Pyrazolopyrimidine compounds and uses thereof

1. A method for treating a cancer in a patient, said method comprising: administering to the patient in need thereof a therapeutically effective amount of a compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from Cy 1 , C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c S(O)R b , NR c S(O) 2 R b , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; wherein said C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 ;

Cy 1 is selected from C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from It′;

Cy A is selected from C 6-10 aryl and 5-10 membered heteroaryl; wherein the 5-10 membered heteroaryl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of the 5-10 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R 20 ;

each R 10 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, NO 2 , OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR d1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , C(═NR e1 )R b1 , C(═NOR a1 )R b1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 , NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;

or two R 10 substituents taken together with the carbon atom to which they are attached form a spiro 3-7-membered heterocycloalkyl ring, or a spiro C 3-6 cycloalkyl ring; wherein each spiro 3-7-membered heterocycloalkyl ring has at least one ring-forming carbon atom and 1, 2 or 3, ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of each spiro 3-7-membered heterocycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the spiro 3-7-membered heterocycloalkyl ring and spiro C 3-6 cycloalkyl ring are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 11 ;

each R 11 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , NR c3 S(O)OR a3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;

each R 12 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)OR a5 , NR c5 S(O)R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R 20 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, NO 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , C(═NR e2 )R b2 , C(═NOR a2 )R b2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ;

or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused 4-, 5-, 6- or 7-membered heterocycloalkyl ring, or a fused C 3-7 cycloalkyl ring; wherein the fused 4-, 5-, 6- or 7-membered heterocycloalkyl ring each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of each fused 4-, 5-, 6- or 7-membered heterocycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the fused 4-, 5-, 6- or 7-membered heterocycloalkyl ring and fused C 3-7 cycloalkyl ring are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 21 ;

each R 21 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , NR c4 R d4 , NR c4 C(O)R b4 , NR c4 C(O)OR a4 , NR c4 S(O)R b4 , NR c4 S(O) 2 R b4 , NR c4 S(O) 2 NR c4 R d4 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , and S(O) 2 NR c4 R d4 ; wherein in said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 22 ;

or two R 21 substituents taken together with the carbon atom to which they are attached form a spiro 3-7-membered heterocycloalkyl ring, or a spiro C 3-6 cycloalkyl ring; wherein each spiro 3-7-membered heterocycloalkyl ring has at least one ring-forming carbon atom and 1, 2 or 3 ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of each spiro 3-7-membered heterocycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the spiro 3-7-membered heterocycloalkyl ring and spiro C 3-6 cycloalkyl ring are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 22 ;

each R 22 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, CN, OR a6 , SR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)OR a6 , NR c6 S(O)R b6 , NR c6 S(O) 2 R b6 , NR c6 S(O) 2 NR c6 R d6 , S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , and S(O) 2 NR c6 R d6 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R a , R c , and R d is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 ;

or any R c and R d attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ;

each R b is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 ;

each R a1 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;

or any R c1 and R d1 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 11 ;

each R b1 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;

each R c1 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, amino sulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;

each R a2 , R c2 , and R d2 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ;

or any R c2 and R d2 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 21 ;

each R b2 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ;

each R e2 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, amino sulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;

each R a3 , R c3 and R d3 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;

or any R c3 and R d3 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from R 12 ;

each R b3 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;

each R a4 , R c4 and R d4 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 22 ;

or any R c4 and R d4 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from R 22 ;

each R b4 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 22 ;

each R a5 , R c5 and R d5 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R b5 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R a6 , R c6 and R d6 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;

each R b6 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; and

each R g is independently selected from OH, NO 2 , CN, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-2 alkylene, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-3 alkoxy-C 1-3 alkyl, C 1-3 alkoxy-C 1-3 alkoxy, HO—C 1-3 alkoxy, HO—C 1-3 alkyl, cyano-C 1-3 alkyl, H 2 N—C 1-3 alkyl, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino, thio, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, carboxy, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, aminosulfonyl, C 1-6 alkylaminosulfonyl, di(C 1-6 alkyl)aminosulfonyl, aminosulfonylamino, C 1-6 alkylaminosulfonylamino, di(C 1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-6 alkylaminocarbonylamino, and di(C 1-6 alkyl)aminocarbonylamino;

provided that:

1) R 1 is other than NHC(O)CH 2 CH 2 CH 3 ; and

2) when Cy A is unsubstituted or substituted pyrazol-4-yl, then R 1 is other than pyridin-4-yl substituted by morpholine; and

wherein the cancer is selected from breast cancer, colorectal cancer, lung cancer, ovarian cancer, and pancreatic cancer.

2. The method of claim 1 , wherein R 1 is selected from Cy 1 , C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , and NR c C(O)R b ; wherein said C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 .

3. The method of claim 1 , wherein R 1 is selected from Cy 1 , C 2-6 alkenyl, C 2-6 alkynyl and OR a ; wherein said C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 .

4. The method of claim 1 , wherein R 1 is C 2-6 alkenyl; wherein said C 2-6 alkenyl is optionally substituted with 1, 2, or 3 substituents independently selected from R 10 .

5. The method of claim 1 , wherein R 1 is CHCH substituted with R 10 , and R 10 is phenyl substituted with 4-methylpiperazin-1-yl.

6. The method of claim 1 , wherein R 1 is Cy 1 .

7. The method of claim 1 , wherein Cy 1 is selected from 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 .

8. The method of claim 1 , wherein Cy 1 is C 6-10 aryl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 .

9. The method of claim 1 , wherein Cy 1 is 5-10 membered heteroaryl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 .

10. The method of claim 1 , wherein Cy 1 is phenyl, pyrazolyl, pyridinyl, pyrimidinyl, thiophenyl, and pyridone; wherein the phenyl, pyrazolyl, pyridinyl, pyrimidinyl, thiophenyl, or pyridone are each optionally substituted with 1, 2 or 3 substituents independently selected from R 10 .

11. The method of claim 1 , wherein each R 10 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, NO 2 , OR C(O)OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , S(O)R b1 , S(O) 2 NR c1 R d1 , S(O) 2 NR c1 R d1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 .

12. The method of claim 1 , wherein each R 10 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, OR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , NR c1 R d1 , and NR c1 C(O)R b1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 .

13. The method of claim 1 , wherein each R 10 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 4-10 membered heterocycloalkyl-C 1-3 alkylene, halo, CN, OR a1 , C(O)R b1 , C(O)NR c1 R d1 , and NR c1 R d1 ; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 4-10 membered heterocycloalkyl-C 1-3 alkylene are each optionally substituted with 1, 2, or 3 substituents independently selected from R 11 .

14. The method of claim 1 , wherein each R 11 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, OR a3 , C(O)R b3 , C(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 S(O) 2 R b3 , and S(O) 2 R b3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 .

15. The method of claim 1 , wherein each R 11 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 4-10 membered heterocycloalkyl, halo, CN, OR a3 , C(O)R b3 , NR c3 R d3 , C(O)NR c3 R d3 , NR c3 C(O)R b3 , NR c3 S(O) 2 R b3 , and S(O) 2 R b3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 12 .

16. The method of claim 1 , wherein each R 11 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 4-10 membered heterocycloalkyl, halo, CN, C(O)R b3 , NR c3 R d3 , and NR c3 C(O)R b3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 12 .

17. The method of claim 1 , wherein each R 11 is independently selected from C 1-6 alkyl, 4-10 membered heterocycloalkyl, CN, C(O)R b3 , and NR c3 R d3 ; wherein said C 1-6 alkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 12 .

18. The method of claim 1 , wherein each R 12 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , NR c5 R d5 , or NR c5 C(O)R b5 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g .

19. The method of claim 1 , wherein each R 12 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, and OR a5 .

20. The method of claim 1 , wherein each R 12 is independently OR a5 .

21. The method of claim 1 , wherein each R 12 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl.

22. The method of claim 1 , wherein each R 12 is C 1-6 alkyl.

23. The method of claim 1 , wherein R 10 is 4-methylpiperazin-1-yl, fluoro, methyl, CN, trifluormethyl, methoxy, N,N-dimethylaminocarbonyl, (4-methylpiperazin-1-yl)methyl, 4-morpholinylmethyl, morpholinyl, piperazin-1-yl, pyrrolidin-1-yl, N,N-dimethylamine, morpholinylmethanone, N-cyclopentylaminocarbonyl, 4-(cycloprop-1-yl)morpholine, cyanomethyl, 4-ethylpiperazin-1-yl, N-methylaminocarbonyl, cyclopropyl, pyridin-1-yl, methylamine, 1-methyl-1-cyanomethyl, tetrahydro-2H-pyran-4-yl, phenyl, 1-(piperazin-1-yl)ethan-1-one, 3-hydroxy-piperidin-1-yl, 4-cyano-piperidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, piperidin-4-yl, 4-(2-methyl-2-hydroxypropyl)piperazin-1-yl, 3-methyl-3(methylhydroxy)piperidin-1-yl, 1-(methylsulfonyl)piperidin-4-amino, 4-(ethylhydroxy)piperazin-1-yl, 4-(methylsulfonyl)piperazin-1-yl, 4-((N-methyl-N-ethyl)aminocarbonyl)piperazin-1-yl, piperidin-1-yl, 4-(methylcarbonyl)piperazin-1-yl, 2-cyanophenyl, 1-hydroxyethane-2-amino, (methylsulfonyl)amino-methyl, azetidin-1-ylsulfonyl, difluoromethoxy, 2-(methoxymethyl)morpholin-4-yl, 4-methyl-4-hydroxypiperidin-1-yl, or 4-(2-methoxyethyl)piperazin-1-yl.

24. The method of claim 1 , wherein R 10 is 4-methylpiperazin-1-yl, fluoro, methyl, CN, trifluormethyl, methoxy, N,N-dimethylaminocarbonyl, (4-methylpiperazin-1-yl)methyl, 4-morpholinylmethyl, morpholinyl, piperazin-1-yl, pyrrolidin-1-yl, N,N-dimethylamine, morpholinylmethanone, N-cyclopentylaminocarbonyl, 4-(cycloprop-1-yl)morpholine, cyanomethyl, 4-ethylpiperazin-1-yl, N-methylaminocarbonyl, cyclopropyl, pyridin-1-yl, methylamine, 1-methyl-1-cyanomethyl, tetrahydro-2H-pyran-4-yl, phenyl, or 1-(piperazin-1-yl)ethan-1-one.

25. The method of claim 1 , wherein Cy A is selected from C 6-10 aryl and 6-10 membered heteroaryl; wherein the 6-10 membered heteroaryl has at least one ring-forming carbon atom and 1 or 2 ring-forming N heteroatoms; wherein a ring-forming carbon atom of the 6-10 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the C 6-10 aryl and 6-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 20 .

26. The method of claim 1 , wherein Cy A is phenyl, pyridinyl, isoindolin-1-onyl, or quinolinyl; wherein the phenyl, pyridinyl, and isoindolin-1-onyl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 20 .

27. The method of claim 1 , wherein each R 20 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 4-10 membered heterocycloalkyl, halo, CN, OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 S(O)R b2 ; NR c2 S(O) 2 R b2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ; or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused 4-, 5-, 6- or 7-membered heterocycloalkyl ring, or a fused C 3-7 cycloalkyl ring; wherein the fused 4-, 5-, 6- or 7-membered heterocycloalkyl ring each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of each fused 4-, 5-, 6- or 7-membered heterocycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the fused 4-, 5-, 6- or 7-membered heterocycloalkyl ring and fused C 3-6 cycloalkyl ring are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 21 .

28. The method of claim 1 , wherein each R 20 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 4-10 membered heterocycloalkyl, halo, OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , NR c2 R d2 , and NR c2 C(O)R b2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ; or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused 4-, 5-, 6- or 7-membered heterocycloalkyl ring, or a fused C 3-7 cycloalkyl ring; and wherein the fused 4-, 5-, 6- or 7-membered heterocycloalkyl ring and fused C 3-6 cycloalkyl ring are each optionally substituted with 1 or 2 substituents independently selected from R 21 .

29. The method of claim 1 , wherein each R 20 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , NR c2 R d2 , and NR c2 C(O)R b2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ; or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused 4-, 5-, 6- or 7-membered heterocycloalkyl ring, or a fused C 3-7 cycloalkyl ring.

30. The method of claim 1 , wherein each R 20 is independently selected from C 1-6 alkyl, halo, OR a2 , C(O)R b2 , and C(O)NR c2 R d2 ; or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused 4-, 5-, 6- or 7-membered heterocycloalkyl ring.

31. The method of claim 1 , wherein R 20 is fluoro, methyl, methoxy, chloro, (morpholino)methanone, N-methylaminocarbonyl, aminocarbonyl, (methylamino)methyl, trifluoromethyl, pyrrolidin-2-yl, piperidin-2-yl, ((pyrrolidin-1-yl)methyl)carbonylamino, ((N,N-dimethylamino)methyl)carbonylamino, 1-(methylamino)-ethyl, (ethylamino)methyl, cyanomethyl, N-methylamino, or amino; or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused piperidinyl ring.

32. The method of claim 1 , wherein R 20 is fluoro, methyl, methoxy, chloro, (morpholino)methanone, N-methylaminocarbonyl, or aminocarbonyl; or two adjacent R 2 ° substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused piperidinyl ring.

33. The method of claim 1 , wherein Cy A is 2-fluoro-6-methoxyphenyl.

34. The method of claim 1 , wherein the compound has Formula (IIa1), Formula (IIa2), Formula (IIa3), Formula (IIa4) or Formula (IIa5):

or a pharmaceutically acceptable salt thereof, wherein m is 0, 1, 2, 3, or 4.

35. The method of claim 1 , wherein the compound has Formula (IIb1):

or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, 2, 3, 4 or 5.

36. The method of claim 1 , wherein the compound has Formula (IIc1), Formula (IIc2) or Formula (IIc3):

or a pharmaceutically acceptable salt thereof, wherein m is 0, 1, 2, 3, or 4; and n is 0, 1, 2, 3, 4, or 5.

37. The method of claim 1 , wherein the compound is selected from:

5-(2-Fluorophenyl)-3-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazolo[4,3-d]pyrimidine,

3-(4-(4-Methylpiperazin-1-yl)phenyl)-5-o-tolyl-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-Methoxyphenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-Chloro-6-fluorophenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine,

3-(4-(4-Methylpiperazin-1-yl)phenyl)-5-(pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidine,

3-(4-(4-Methylpiperazin-1-yl)phenyl)-5-(5-methylpyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidine,

6-(3-(4-(4-Methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)isoindolin-1-one,

(5-(3-(4-(4-Methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)pyridin-3-yl)(morpholino)methanone,

N-Methyl-5-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)nicotinamide,

5-(3-(4-(4-Methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline,

5-(2-Fluoro-6-methoxyphenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-Fluoro-6-methoxyphenyl)-3-phenyl-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-Fluoro-6-methoxyphenyl)-3-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-Fluoro-6-methoxyphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-Fluoro-6-methoxyphenyl)-3-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-Fluoro-6-methoxyphenyl)-3-(pyrimidin-5-yl)-1H-pyrazolo[4,3-d]pyrimidine,

4-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)benzonitrile,

5-(2-Fluoro-6-methoxyphenyl)-3-(4-(trifluoromethyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-Fluoro-6-methoxyphenyl)-3-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-Fluoro-6-methoxyphenyl)-3-o-tolyl-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-Fluoro-6-methoxyphenyl)-3-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidine,

4-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-N,N-dimethylbenzamide,

5-(2-Fluoro-6-methoxyphenyl)-3-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine,

4-(4-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)benzyl)morpholine

5-(2-Fluoro-6-methoxyphenyl)-3-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine

4-(4-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)morpholine,

5-(2-Fluoro-6-methoxyphenyl)-3-(3-(piperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-fluoro-6-methoxyphenyl)-3-(3-(pyrrolidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine,

4-(3-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)morpholine,

3-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-N,N-dimethylaniline,

(4-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)(morpholino)methanone,

N-Cyclopentyl-4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)benzamide,

4-(1-(4-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)cyclopropyl)morpholine,

2-(4-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)acetonitrile,

5-(2-Fluoro-6-methoxyphenyl)-3-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-Fluoro-6-methoxyphenyl)-3-(4-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidine,

3-(4-(4-Ethylpiperazin-1-yl)phenyl)-5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidine,

4-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-N-methylbenzamide,

3-(4-Cyclopropylphenyl)-5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-Fluoro-6-methoxyphenyl)-3-(4-(piperidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine,

(4-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)methanamine,

2-(4-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)-2-methylpropanenitrile,

5-(2-Fluoro-6-methoxyphenyl)-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine,

5-(2,3-Difluorophenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine,

5-(2,3-Difluoro-6-methoxyphenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine,

2-Fluoro-3-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzamide,

2-Fluoro-N-methyl-3-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzamide,

5-(2-Fluoro-6-methoxyphenyl)-3-(1-phenyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidine,

4-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1-methylpyridin-2(1H)-one,

5-(2-Fluoro-6-methoxyphenyl)-3-(2-(piperazin-1-yl)pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-Fluoro-6-methoxyphenyl)-3-(2-(4-methylpiperazin-1-yl)pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidine,

5-(2-Fluoro-6-methoxyphenyl)-3-(6-(piperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidine,

4-(5-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)pyridin-2-yl)morpholine,

1-(4-(5-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)pyridin-2-yl)piperazin-1-yl)ethan-1-one,

(E)-5-(2-Fluoro-6-methoxyphenyl)-3-(4-(4-methylpiperazin-1-yl)styryl)-1H-pyrazolo[4,3-d]pyrimidine, and

6-Fluoro-5-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline,

or a pharmaceutically acceptable salt thereof.

38. The method of claim 1 , wherein the compound is selected from:

1-(4-(5-(2-Fluoro-6-methylphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperidin-3-ol;

1-(4-(5-(2-Fluoro-6-methylphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperidine-4-carbonitrile;

5-(2-Fluoro-6-methylphenyl)-3-(4-(piperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine;

1-(4-(5-(2-Fluoro-6-methylphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)pyrrolidin-3-ol;

5-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-N-methylpicolinamide;

4-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-2-fluoro-N-methylbenzamide;

1-(3,5-Difluoro-4-(3-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)-N-methylmethanamine;

3-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)benzonitrile;

1-(3,5-Difluoro-4-(3-(4-(piperidin-4-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)-N-methylmethanamine;

1-(3,5-Difluoro-4-(3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)-N-methylmethanamine;

1-(4-(3-(4-(4-Ethylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,5-difluorophenyl)-N-methylmethanamine;

5-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-2-morpholinonicotinonitrile;

1-(3,5-Difluoro-4-(3-(3-fluoro-2-morpholinopyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)-N-methylmethanamine;

1-(4-(5-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)pyridin-2-yl)piperazin-1-yl)-2-methylpropan-2-ol;

(1-(5-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)pyridin-2-yl)-3-methylpiperidin-3-yl)methanol;

N-(4-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)-1-(methylsulfonyl)piperidin-4-amine;

2-(4-(4-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)ethanol;

1-(3,5-Difluoro-4-(3-(6-(4-(methylsulfonyl)piperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)-N-methylmethanamine;

4-(5-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)pyridin-2-yl)-N-ethyl-N-methylpiperazine-1-carboxamide;

1-(3-Fluoro-4-(3-(6-(piperidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-5-(trifluoromethyl)phenyl)-N-methylmethanamine;

1-(4-(5-(5-(2-Fluoro-4-((methylamino)methyl)-6-(trifluoromethyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)pyridin-2-yl)piperazin-1-yl)ethanone;

1-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)-N-methylmethanamine;

2-(4-(5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1H-pyrazol-1-yl)benzonitrile;

5-(2-Fluoro-6-methyl-4-(pyrrolidin-2-yl)phenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine;

5-(2-Fluoro-6-methyl-4-(piperidin-2-yl)phenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine;

N-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)-2-(pyrrolidin-1-yl)acetamide;

N-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)-2-(dimethylamino)acetamide;

1-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)-N-methylmethanamine;

1-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)-N-methylethanamine;

1-(3-Fluoro-5-methoxy-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)-N-methylmethanamine;

N-(3-Fluoro-5-methoxy-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzyl)ethanamine;

5-(2-Fluoro-6-methoxyphenyl)-3-(3-methyl-1H-pyrazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidine;

3-(Benzyloxy)-5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidine;

6,8-Difluoro-7-(3-(2-(4-methylpiperazin-1-yl)pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;

2-(5-(5-(6,8-Difluoro-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)pyrimidin-2-ylamino)ethanol;

6,8-Difluoro-7-(3-(2-(4-methylpiperazin-1-yl)pyrimidin-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;

5-(5-(6,8-Difluoro-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-N,N-dimethylpyrimidin-2-amine;

5-(5-(6,8-Difluoro-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-N-methylpyrimidin-2-amine;

N-(4-(5-(6,8-Difluoro-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)benzyl)methanesulfonamide;

7-(3-(4-(Azetidin-1-ylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-6,8-difluoro-1,2,3,4-tetrahydroisoquinoline;

7-(3-(6-(Difluoromethoxy)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-6,8-difluoro-1,2,3,4-tetrahydroisoquinoline;

445-(5-(6,8-Difluoro-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)pyridin-2-yl)morpholine;

6,8-Difluoro-7-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;

8-Methoxy-5-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;

8-Fluoro-7-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)quinoline;

5-(4-Methoxypyridin-3-yl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine;

5-(4-Methoxypyridin-3-yl)-3-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidine;

N-Methyl-1-(4-methyl-5-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)pyridin-2-yl)methanamine;

2-(3,5-Difluoro-4-(3-(2-(4-methylpiperazin-1-yl)pyrimidin-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)acetonitrile;

6-Fluoro-5-(3-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;

6-Fluoro-8-methyl-7-(3-(2-(4-methylpiperazin-1-yl)pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;

1-(4-(4-(5-(6-Fluoro-8-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)ethanone;

4-(5-(5-(6-Fluoro-8-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)pyridin-2-yl)morpholine;

6-Fluoro-8-methyl-7-(3-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;

6-Fluoro-8-methyl-7-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;

8-Fluoro-6-methyl-7-(3-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;

4,6-Difluoro-N-methyl-5-(3-(6-morpholinopyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2,3-dihydro-1H-inden-1-amine;

4,6-Difluoro-N-methyl-5-(3-(2-(4-methylpiperazin-1-yl)pyrimidin-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2,3-dihydro-1H-inden-1-amine;

6,8-Difluoro-N-methyl-7-(3-(6-morpholinopyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-amine;

5,7-Difluoro-N-methyl-6-(3-(6-morpholinopyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-amine;

5,7-Difluoro-6-(3-(6-morpholinopyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-amine;

5,7-Difluoro-6-(3-(6-morpholinopyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2,3-dihydro-1H-inden-1-amine;

5-Fluoro-7-methoxy-6-(3-(6-morpholinopyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2,3-dihydro-1H-inden-1-amine;

6-Fluoro-N-methyl-5-(3-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-amine;

6-Fluoro-5-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-amine;

1-(5-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)pyridin-2-yl)-4-methylpiperidin-4-ol;

1-(3,5-Difluoro-4-(3-(4-(4-(2-methoxyethyl)piperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)-N-methylmethanamine;

1-(4-(3-(4-(4-Ethylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3-fluoro-5-(trifluoromethyl)phenyl)-N-methylmethanamine;

3-(4-(4-Ethylpiperazin-1-yl)phenyl)-5-(2-fluoro-6-methyl-4-(piperidin-2-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine; and

(R)-1-(3-Fluoro-4-(3-(6-(2-(methoxymethyl)morpholino)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-5-(trifluoromethyl)phenyl)-N-methylmethanamine;

or a pharmaceutically acceptable salt thereof.

39. The method of claim 1 , wherein the cancer is breast cancer.

40. The method of claim 1 , wherein the cancer is colorectal cancer.

41. The method of claim 1 , wherein the cancer is lung cancer.

42. The method of claim 1 , wherein the cancer is ovarian cancer.

43. The method of claim 1 , wherein the cancer is pancreatic cancer.