Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors

1. A method of treating cancer, wherein the cancer is lymphoma, leukemia, multiple myeloma or myeloproliferative disorders, comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

Cy is a group of the following formula (Cy-2):

wherein:

R x is H;

R y is H;

a is 1; and

b is 1;

wherein the substituted piperidin-1-yl ring forming Cy is substituted with 1, 2, 3, 4 or 5 substituents each independently selected from halogen, R Cy1 , C 1-6 haloalkyl, CN, 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)NR c1 R d1 , NR c1 C(O)OR a1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , NR c1 S(O) 2 R b1 and S(O) 2 NR c1 R d1 ,

wherein each R Cy1 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-7 cycloalkyl and 4-7 membered heterocycloalkyl, each of which is independently unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, R Cy2 , C 1-6 haloalkyl, CN, 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)NR c1 R d1 , NR c1 C(O)OR a1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , NR c1 S(O) 2 R b1 and S(O) 2 NR c1 R d1 , and

wherein each R Cy2 is independently C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-7 cycloalkyl and 4-7 membered heterocycloalkyl, each of which is independently unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, CN, OR 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)NR c1 R d1 NR c1 C(O)OR a1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 and S(O) 2 NR c1 R d1 ;

A 1 is CR 1 ;

R 1 is H, halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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)NR c2 R d2 , NR c2 C(O)OR a2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , NR c2 S(O) 2 R b2 or S(O) 2 NR c2 R d2 ; and

R 2 is H, halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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)NR c2 R d2 , NR c2 C(O)OR a2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , NR c2 S(O) 2 R b2 or S(O) 2 NR c2 R d2 ;

or A 1 and R 2 in combination, together with the carbon atom to which R 2 is attached, form a 5, 6 or 7-membered unsaturated or partially saturated carbocyclic or heterocyclic ring containing 3 to 7 ring carbon atoms and 0, 1 or 2 ring heteroatoms, each independently selected from N, O and S, wherein the ring formed by the combination of A 1 and R 2 is unsubstituted or substituted by 1, 2 or 3 substituents independently selected from halogen, C 1-6 alkyl, 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 c C(O)R b2 , NR c2 C(O)NR c2 R d2 , NR c2 C(O)OR a2 and oxo;

R 3 is NH 2 ;

R 4 is H;

A 5 is N or CR 5 ;

A 6 is N or CR 6 ;

A 7 is N or CR 7 ;

A 8 is N or CR 8 ;

provided that 0, 1 or 2 of A 5 , A 6 , A 7 and A 8 are N;

R 5 is H or halogen;

R 6 is H or halogen;

R 7 is H, halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, Cy 7 , -L 7 -Cy 7 , CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 or S(O) 2 NR c3 R d3 ,

wherein said C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl forming R 7 are each independently unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, OR a3 SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 and S(O) 2 NR c3 R d3 ;

Cy 7 is unsubstituted or substituted C 6-10 aryl, unsubstituted or substituted 5-10 membered heteroaryl, unsubstituted or substituted C 3-6 cycloalkyl or unsubstituted or substituted 4-7 membered heterocycloalkyl,

wherein the substituted C 6-10 aryl, 5-10 membered heteroaryl, C 3-6 cycloalkyl or 4-7 membered heterocycloalkyl forming Cy 7 is substituted with 1, 2, 3, 4 or 5 substituents each independently selected from halogen, R Cy7 , C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 and S(O) 2 NR c3 R d3 ,

wherein each R Cy7 is C 1-6 alkyl, each of which is independently unsubstituted or substituted by 1, 2 or 3 substituents independently selected from halogen, CN, OR a3 SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 and S(O) 2 NR c3 R d3 ;

L 7 is unsubstituted C 1-6 alkylene or C 1-6 alkylene substituted with 1, 2 or 3 substituents independently selected from F, Cl, CN, OH, O(C 1-6 alkyl), NH 2 , NH(C 1-6 alkyl) and N(C 1-6 alkyl) 2 ;

R 8 is H, halogen, CN or C 1-6 alkyl;

R a1 , R b1 , R c1 and R d1 are each independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-3 alkyl, 5-10 membered heteroaryl-C 1-3 alkyl, C 3-7 cycloalkyl-C 1-3 alkyl and 4-10 membered heterocycloalkyl-C 1-3 alkyl, wherein said C 6-10 aryl-C 1-3 alkyl, 5-10 membered heteroaryl-C 1-3 alkyl, C 3-7 cycloalkyl-C 1-3 alkyl and 4-10 membered heterocycloalkyl-C 1-3 alkyl forming R a1 , R b1 , R c1 and R d1 are each optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from C 1-6 alkyl, halo, CN, OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , OC(O)R b4 , OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , NR c4 C(O)NR c4 R d4 , NR c4 C(O)OR a4 , C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )NR c4 R d4 S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , NR c4 S(O) 2 R b4 and S(O) 2 NR c4 R d4 ;

or R c1 and R d1 attached to the same N atom, together with the N atom to which they are both attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or 5-membered heteroaryl group, each optionally substituted with 1, 2 or 3 substituents independently selected from C 1-6 alkyl, halo, CN, OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , OC(O)R b4 , OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , NR c4 C(O)NR c4 R d4 , NR c4 C(O)OR a4 , C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )NR c4 R d4 S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , NR c4 S(O) 2 R b4 and S(O) 2 NR c4 R d4 ;

R a2 , R b2 , R c2 and R d2 are each independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-3 alkyl, 5-10 membered heteroaryl-C 1-3 alkyl, C 3-7 cycloalkyl-C 1-3 alkyl and 4-10 membered heterocycloalkyl-C 1-3 alkyl, wherein said C 6-10 aryl-C 1-3 alkyl, 5-10 membered heteroaryl-C 1-3 alkyl, C 3-7 cycloalkyl-C 1-3 alkyl and 4-10 membered heterocycloalkyl-C 1-3 alkyl forming R a2 , R b2 , R c2 and R d2 , are each optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from C 1-6 alkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 and S(O) 2 NR c5 R d5 ;

or R c2 and R d2 , attached to the same N atom, together with the N atom to which they are both attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or 5-membered heteroaryl group, each optionally substituted with 1, 2 or 3 substituents independently selected from C 1-6 alkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 SR d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 and S(O) 2 NR c5 R d5 ;

R a3 , R b3 , R c3 and R d3 are each independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-3 alkyl, 5-10 membered heteroaryl-C 1-3 alkyl, C 3-7 cycloalkyl-C 1-3 alkyl and 4-10 membered heterocycloalkyl-C 1-3 alkyl, wherein said C 6-10 aryl-C 1-3 alkyl, 5-10 membered heteroaryl-C 1-3 alkyl, C 3-7 cycloalkyl-C 1-3 alkyl and 4-10 membered heterocycloalkyl-C 1-3 alkyl forming R a3 , R b3 , R c3 and R d3 are each optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from C 1-6 alkyl, halo, CN, OR a6 , SR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , OC(O)R b6 , OC(O)NR c6 R d6 , NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)NR c6 R d6 , NR c6 C(O)OR a6 , C(═NR e6 )NR c6 R d6 , NR c6 C(═NR e6 )NR c6 R d6 S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , NR c6 S(O) 2 R b6 and S(O) 2 NR c6 R d6 ;

or R c3 and R d3 attached to the same N atom, together with the N atom to which they are both attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or 5-membered heteroaryl group, each optionally substituted with 1, 2 or 3 substituents independently selected from C 1-6 alkyl, halo, CN, OR a6 , SR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , OC(O)R b6 , OC(O)NR c6 R d6 , NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)NR c6 R d6 , NR c6 C(O)OR a6 , C(═NR e6 )NR c6 R d6 , NR c6 C(═NR e6 )NR c6 R d6 S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , NR c6 S(O) 2 R b6 and S(O) 2 NR c6 R d6 ;

R a4 , R b4 , R c4 and R d4 are each independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, C 6-10 aryl-C 1-3 alkyl, 5-10 membered heteroaryl-C 1-3 alkyl, C 3-7 cycloalkyl-C 1-3 alkyl and 4-10 membered heterocycloalkyl-C 1-3 alkyl, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl C 6-10 aryl-C 1-3 alkyl, 5-10 membered heteroaryl-C 1-3 alkyl, C 3-7 cycloalkyl-C 1-3 alkyl and 4-10 membered heterocycloalkyl-C 1-3 alkyl forming R a4 , R b4 , R c4 and R d4 are each optionally substituted with 1, 2 or 3 substituents independently selected from OH, CN, amino, NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl and C 1-6 haloalkoxy;

or R c4 and R d4 attached to the same N atom, together with the N atom to which they are both attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or 5-membered heteroaryl group, each optionally substituted with 1, 2 or 3 substituents independently selected from OH, CN, amino, NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl and C 1-6 haloalkoxy;

R a5 , R b5 , R c5 and R d5 are each independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, C 6-10 aryl-C 1-3 alkyl, 5-10 membered heteroaryl-C 1-3 alkyl, C 3-7 cycloalkyl-C 1-3 alkyl and 4-10 membered heterocycloalkyl-C 1-3 alkyl, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl C 6-10 aryl-C 1-3 alkyl, 5-10 membered heteroaryl-C 1-3 alkyl, C 3-7 cycloalkyl-C 1-3 alkyl and 4-10 membered heterocycloalkyl-C 1-3 alkyl forming R a5 , R b5 , R c5 and R d5 are each optionally substituted with 1, 2 or 3 substituents independently selected from OH, CN, amino, NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl and C 1-6 haloalkoxy;

or R c5 and R d5 attached to the same N atom, together with the N atom to which they are both attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or 5-membered heteroaryl group, each optionally substituted with 1, 2 or 3 substituents independently selected from OH, CN, amino, NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl and C 1-6 haloalkoxy;

R a6 , R b6 , R c6 and R d6 are each independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, C 6-10 aryl-C 1-3 alkyl, 5-10 membered heteroaryl-C 1-3 alkyl, C 3-7 cycloalkyl-C 1-3 alkyl and 4-10 membered heterocycloalkyl-C 1-3 alkyl, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl C 6-10 aryl-C 1-3 alkyl, 5-10 membered heteroaryl-C 1-3 alkyl, C 3-7 cycloalkyl-C 1-3 alkyl and 4-10 membered heterocycloalkyl-C 1-3 alkyl forming R a6 , R b6 , R c6 and R d6 are each optionally substituted with 1, 2 or 3 substituents independently selected from OH, CN, amino, NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl and C 1-6 haloalkoxy;

or R c6 and R d6 attached to the same N atom, together with the N atom to which they are both attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or 5-membered heteroaryl group, each optionally substituted with 1, 2 or 3 substituents independently selected from OH, CN, amino, NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl and C 1-6 haloalkoxy; and

R e1 , R e2 , R e3 , R e4 , R e5 and R e6 are each, independently, H, CN or NO 2 .

2. The method of claim 1 , wherein the cancer is a cancer wherein the expression or activity of at least one of Pim1, Pim2 and Pim3 is upregulated.

3. The method of claim 1 , wherein R 1 is H, halogen or C 1-6 alkyl.

4. The method of claim 1 , wherein R 1 is H.

5. The method of claim 1 , wherein R 2 is H, halogen, CN, C 1-6 alkyl or C 1-6 alkoxy.

6. The method of claim 1 , wherein R 2 is H.

7. The method of claim 1 , wherein A 1 and R 2 in combination, together with the carbon atom to which R 2 is attached, form a 5, 6 or 7-membered unsaturated or partially saturated carbocyclic or heterocyclic ring containing 3 to 7 ring carbon atoms and 0, 1 or 2 ring heteroatoms, each independently selected from N, O and S; wherein the ring formed by the combination of A 1 and R 2 is unsubstituted or substituted by 1, 2 or 3 substituents independently selected from halogen, C 1-6 alkyl, CN, OR a2 , OC(O)R a2 and oxo.

8. The method of claim 7 , wherein R 1 and R 2 in combination form a C 3-5 alkylene that is unsubstituted or substituted by OR a2 .

9. The method of claim 8 , wherein R 1 and R 2 in combination form a C 3-5 alkylene that is unsubstituted or substituted by OH.

10. The method of claim 1 , wherein A 5 is CR 5 .

11. The method of claim 10 , wherein R 5 is H.

12. The method of claim 1 , wherein A 6 is N.

13. The method of claim 1 , wherein A 6 is CR 6 .

14. The method of claim 13 , wherein R 6 is H.

15. The method of claim 13 , wherein R 6 is halogen.

16. The method of claim 1 , wherein A 7 is N.

17. The method of claim 1 , wherein A 7 is CR 7 .

18. The method of claim 17 , wherein R 7 is H, halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 or S(O) 2 NR c3 R d3 , wherein said C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl forming R 7 are each unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR 3 C(O)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR 3 S(O) 2 R b3 and S(O) 2 NR c3 R d3 .

19. The method of claim 18 , wherein R 7 is H, halogen, C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, wherein said C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl forming R 7 are each unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, OR a3 , OC(O)R b3 , NR c3 R d3 and NR c3 C(O)R b3 .

20. The method of claim 19 , wherein R 7 is H, halogen or C 1-6 alkyl, wherein said C 1-6 alkyl forming R 7 is unsubstituted or substituted with a substituent selected from halogen, CN, OR a3 , OC(O)R b3 , NR c3 R d3 and NR 3 C(O)R b3 .

21. The method of claim 20 , wherein R 7 is H, halogen, C 1-6 alkyl, (C 1 -6 alkylene)-CN, (C 1-6 alkylene)-OH, (C 1-6 alkylene)-O(C 1-6 alkyl) or (C 1-6 alkylene)-NR c3 R d3 .

22. The method of claim 21 , wherein R 7 is H, halogen, methyl, ethyl, isopropyl, CH 2 CN, CH(OH)CH 3 , C(OH)(CH 3 ) 2 , CFCH 3 or CH 2 N(CH 3 ) 2 .

23. The method of claim 17 , wherein R 7 is Cy 7 or -L 7 -Cy 7 .

24. The method of claim 23 , wherein Cy 7 is unsubstituted C 6-10 aryl or C 6-10 aryl substituted with 1, 2, 3, 4 or 5 substituents each independently selected from halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 and S(O) 2 NR c3 R d3 .

25. The method of claim 24 , wherein Cy 7 is unsubstituted phenyl or phenyl substituted with 1, 2, 3, 4 or 5 substituents each independently selected from halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 and S(O) 2 NR c3 R d3 .

26. The method of claim 25 , wherein Cy 7 is unsubstituted phenyl, 2,6-difluorophenyl, 2-carbamylphenyl, 2-carbamyl-6-fluorophenyl, 2-cyanophenyl, 2-cyano-6-fluorophenyl.

27. The method of claim 23 , wherein Cy 7 is unsubstituted 5-10 membered heteroaryl or 5-10 membered heteroaryl substituted with 1, 2, 3, 4 or 5 substituents each independently selected from halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 and S(O) 2 NR c3 R d3 .

28. The method of claim 27 , wherein Cy 7 is unsubstituted pyrazolyl or pyrazolyl substituted with 1, 2 or 3 C 1-6 alkyl substituents.

29. The method claim 23 , wherein Cy 7 is unsubstituted C 3-7 cycloalkyl or C 3-7 cycloalkyl substituted with 1, 2, 3, 4 or 5 substituents each independently selected from halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 and S(O) 2 NR c3 R d3 .

30. The method of claim 29 , wherein Cy 7 is unsubstituted C 3-7 cycloalkyl.

31. The method of claim 23 , wherein Cy 7 is unsubstituted 4-7 membered heterocycloalkyl or 4-7 membered heterocycloalkyl substituted with 1, 2, 3, 4 or 5 substituents each independently selected from halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 and S(O) 2 NR c3 R d3 .

32. The method of claim 31 , wherein Cy 7 is unsubstituted 4-7 membered heterocycloalkyl.

33. The method of claim 31 , wherein Cy 7 is morpholinyl, piperidinyl, pyrrolidinyl or tetrahydropyranyl.

34. The method of claim 23 , wherein R 7 is -L 7 -Cy 7 and L 7 is unsubstituted C 1-6 alkylene.

35. The method of claim 34 , wherein L 7 is CH 2 .

36. The method of claim 23 , wherein R 7 is -L 7 -Cy 7 and L 7 is C 1-6 alkylene substituted with 1, 2 or 3 substituents independently selected from F, Cl, CN, OH, O(C 1-6 alkyl), NH 2 , NH(C 1-6 alkyl) and N(C 1-6 alkyl) 2 .

37. The method of claim 36 , wherein L 7 is C 1-6 alkylene substituted with 1 substituent selected from CN, OH, O(C 1-6 alkyl), NH 2 , NH(C 1-6 alkyl) and N(C 1-6 alkyl) 2 or 1, 2 or 3 substituents independently selected from F and Cl.

38. The method of claim 37 , wherein L 7 is —CH(OH)—.

39. The method of claim 1 , wherein A 8 is N.

40. The method of claim 1 , wherein A 8 is CR 8 .

41. The method of claim 40 , wherein R 8 is H.

42. The method of claim 1 , wherein R a1 , R b1 , R c1 , R d1 , R a2 , R b2 , R c2 , R d2 , R a3 , R b3 , R c3 , R d3 , R a4 , R b4 , R c4 , R d4 , R a5 , R b5 , R c5 , R d5 , R a6 , R b6 , R c6 and R d6 are each independently selected from H and C 1-6 alkyl and R e1 , R e2 , R e3 , R e4 , R e5 and R e6 are each H.

43. The method of claim 1 , wherein A 5 is CR 5 and A 7 is CR 7 .

44. The method of claim 1 , wherein A 5 is CR 5 , A 6 is CR 6 and A 7 is CR 7 .

45. A method of treating cancer, wherein the cancer is lymphoma, leukemia, multiple myeloma or myeloproliferative disorders, comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound selected from the following compounds, or a pharmaceutically acceptable salt thereof:

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-piperidin-4-ylquinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-(tetrahydro-2H-pyran-4-yl)quinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-(2,6-difluorophenyl)quinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-(1-methyl-1H-pyrazol-5-yl)quinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-(2-cyanophenyl)quinoline-2-carboxamide;

3-amino-7-[2-(aminocarbonyl)phenyl]-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl)}quinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-(2-cyano-6-fluorophenyl)quinoline-2-carboxamide;

3-amino-7-[2-(aminocarbonyl)-6-fluorophenyl]-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}quinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-isopropylquinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-ethylquinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}quinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-bromoquinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-(cyanomethyl)quinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-ethyl-6-fluoroquinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-(1-hydroxyethyl)quinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-(1-hydroxy-1-methylethyl)quinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-[hydroxy(phenyl)methyl]quinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-(1-fluoroethyl)quinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-(pyrrolidin-1-ylmethyl)quinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-[(dimethylamino)methyl]quinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-(morpholin-4-ylmethyl)quinoline-2-carboxamide; and

3-amino-N-{4-[3-aminopiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-7-ethylquinoline-2-carboxamide;

3-amino-N-[4-(3-aminocyclohexyl)pyridin-3-yl]-7-ethylquinoline-2-carboxamide;

3-amino-N-(4-(3-aminopiperidin-1-yl)-2,3-dihydrofuro[2,3-b]pyridin-5-yl)-7-ethylquinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-ethoxy-1,8-naphthyridine-2-carboxamide;

3-amino-N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-ethoxy-1, 8-naphthyridine-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]pyridin-3-yl}-7-ethyl-1,6-naphthyridine-2-carboxamide;

3-amino-N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]-5-methylpyridin-3-yl}-7-ethylquinoline-2-carboxamide;

3-amino-N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-ethylquinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]-5-methylpyridin-3-yl}-7-ethylquinoline-2-carboxamide;

3-amino-N-{4-[3-aminopiperidin-1-yl]-6-methoxypyridin-3-yl}-7-ethylquinoline-2-carboxamide; and

3-amino-N-{4-[3-aminopiperidin-1-yl]-5-cyanopyridin-3-yl}-7-ethylquinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-piperidin-4-ylquinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(tetrahydro-2H-pyran-4-yl)quinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(2,6-difluorophenyl)quinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(1-methyl-1H-pyrazol-5-yl)quinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(2-cyanophenyl)quinoline-2-carboxamide;

3-amino-7-[2-(aminocarbonyl)phenyl]-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}quinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(2-cyano-6-fluorophenyl)quinoline-2-carboxamide;

3-amino-7-[2-(aminocarbonyl)-6-fluorophenyl]-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl)}quinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-isopropylquinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-ethylquinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}quinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-bromoquinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(cyanomethyl)quinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-ethyl-6-fluoroquinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(1-hydroxyethyl)quinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(1-hydroxy-1-methylethyl)quinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-[hydroxy(phenyl)methyl]quinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(1-fluoroethyl)quinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(pyrrolidin-1-ylmethyl)quinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-[(dimethylamino)methyl]quinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(morpholin-4-ylmethyl)quinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-7-ethylquinoline-2-carboxamide;

3-amino-N-[4-(3-aminocyclohexyl)pyridin-3-yl]-7-ethylquinoline-2-carboxamide;

(S)-3-amino-N-(4-(3-aminopiperidin-1-yl)-2,3-dihydrofuro[2,3-b]pyridin-5-yl)-7-ethylquinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-ethoxy-1,8-naphthyridine-2-carboxamide;

3-amino-N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-ethoxy-1,8-naphthyridine-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-ethyl-1,6-naphthyridine-2-carboxamide;

3-amino-N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]-5-methylpyridin-3-yl}-7-ethylquinoline-2-carboxamide;

3-amino-N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-ethylquinoline-2-carboxamide;

3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]-5-methylpyridin-3-yl}-7-ethylquinoline-2-carboxamide;

3-amino-N-{4-[(3 S)-3-aminopiperidin-1-yl]-6-methoxypyridin-3-yl}-7-ethylquinoline-2-carboxamide; and

3-amino-N-{4-[(3 S)-3-aminopiperidin-1-yl]-5-cyanopyridin-3-yl}-7-ethylquinoline-2-carboxamide.

46. The method of claim 1 , wherein the compound is 3-Amino-N-{4-[(3 S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-ethyl-6-fluoroquinoline-2-carboxamide, or a pharmaceutically acceptable salt thereof.

47. The method of claim 1 , wherein the cancer is lymphoma.

48. The method of claim 47 , wherein the lymphoma is diffuse large B-cell lymphoma, mantle cell lymphoma, non-Hodgkin lymphoma, or Hodgkin lymphoma.

49. The method of claim 1 , wherein the cancer is leukemia.

50. The method of claim 49 , wherein leukemia is acute lymphoblastic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, or chronic myelogenous leukemia.

51. The method of claim 1 , wherein the cancer is multiple myeloma.

52. The method of claim 1 , wherein the cancer is myeloproliferative disorders.

53. The method of claim 52 , wherein the myeloproliferative disorder is polycythemia vera (PV), essential thrombocythemia (ET), chronic myelogenous leukemia (CML), primary myelofibrosis (PMF), myelofibrosis with myeloid metaplasia (MMM), post-polycythemia vera/essential thrombocythemia myelofibrosis (Post-PV/ET MF), post-essential thrombocythemia myelofibrosis (Post-ET MF) or post-polycythemia vera myelofibrosis (Post-PV MF).