yl)-lH-pyrazolo[3,4-d]pyπmidin-4- ylamine, l-(4-Aminomethylcyclohexyl)-3-(2-pyπdin-2-yl-quinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine, l-(4-Aminomethylcyclohexyl)-3-(2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4-d]pyπmidin-4-ylamine,

1 -(4- Aminomethylcyclohexyl)-3-(2-phenylquinolin-7-yl)- 1 H-pyrazolo[3 ,4-d]pynmidin-4-ylamine; l-(4-Aminomethylcyclohexyl)-3-(6-chloro-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyπmidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(6-chloro-2-pyπdin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyπmidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(6-chloro-2-thiophen-2-ylquinohn-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-

4-ylamine; l-(4-Aminomethylcyclohexyl)-3-(6-chloro-2-phenoxyquinohn-7-yl)-lH-pyrazolo[3,4-d]pyriinidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(4-methyl-2-thiophen-2-ylqumolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidm-

4-ylamme; l-(4-Aminomethylcyclohexyl)-3-(4-methyl-2-pyridin-2-ylquinohn-7-yl)-lH-pyrazolo[3,4-d]pyπmidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(4-methyl-2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine, l-(4-Aminomethylcyclohexyl)-3-(4-methyl-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(4-Aminomethylcyclohexyl)-3-(8-fluoro-2-thiophen-2-yl-quinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-

4-ylamine; l-(4-Aminomethylcyclohexyl)-3-(8-fluoro-2-phenylqumolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l^-AminomethylcyclohexyOO-Cδ-fluoro^-phenoxyquinolin^-yO-lH-pyrazolo^^^pyπmidin-*- ylamine; l^-Aminomethylcyclohexy^^-fδ-fluoro^-pyridm-Z-ylquinolin^-yO-lH-pyrazolotS^-dlpyrimidin^- ylamine;

4-[4-Amino-3-(2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cycIohexanecarboxylic acid amide;

4-[4-Amino-3-(2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(6-chloro-2-phenylquinolin-7-yl)-pyrazoIo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(6-chloro-2-pyridin-2-ylquiπolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidiπ-l-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(6-chloro-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxy]ic acid amide;

4-[4-Amino-3-(8-fluoro-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexaπecarboxylic acid amide;

4-[4-Amino-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(8-fluoro-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(4-methyl-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(4-methyl-2-phenoxyquinolin-7-yl)-ρyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid amide;

4-[4-Amino-3-(2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(6-chloro-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(6-chloro-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(8-fluoro-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(8-fluoro-2-pyridin-2-ylquinolin-7-yl)-pyτazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(8-fluoro-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l -yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(4-methyl-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid methylamide;

4-[4-Amino-3-(4-methyl-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]- cyclohexanecarboxylic acid methylamide; l-Cyclobutyl-3-(2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine; l-Cyclobutyl-3-(2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine; l-Cyclobutyl-3-(2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine;

1 -Cyclobutyl-3-(2-pyridin-2-ylquinolin-7-yl)- 1 H-pyrazolo[3 ,4-d]pyrimidin-4-ylamine;

3-(6-Chloro-2-phenyIquinolin-7-yl)-l-cyclobutyl-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine;

3-(6-Chloro-2-pyridin-2-ylquinolin-7-yl)-l-cyclobutyl-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine;

3-(6-Chloro-2-thiophen-2-ylquinolin-7-yl)- 1 -cyclobutyl- 1 H-pyrazolo[3,4-d]pyrimidin-4-ylamine;

3-(6-Chloro-2-phenoxyquinolin-7-yl)-l-cyclobutyl-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine; l-Cyclobutyl-3-(4-methyl-2-thiophen-2-yIquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine; l-Cyclobutyl-3-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine; l-Cyclobutyl-3-(4-methyl-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine; l-CyclobutylO^-methyl^-phenoxyquinolin^-y^-lH-pyrazoloCS^-djpyrimidin^-ylamine;

3-[4-Amino-B-CZ-phenylquinolin-7-yO-pyrazolofS^-dJpyrimidin-l-yll-cyclobutanol; 3-[4-Amino-S-CZ-pyridin-Z-ylquinolin-y-y^-pyrazolofS^-djpyrimidin-l-ylJ-cyclobutanol;

3-[4-Amino-3-(2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol; 3-[4-Amino-S^-phenoxyquinolin-7-yO-pyrazoloIS^-dJpyrimidin-l-y^-cyclobutanol;

3-[4-Amino-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3 -(6-chloro-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin- 1 -yl]-cyclobutanol;

3-[4-Amino-3-(6-chloro-2-phenoxyquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(4-methyl-2-phenylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l -yl]-cyclobutanol;

3-[4-Amino-3-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol;

3-[4-Amino-3-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-pyrazolo[3,4-d]pyrimidin-l-yl]-cyclobutanol; 3-[4-Amino-S^-methyl^-phenoxyquinolin-7-yl)-pyrazoloP^-djpyrimidin-l-ylJ-cyclobutanol; l-(3-Azetidin-l-ylmethylcyclobutyl)-3-(2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(3-Azetidin-l-ylmethylcyclobutyl)-3-(2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4-ylamine; l-(3-Azetidin-l-ylmethylcyclobutyl)-3-(2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine;

1 -(3-Azetidin-l -ylmethylcyclobutyl)-3-(2-phenoxyquinolin-7-yl)-l H-pyrazolo[3,4-d]pyrimidin-4- ylamine; l -(3-Azetidin-l -ylmethylcyclobutyl)-3-(6-chloro-2-thiophen-2-ylquinolin-7-yl)-l H-pyrazolo[3,4- d]pyrimidin-4-ylamine; l -(3-Azetidin-l -ylmethylcyclobutyl)-3-(6-chloro-2-ρhenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(3-Azetidin-l -ylmethylcyclobutyl)-3-(6-chloro-2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-

4-ylamine; l-(3-Azetidin-l -ylmethylcyclobutyl)-3-(6-chloro-2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Azetidin-l-ylmethylcyclobutyl)-3-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Azetidin-l-ylmethylcyclobutyl)-3-(4-methyl-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-

4-ylamine; l -(3-Azetidin-l-ylmethylcyclobutyl)-3-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine;

1 -(3-Azetidin-l -ylmethylcyclobutyOO^-methyl^-phenoxyquinolin-?^!)-! H-pyrazolo[3,4- d]pyrimidin-4-ylamine; l -(3-Dimethylaminomethylcyclobutyl)-3-(2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine;

l-(3-Dimethylaminomethylcyclobutyl)-3-(2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-4- ylamine; l-fS-DimethylaminornethylcyclobutyO-S^-phenoxyquinolin-V-yO-lH-pyrazolofS^-dlpyrimidin^- ylamine;

3-(6-Chloro-2-phenylquinolin-7-yl)-l-(3-dimethylaminomethylcyclobutyl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine;

3-(6-Chloro-2-thiophen-2-ylquinolin-7-yl)-l-(3-dimethylaminomethylcyclobutyl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine;

3-(6-Chloro-2-phenoxyquinolin-7-yl)-l-(3-dimethylaminomethylcyclobutyl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine;

3-(6-Chloro-2-pyridin-2-ylquinolin-7-yl)-l-(3-dimethylaminomethylcyclobutyl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(4-methyl-2-pyridin-2-ylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(4-methyl-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; ^■ l-(3-Dimethylaminomethylcyclobutyl)-3-(4-methyl-2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-fS-Dimethylaminomethylcyclobuty^^^-methyl^-phenoxyquinolin^-y^-lH-pyrazolofS^- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(8-fluoro-2-phenylquinolin-7-yl)-lH-pyrazolo[3,4-d]pyrimidin-

4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(8-fluoro-2-ρyridin-2-ylquinoIin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-(3-Dimethylaminomethylcyclobutyl)-3-(8-fluoro-2-thiophen-2-ylquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine; l-<3-Dimethylaminomethylcyclobutyl)-3-(8-fluoro-2-phenoxyquinolin-7-yl)-lH-pyrazolo[3,4- d]pyrimidin-4-ylamine;

3-Cyclobutyl-l-(3-phenylquinoxalin-6-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

S-tδ-Amino-l-CS-phenylquinoxalin-ό-yO-imidazofl^-aJpyrazin-S-yll-cyclobutanol;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(3-ρhenylquinoxalin-6-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

4-[8-Amino-l -(3-phenylquinoxalin-6-yl)-imidazo[ 1 ,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(3-phenylquinoxalin-6-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylamide;

4-[8-Amino-l-(2-phenylquinazolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

4-[8-Amino-l-(2-phenylquinazolin-7-yl)-imidazo[l,5-a]pyτazin-3-yl]-cyclohexanecarboxylic acid methylamide;

3-Cyclobutyl- 1 -(2-phenylquinazolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-8-ylamine;

S-fδ-Amino-l^-phenylquinazolin-V-yO-imidazotl _j S-alpyrazin-S-ylJ-cyclobutanol;

3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(2-phenylquinazolin-7-yl)-imidazo[l,5-a]pyτazin-8-ylamine;

3-[3-(2-Methoxyethoxy)-cyclobutyl]-l-(2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine; l-(6-Chloro-2-phenylquinolin-7-yl)-3-[3-(2-methoxyethoxy)-cyclobutyl]-imidazo[l ,5-a]pyrazin-8- ylamine;

3-[3-(2-Methoxyethoxy)-cyclobutyl]-l-(4-methyl-2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8- ylamine;

3-(l-Methyl-l,2,3,6-tetrahydropyridin-4-yl)-l-(2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

1 - {4-[8- Amino- 1 -(2-phenylquinolin-7-yl)-imidazo[ 1 ,5 -a]pyrazin-3 -yl]-3 ,6-dihydro-2H-pyridin- 1 -yl } - ethanone;

3-Bicyclo[3.1.0]hex-6-yl-l-(2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

6-[8-Amino-l-(2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-bicyclo[3.1.0]hexan-3-ol;

7-Cyclobutyl-5-(2-phenylquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-4-ylamine;

7-Cyclobutyl-5-(2-thiophen-2-ylquinolin-7-yl)-imidazo[5,l-fl[l,2,4]triazin-4-ylamine;

7-Cyclobutyl-5-(2-phenoxyquinolin-7-yl)-imidazo[5, l-f][l,2,4]triazin-4-ylamine;

7-Cyclobutyl-5-(2-pyridin-2-ylquinolin-7-yl)-imidazo[5, 1 -f] [ 1 ,2,4]triazin-4-ylamine;

3-[4-Amino-5-(2-phenylquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-7-yl]-cyclobutanol;

3-[4-Amino-5-(2-thiophen-2-ylquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-7-yl]-cyclobutanol;

3-[4-Amino-5-(2-phenoxyquinolin-7-yl)-imidazo[5,l-fl[l ,2,4]triazin-7-yl]-cyclobutanol;

3-[4-Amino-5-(2-pyridin-2-ylquinolin-7-yl)-imidazo[5,l-fJ[ 1 ,2,4JtHaZJn-? -yl]-cyclobutanol;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-phenylquJnolin-7-yl)-imidazo[5,l-f][l ,2,4]triazin-4-y]amine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-thiophen-2-ylquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-4- ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-phenoxyquinolin-7-yl)-imidazo[5,l-fJ[l,2,4]triazin-4-ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-pyridin-2-ylquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-4- ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-pyridin-2-ylquinolin-7-yl)-imidazo[5,l-f][l ,2,4]triazin-4- ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-thiophen-2-ylquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-4- ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-phenylquinolin-7-yl)-imidazo[5 ₎ l-f][l,2,4]triazin-4-ylamine;

7-(3-Dimethylaminomethylcyclobutyl)-5-(2-phenoxyquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-4- ylamine;

4-[4-Amino-5-(2-phenylquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(2-thiophen-2-ylquinolin-7-yl)-imidazo[5,l-£][l,2,4]tnazin-7-yl]-cyclohexanecarboxylic acid amide; 4-[4-Amino-5-(2-phenoxyquinolin-7-yl)-imidazo[5,l-f][l,2,4]tπazin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(2-phenylquinolin-7-yl)-imidazo[5,l-f][l ₎ 2,4]tπazin-7-yl]-cyclohexanecarboxyhc acid methylamide;

4-[4-Amino-5-(2-thiophen-2-ylquinolin-7-yl)-imidazo[5,l-f][l ,2,4]tπazin-7-yl]-cyclohexanecarboxylic acid methylamide;

4-[4-Amino-5-(2-phenoxyquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-7-yl]-cyc]ohexanecarboxylic acid methylamide;

7-(4-Aminomethylcyclohexyl)-5-(2-phenylquinohn-7-yl)-imidazo[5,l-f][l,2,4]tnazin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(2-thiophen-2-ylquinolin-7-yl)-imidazo[5,l-f][l ,2,4]triazin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(2-phenoxyquinolin-7-yl)-irmdazo[5, 1 -f] [ 1 ,2,4]tπazin-4-ylamine;

7-(4-Aminomethylcyclohexyl)-5-(6-chloro-2-phenylquinohn-7-yl)-imidazo[5, 1 -f][l ,2,4]triazin-4- ylamine;

4-[4-Amino-5-(6-chloro-2-phenylquinolin-7-yl)-imidazo[5,l-f][l,2,4]triazin-7-yl]-cyclohexanecarboxylic acid amide;

4-[4-Amino-5-(6-chloro-2-phenylquinolin-7-yl)-imidazo[5,l-f][l,2,4]tπazin-7-yl]-cyclohexanecarboxylic acid methylamide;

5-(6-Chloro-2-phenylquinolin-7-yl)-7-cyclobutylimidazo[5,l-f][l,2,4]tnazin-4-ylamine;

3-[4-Amino-5-(6-chloro-2-phenylquinolin-7-yl)-imidazo[5,l-f][l,2,4]tπazin-7-yl]-cyclobutanol;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(6-chloro-2-phenylquinohn-7-yl)-imidazo[5,l-fI[l,2,4]tnazin-4- ylamine;

7-(3-Azetidin-l-ylmethylcyclobutyl)-5-(2-phenylquinolin-7-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-ylamine; 3-[4-Ammo-5-(2-phenylquinohn^-y^-SH-pyrrolofS^-dJpyrimidin^-ylJ-cyclobutanol;

7-Cyclobutyl-5-(2-phenylquinolin-7-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-ylamine;

7-Phenyl-5-(2-phenylquinolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine;

3-Isopropyl-l -(2-phenylquinolin-7-yl)-imidazo[ 1 ,5-a]pyrazin-8-ylamine;

3-tert-Butyl-l -(2-phenylquinohn-7-yl)-imidazo[l,5-a]pyrazin-8-ylamine;

5-[8-Amino-l -(2-phenylquinolm-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-pyrrolidin-3-ol;

3-Cyclobutyl-l-(2-phenylquinolin-7-yl)-2H-imidazo[l,5-α]pyrazin-8-ylamine;

/ro«j- 4-[8-Amino-l-(2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide;

/rα/?-?-4-[8-Amino-l-(2-phenylquinolin-7-yl)-imidazo[l,5-α]pyrazin-3-yl]-cyclohexanecarboxylic acid methyl ester; trans-4-[8-Amino-l -(2-phenylquinohn-7-yl)-imidazo[ 1 ,5-α]pyrazin-3-yl]-cyclohexanecarboxyhc acid;

/rαns-4-[8-Amino-l-(2-phenylquinolin-7-yl)-imidazo[l ,5-α]pyrazin-3-yl]-cyclohexanecarboxyhc acid methylamide;

/ra«5-{4-[8-Amino-l(2-phenylquinolin-7-yl)-imidazo[l,5-a]pyrazin-3-yl]-cyclohexyl}-niethanol; /rα/ιs-2-{4-[8-Amino-l-(2-phenylquinolin-7-yl)-imidazo[l,5-α]pyrazin-3-yl]-cyclohexylmethyl}- isoindole-1 ,3-dione;

3-(4-Aminomethyl-cyclohexyl)-l-(2-phenyl-quinolin-7-yl)-imidazo[l,5-a] pyrazin-8-ylamine; ^rαns-3-(4-Aminomethylcyclohexyl)-l -(2-phenylquinolin-7-yl)-imidazo[l ,5-α] pyrazin-8-ylamine; 3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(2-phenylquinolin-7-yl)-imidazo[l ,5-α]pyrazin-8-ylamine; cw-3-(3-Azetidin-l-ylmethylcyclobutyl)-l-(2-phenylquinolin-7-yl)-imidazo[l,5-α]pyrazin-8-ylamine; and {3-[8-Amino-l -(2-phenylquinolin-7-yl)-imidazo[l,5-α]pyrazin-3-yl]-cyclobutyl}-methanol.

40. The method of claim 38, wherein the anti-cancer agent is an EGFR kinase inhibitor, MEK inhibitor, VEGFR inhibitor, anti-VEGFR2 antibody, KDR antibody, AKT inhibitor, PDK-I inhibitor, PI3K inhibitor, c-kit/Kdr tyrosine kinase inhibitor, Bcr-Abl tyrosine kinase inhibitor, VEGFR2 inhibitor, PDGFR-beta inhibitor, KIT inhibitor, Flt3 tyrosine kinase inhibitor, PDGF receptor family inhibitor, Flt3 tyrosine kinase inhibitor, RET tyrosine kinase receptor family inhibitor, VEGF-3 receptor antagonist, Raf protein kinase family inhibitor, angiogenesis inhibitor, Erb2 inhibitor, mTOR inhibitor, IGF-IR antibody, NFkB inhibitor, Proteosome inhibitor, chemotherapy agent, glucose reduction agent, or insulin-sensitizer.

41. The method of claim 38, wherein the anti-cancer agent is ARRY-142886, PD-184352, ZD-6474, IMC-1 121b, CDP-791 , imatinib, sunitinib malate, sorafenib, PTK-787, lapatinib, sirolimus, temsirolimus, everolimus, CP-751871, RAV-12, IMC-A12, 19Dl 2, PS-1145, or orbortezomib.

42. The method of claim 40, wherein the anti-cancer agent is an EGFR kinase inhibitor.

43. The method of claim 42, wherein the EGFR kinase inhibitor is erlotiπib, cetuximab, gefϊtinib, or a salt thereof.

44. The method of claim 43, wherein the EGFR kinase inhibitor is erlotinib or a salt thereof.

45. The method of claim 38, further comprising combining a pharmaceutically acceptable carrier with the IGFR inhibitor and anti-cancer agent.

46. The method of claim 18, wherein the anti-cancer agent is a MEK inhibitor.

47. The method of claim 46, wherein the MEK inhibitor is ARRY-142886, PD-184352, or PD- 98059.

48. The method of claim 19, wherein the anti-cancer agent is a MEK inhibitor.

49. The method of claim 48, wherein the MEK inhibitor is ARRY-142886, PD-184352, or PD- 98059.

50. The method of claim 20, wherein the anti-cancer agent is a MEK inhibitor.

51. The method of claim 50, wherein the MEK inhibitor is ARRY-142886, PD- 184352, or PD- 98059.

52. The method of claim 18, wherein the anti-cancer agent is a Raf protein kinase family inhibitor.

53. The method of claim 52, wherein the Raf protein kinase family inhibitor is sorafenib.

54. The method of claim 19, wherein the anti-cancer agent is a Raf protein kinase family inhibitor.

55. The method of claim 54, wherein the Raf protein kinase family inhibitor is sorafenib.

56. The method of claim 20, wherein the anti-cancer agent is a Raf protein kinase family inhibitor.

57. The method of claim 56, wherein the Raf protein kinase family inhibitor is sorafenib.