IP Library › Granted Patent US 12,384,778

Granted Patent B2

US 12,384,778 · App. 18/243,771 · Granted Aug 12, 2025

Pyrazolopyridine compounds and uses thereof

Inventors: Oleg Vechorkin (Wilmington, DE); Jun Pan (Media, PA); Kai Liu (Chadds Ford, PA); Alexander Sokolsky (Philadelphia, PA); Anlai Wang (Wilmington, DE); Hai Fen Ye (Newark, DE); Qinda Ye (Claymont, DE); Wenqing Yao (Chadds Ford, PA)

Assignee: Incyte Corporation

C07D471/04 C07D519/00

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 12,384,778
App. No.: 18/243,771
Granted: Aug 12, 2025
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting HPK1 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer.

Claims (293)

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, NO 2 , 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 R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NOR a )R b , C(═NR e ) NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , and S(O) 2 NR c R d , 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 10 ;

Cy A is C 6-10 aryl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 20 ;

R 2 is 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, 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 a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)OR a7 , NR c7 S(O)R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , and S(O) 2 NR c7 R d7 ; 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 30 ;

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 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 e1 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 e1 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 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 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(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 , 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 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 ;

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 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 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 C 3-7 cycloalkyl ring; wherein a ring-forming carbon atom of the fused C 3-7 cycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the fused C 3-7 cycloalkyl ring is 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 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 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 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 22 ;

or two R 21 substituents taken together with the carbon atom to which they are attached form a spiro C 3-7 cycloalkyl ring; wherein a ring-forming carbon atom of the spiro C 3-7 cycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the spiro C 3-7 cycloalkyl ring is 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 30 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 a8 , SR a8 , C(O)R b8 , C(O)NR c8 R d8 , C(O)OR a8 , NR c8 R d8 , NR c8 C(O)R b8 , NR c8 C(O)OR a8 , NR c8 S(O)R b8 , NR c8 S(O) 2 R b8 , NR c8 S(O) 2 NR c8 R d8 , S(O)R b8 , S(O)NR c8 R d8 , S(O) 2 R b8 , and S(O) 2 NR c8 R d8 ; 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 and R c 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 ;

each R d 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 ;

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 e 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, aminosulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;

each R a1 , R c1 and R d1 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 e1 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, aminosulfonyl, 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, aminosulfonyl, 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 ;

each R a7 , R c7 , and R d7 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 30 ;

or any R c7 and R d7 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 30 ;

each R b7 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; 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 30 ;

each R a8 , R c8 and R d8 , 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 g ;

or any R c8 and R d8 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 g ;

each R b8 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 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 CH 3 ;

2) R b is other than unsubstituted or substituted piperidine;

3) R b is other than unsubstituted or substituted propyl;

4) when R b is phenyl, then R 10 is other than pyrrolidin-1-ylmethyl; and

5) when Cy A is phenyl or halo-phenyl, then R b is other than cyclopropyl and cyclopentyl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy A is phenyl optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 20 .

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, halo, and OR a2 ; wherein said C 1-6 alkyl and C 3-10 cycloalkyl are each optionally substituted with 1 or 2 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 C 3-7 cycloalkyl ring; and wherein the fused C 3-7 cycloalkyl ring is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 21 .

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from methyl, trifluoromethyl, cyclopropyl substituted with methanamine, fluoro, chloro, hydroxy, methoxy, ethoxy, C(O)NH(CH 2 ) 2 OCH 3 , CO-(3-methoxyazetidin-1-yl), NHC(O)-cyclobutyl, NHC(O)-benzyl, methylamino, dimethylamino, NHC(O)CH 2 -(pyrrolidin-1-yl), NHC(O)-(1-methyl-1H-pyrazol-4-yl), NH(CO)CH 2 -(cyclopentyl), NHC(O)CH 2 -(pyridin-3-yl), NHC(O)CH 2 -(7-azabicyclo[2.2.1]heptan-7-yl), NHC(O)-(7-oxa-2-azaspiro[3.5]nonan-2-yl), NHC(O)CH(CH 3 )-(pyrrolidin-1-yl), NHC(O)NH(CH 2 ) 2 OCH 3 , NHC(O)CH 2 -(azetidin-1-yl), NHC(O)CH 2 -(3,3-dimethylazetidin-1-yl), NHC(O)O-(1-methylpiperidin-4-yl), NHC(O)CH 2 -(dimethylamino), NHC(O)CH 2 -((1R,4S)-2-azabicyclo[2.2.1]heptan-2-yl), NHC(O)(CH 2 ) 2 -(dimethylamino), NHC(O) CH 2 CN, (methylamino)methyl, azetidin-1-ylmethyl, CH 2 NH-(tetrahydro-2H-pyran-4-yl), (isopropylamino)methyl, cyclobutyl-NHCH(CH 3 ) 2 , (methylamino)ethyl, (CH 2 ) 2 NH-(tetrahydro-2H-pyran-4-yl), (CH 2 ) 2 NH-(1-isopropylazetidin-3-yl), OCH 2 -(azetidin-2-yl), tetrahydro-2H-pyran-4-yloxy, OCH 2 -(pyridin-4-yl), OC(O)N(CH 3 ) 2 , OC(O)-(morpholin-4-yl), CH 2 NH-(pyridin-5-yl), CH 2 NH-(1-methyl-1H-pyrazol-3-yl), CH 2 NH(CH 2 ) 2 OH, CH 2 NH-cyclopropyl, (3-methoxypiperidin-1-yl)methyl, (ethylamino)methyl, pyrrolidin-1-ylmethyl, 3-methoxyazetidin-1-yl)methyl, pyrrolidin-2-yl, 1-methylpyrrolidin-2-yl, piperidin-2-yl, CH 2 NHCH 2 CF 3 , CH 2 NH-(3-cyclobutan-1-ol), (1-pyrrolidin-3-ol)methyl, CH 2 NHCH 2 C(CH 3 ) 2 OH, CH 2 NHCH 2 -(1-methyl-1H-imidazol-4-yl), CH 2 NHCH 2 -(oxazol-4-yl), CH 2 NHCH 2 CN, CH(CH 3 )NH(CH 3 ), CH 2 NHC(O)CH 3 , CH 2 NHC(O)O(CH 3 ), difluoromethoxy, cyanomethyl, aminomethyl, (hydroxyl)methyl, amino, CH 2 (3,3-dimethylazetidin-1-yl), CH 2 NH-(3-methoxycyclobutyl), CH 2 NHCH 2 -(1-methylcyclopropyl), and morpholinyl.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from methyl, trifluoromethyl, cyclopropyl substituted with methanamine, fluoro, chloro, hydroxy, methoxy, and ethoxy.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently methoxy or fluoro.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy A is selected from 2-fluoro-6-methoxyphenyl, 1-[1-(3-fluoro-5-phenyl)cyclopropyl]methanamine, 2,6-difluorophenyl, 2,6-dimethylphenyl, 2,4,6-trifluorophenyl, 2-chloro-6-fluorophenyl, 1-hydroxy-3,5-difluoro-phen-4-yl, 2-fluoro-6-methylphenyl, 2-ethoxy-6-fluorophenyl, 2-chloro-6-methoxyphenyl, and 2-fluoro-6-(trifluoromethyl)phenyl.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, NO 2 , 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 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 , and S(O) 2 NR c R d ; 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 10 .

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, OR a , C(O)R b , C(O)NR c R d , C(O)OR a , NR c R d , NR c C(O) R b , and NR c C(O)OR a ; 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 10 .

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from C 2-6 alkenyl, C(O)NR c R d , NR c R d , and NR c C(O)R b , wherein said C 2-6 alkenyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 .

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from C(O)NR c R d , NR c R d , and NR c C(O)R b .

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

each R c is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl;

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

each R b is independently selected from 7-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl; wherein said 7-10 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 .

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

each R c is H;

each R d is independently selected from C 1-6 alkyl and C 6-10 aryl; wherein said C 1-6 alkyl and C 6-10 aryl are each optionally substituted with 1 or 2 substituents independently selected from R 10 ; and

each R b is independently selected from 7-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl; wherein said 7-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 10 .

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is NR c C(O)R b .

15. The compound of claim 14 , or a pharmaceutically acceptable salt thereof, wherein R c is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl of R c are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 ; and R b is 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 of R b are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 .

16. The compound of claim 14 , or a pharmaceutically acceptable salt thereof, wherein R c is H or C 1-6 alkyl; and R b is selected from C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl; wherein said 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 .

17. The compound of claim 14 , or a pharmaceutically acceptable salt thereof, wherein R c is H; and R b is selected from 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl; wherein said 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 10 .

18. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is C(O)NR c R d .

19. The compound of claim 18 , or a pharmaceutically acceptable salt thereof, wherein R c is 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 of R c are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 ; and R d is selected from C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl of R d are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 .

20. The compound of claim 18 , or a pharmaceutically acceptable salt thereof, wherein R c is H; and R d is C 6-10 aryl optionally substituted with 1, 2, or 3 substituents independently selected from R 10 .

21. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is NR c R d .

22. The compound of claim 21 , or a pharmaceutically acceptable salt thereof, wherein R c is 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 of R c are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 ; and R d is 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 of R d are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 10 .

23. The compound of claim 21 , or a pharmaceutically acceptable salt thereof, wherein R c is H; and R d is C 1-6 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from R 10 .

24. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, 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, halo, 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)OR a1 , 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, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 .

25. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, 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, halo, CN, OR a1 , SR 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, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 .

26. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, OR a1 , 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 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 11 .

27. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, and OR a1 ; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 11 .

28. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, 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 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , NR c3 C(O)R b3 , and NR c3 C(O)OR a3 ; 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 .

29. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, 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, halo, CN, OR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , 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, 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 12 .

30. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently selected from C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, OR a3 , C(O)OR a3 ; wherein said C 1-6 alkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 12 .

31. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from methyl, bromo, fluoro, CN, ethyl, methoxy, 4-morpholinyl, 3-oxopiperazin-1-yl, 4-methylpiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, 4-ethylpiperazin-1-yl, 3-oxo-4-(2,2,2-trifluoroethyl)piperazin-1-yl, 4-(methylsulfonyl)piperazin-1-yl, piperazin-1-yl, 4-isopropylpiperazin-1-yl, 4-cyclopropyl-3-oxopiperazin-1-yl, 4-(methylsulfonyl)piperazin-1-yl, 4-bromo-phenyl, 4-cyanophenyl, 4-pyridyl, methylaminocarbonyl, isopropylaminocarbonyl, 3-hydroxypyrrolidin-1-yl, 3-methoxypiperidin-1-yl, 1-methylpiperidin-4-yl, ethylmethylamino, cyclopropyl, ethyl, 2-cyanophenyl, tetrahydro-2H-pyran-4-yl, azetidin-3-yl, hydroxyethyl, 4-methoxypiperidin-1-yl, 3-fluoropyrrolidin-1-yl, 4-methylcarbonylpiperazin-1-yl, 4-hydroxypiperidin-1-yl, 4-methoxycarbonylpiperazin-1-yl, amino, 2-hydroxypropylamino, (1-methyl-1H-pyrazol-5-yl)methylamino, and 3-cyanocyclopentylamino.

32. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from methyl, bromo, fluoro, CN, ethyl, methoxy, 4-morpholinyl, 3-oxopiperazin-1-yl, 4-methylpiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, 4-ethylpiperazin-1-yl, 3-oxo-4-(2,2,2-trifluoroethyl)piperazin-1-yl, 4-(methylsulfonyl)piperazin-1-yl, piperazin-1-yl, 4-isopropylpiperazin-1-yl, 4-cyclopropyl-3-oxopiperazin-1-yl, 4-(methylsulfonyl)piperazin-1-yl, 4-bromo-phenyl, 4-cyanophenyl, and 4-pyridyl.

33. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is 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, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, halo, OR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , NR c7 R d7 , NR c7 C(O)R b7 and NR c7 C(O)OR a7 ; 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 30 .

34. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, OR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , NR c7 R d7 , NR c7 C(O)R b7 , and NR c7 C(O)OR a7 ; 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 30 .

35. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, and OR a7 .

36. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, and halo.

37. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is H.

38. The compound of claim 1 having Formula IV:

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

39. The compound of claim 1 having Formula Vb, Formula Vc, or Formula Vd:

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

40. The compound of claim 38 , or a pharmaceutically acceptable salt thereof, wherein n is 3.

41. The compound of claim 38 , or a pharmaceutically acceptable salt thereof, wherein n is 2.

42. The compound of claim 38 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently fluoro, methyl, trifluoromethyl, CH 2 NHCH 3 , CH 2 NH(i-propyl), CH 2 -azetidinyl, CH 2 NH(CH 2 )CH 3 , or CH(CH 3 )(NHCH 3 ).

43. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, NO 2 , 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 R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NOR a )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , 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 A is C 6-10 aryl optionally substituted with 1, 2, 3 or 4 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 cycloalkyl-C 1-3 alkylene, 6-10 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 , QC(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 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 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, 6-10 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 ;

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 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(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 , 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 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 ;

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 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 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 ;

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 OR 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 30 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 a8 , SR a8 , C(O)R b8 , C(O)NR c8 R d8 , C(O)OR a8 , NR c8 R d8 , NR c8 C(O)R b8 , NR c8 C(O)OR a8 , NR c8 S(O)R b8 , NR c8 S(O) 2 R b8 , NR c8 S(O) 2 NR c8 R d8 , S(O)R b8 , S(O)NR c8 R d8 , S(O) 2 R b8 , and S(O) 2 NR c8 R d8 , 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 b is independently selected from C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 7-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl; wherein said C 2-6 alkenyl, C 2-6 alkynyl, 7-10 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 b7 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl;

44. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, NO 2 , 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 R d , NR c C(O)R b , and NR c C(O)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 ;

Cy A is C 6-10 aryl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 20 ;

R 2 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)OR a7 , NR c7 S(O)R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , and S(O) 2 NR c7 R d7 ; 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 30 ;

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, 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 c1 R d1 , NR c1 C(O)R b1 , and NR c1 C(O)OR a1 ; wherein said 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 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, halo, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , S(O)R b3 , S(O)NR c3 R d3 , 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, and 5-10 membered heteroaryl 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, 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, and C 2-6 alkynyl 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, 4-10 membered heterocycloalkyl-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 , and NR c2 C(O)OR a2 ; 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, and 4-10 membered heterocycloalkyl-C 1-3 alkylene 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, 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 , and NR c4 C(O)OR a4 ; 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 22 ;

each R 22 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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 OR d6 , NR c6 C(O)R b6 , and NR c6 C(O)OR a6 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and 5-6 membered heteroaryl are each optionally substituted with 1 substituents independently selected from R g ;

each R 30 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl;

each R a and R c 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 10 ;

each R a1 , R c1 and R d1 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, and C 3-10 cycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-10 cycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 11 ;

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

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, and C 1-6 haloalkyl;

each R b3 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, and phenyl;

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, phenyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 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;

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, and phenyl;

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;

each R b5 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl;

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;

each R b6 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl;

each R a7 , R c7 , and R d7 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 30 ;

each R b7 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 30 ;

45. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, OR a , C(O)R b , C(O)NR c R d , C(O)OR a , NR c R d , NR c C(O)R b , and NR c C(O)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 ;

Cy A is C 6-10 aryl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 20 ;

R 2 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, and OR a7 ;

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, halo, CN, OR a1 , C(O)NR c1 R d1 , and NR c1 R d1 , wherein said 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 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, halo, CN, OR a3 , C(O)OR a3 , C(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)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, and 5-10 membered heteroaryl 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, halo, and CN;

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, 4-10 membered heterocycloalkyl-C 1-3 alkylene, halo, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , 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 , and NR c2 C(O)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, and 4-10 membered heterocycloalkyl-C 1-3 alkylene 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, halo, CN, OR a4 , NR c4 R d4 , NR c4 C(O)R b4 , and NR c4 C(O)OR a4 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and 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 22 ;

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

each R a and R c is independently selected from H and C 1-6 alkyl;

each R a1 , R c1 , and R d1 is independently selected from H, C 1-6 alkyl, and C 3-10 cycloalkyl; wherein said C 1-6 alkyl and C 3-10 cycloalkyl, are each optionally substituted with 1 or 2 substituents independently selected from R 11 ;

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, and 4-10 membered heterocycloalkyl; 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 or 2 substituents independently selected from R 21 ;

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

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, and C 1-6 haloalkyl;

each R b3 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, and phenyl;

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, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1 or 2 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;

each R b4 is independently selected from C 1-6 alkyl;

each R a6 is independently selected from H and C 1-6 alkyl;

each 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;

each R b6 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl;

each R a7 is independently selected from H and C 1-6 alkyl; and

each R g is independently selected from C 1-6 alkyl.

46. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from C 2-6 alkenyl, C(O)NR c R d , NR c R d , and NR c C(O)R b ; wherein said C 2-6 alkenyl is optionally substituted with 1 independently selected from R 10 ;

Cy A is C 6-10 aryl optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 20 ;

R 2 is H, halo, or OR a7 ;

each R 10 is independently selected from C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, OR a1 , C(O)NR c1 R d1 , and NR c1 R d1 , wherein said C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 11 ;

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

each R 12 is C 1-6 alkyl, halo, or CN;

each R 20 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 4-10 membered heterocycloalkyl-C 1-3 alkylene, halo, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , 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 , and NR c2 C(O)NR c2 R d2 ; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and 4-10 membered heterocycloalkyl-C 1-3 alkylene are each optionally substituted with 1 or 2 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 C 3-7 cycloalkyl ring; and wherein the fused C 3-7 cycloalkyl ring is optionally substituted with 1 or 2 substituents independently selected from R 21 ;

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

each R 22 is independently selected from C 1-6 alkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, CN, OR a6 and NR c6 R d6 , wherein said C 1-6 alkyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R g ;

each R a and R c is H;

each R d is independently selected from C 1-6 alkyl, C 6-10 aryl, and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 10 ;

each R b is independently selected from 7-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl; wherein said 7-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 10 ;

each R a1 , R c1 and R d1 is independently selected from H, C 1-6 alkyl, and C 3-10 cycloalkyl; wherein said C 1-6 alkyl and C 3-10 cycloalkyl, are each optionally substituted with 1 or 2 substituents independently selected from R 11 ;

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

each R a3 is independently selected from H and C 1-6 alkyl;

each R b3 is C 1-6 alkyl;

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

each R b4 is independently selected from C 1-6 alkyl;

each R a6 is independently selected from H and C 1-6 alkyl;

each R c6 and R d6 is H;

each R a7 is independently selected from H and C 1-6 alkyl; and

each R g is independently selected from C 1-6 alkyl.

47. The compound of claim 1 selected from

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)benzamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-methylbenzamide;

4-Bromo-N-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)benzamide;

3-Bromo-N-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)benzamide;

4-Fluoro-N-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)benzamide;

3-Fluoro-N-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)benzamide;

3-Cyano-N-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)benzamide;

4-Ethyl-N-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)benzamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-3-methoxybenzamide;

4-Fluoro-N-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-3-methylbenzamide;

3,5-Difluoro-N-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)benzamide;

3,4-Difluoro-N-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)benzamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)benzo[d][1,3]dioxole-5-carboxamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1-methyl-1H-pyrazole-4-carboxamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1-methyl-1H-pyrazole-3-carboxamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-3-morpholinobenzamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-3-(3-oxopiperazin-1-yl)benzamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-3-(4-methylpiperazin-1-yl)benzamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-3-(4-methyl-3-oxopiperazin-1-yl)benzamide;

3-(4-Ethylpiperazin-1-yl)-N-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)benzamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-3-(3-oxo-4-(2,2,2-trifluoroethyl) piperazin-1-yl)benzamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-3-(4-(methylsulfonyl) piperazin-1-yl)benzamide;

N-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-3-(piperazin-1-yl)benzamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-morpholinobenzamide

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(3-oxopiperazin-1-yl)benzamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)benzamide;

N-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(4-methyl-3-oxopiperazin-1-yl)benzamide;

4-(4-Ethylpiperazin-1-yl)-N-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)benzamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(3-oxo-4-(2,2,2-trifluoroethyl) piperazin-1-yl)benzamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(4-isopropylpiperazin-1-yl)benzamide;

4-(4-Cyclopropyl-3-oxopiperazin-1-yl)-N-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)benzamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(4-(methylsulfonyl) piperazin-1-yl)benzamide;

N-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(piperazin-1-yl)benzamide;

5-(2-Fluoro-6-methoxyphenyl)-N-(4-(4-methylpiperazin-1-yl)benzyl)-1H-pyrazolo[3,4-c]pyridin-3-amine;

5-(2-Fuoro-6-methoxyphenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridine-3-carboxamide;

5-(2-Fluoro-6-methoxyphenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; and

N-(4-(4-Ethylpiperazin-1-yl)phenyl)-5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridine-3-carboxamide;

or a pharmaceutically acceptable salt thereof.

48. The compound of claim 1 selected from:

3-(4-Bromostyryl)-5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridine,

N-(5-(2,6-Difluoro-4-((isopropylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)benzamide,

N-(5-(2,6-Difluoro-4-(pyrrolidin-1-ylmethyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)benzamide,

N-(5-(4-(Azetidin-1-ylmethyl)-2,6-difluorophenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)benzamide,

N-(5-(2,6-Difluoro-4-((3-methoxyazetidin-1-yl)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)benzamide,

N-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1-methyl-1H-pyrazole-4-carboxamide,

N-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-3-(4-methylpiperazin-1-yl)benzamide,

N-(5-(2,6-Difluoro-4-((isopropylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-3-methoxybenzamide,

Methyl 4-(4-(5-(2,6-difluoro-4-((isopropylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-ylcarbamoyl)-3-fluorophenyl)piperazine-1-carboxylate,

N-(5-(2,6-Difluoro-4-((isopropylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-2-methoxy-4-(4-methylpiperazin-1-yl)benzamide,

N-(5-(2,6-Difluoro-4-((isopropylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-2-fluoro-3-(4-methylpiperazin-1-yl)benzamide,

N-(5-(2,6-Difluoro-4-((isopropylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-fluoro-3-(4-methylpiperazin-1-yl)benzamide,

N-(5-(2-Fluoro-6-methylphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)benzamide,

N-(5-(2-Fluoro-6-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)benzamide,

N-(5-(4-((Ethylamino)methyl)-2-fluoro-6-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)benzamide,

5-(2,6-Difluoro-4-((isopropylamino)methyl)phenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridine-3-carboxamide,

N-(5-(2,6-Difluoro-4-(2-(pyrrolidin-1-yl)acetamido)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)benzamide,

2-Amino-N-(5-(2-fluoro-6-methylphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)benzamide,

N-(5-(2-Fluoro-6-methylphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-2-(2-hydroxypropylamino)-4-(4-methylpiperazin-1-yl)benzamide,

N-(5-(2-Fluoro-6-methylphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-2-((1-methyl-1H-pyrazol-5-yl)methylamino)-4-(4-methylpiperazin-1-yl)benzamide, and

2-(3-Cyanocyclopentylamino)-N-(5-(2-fluoro-6-methylphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)benzamide, or a pharmaceutically acceptable salt thereof.

49. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 25, 2023

From: VECHORKIN, OLEG; PAN, JUN; LIU, KAI; SOKOLSKY, ALEXANDER; WANG, ANLAI; YE, HAI FEN; YE, QINDA; YAO, WENQING

To: INCYTE CORPORATION

Reel/Frame 065013/0795 →

Continuity (6)

Continuation 17143567 · Jan 7, 2021

Continuation 16545778 · Aug 20, 2019

Continuation 16209856 · Dec 4, 2018

Continuation 15698788 · Sep 8, 2017

Provisional Application 62385584 · Sep 9, 2016

Related Publication 20240287059A1 · Aug 29, 2024

References Cited (400)

US 5250534A · Bell et al. · 1993 [cited by applicant]

US 6200980B1 · Piazza et al. · 2001 [cited by applicant]

US 6333330B1 · Bunnage et al. · 2001 [cited by applicant]

US 6458951B2 · Bunnage et al. · 2002 [cited by applicant]

US 6512002B2 · Lee et al. · 2003 [cited by applicant]

US 6670366B1 · Bunnage et al. · 2003 [cited by applicant]

US 6743799B2 · Westbrook et al. · 2004 [cited by applicant]

US 6756373B1 · Allerton et al. · 2004 [cited by applicant]

US 6770645B2 · Denton et al. · 2004 [cited by applicant]

US 6784185B2 · Allerton et al. · 2004 [cited by applicant]

US 6916927B2 · Bunnage et al. · 2005 [cited by applicant]

US 7105532B2 · Rawlings · 2006 [cited by examiner]

US 7166293B2 · Teng et al. · 2007 [cited by applicant]

US 7259165B2 · Bernotas et al. · 2007 [cited by applicant]

US 7345178B2 · Nunes et al. · 2008 [cited by applicant]

US 7429609B2 · Ohi et al. · 2008 [cited by applicant]

US 7576087B2 · Bernotas et al. · 2009 [cited by applicant]

US 7919487B2 · Sun et al. · 2011 [cited by applicant]

US 7968719B2 · Zoller et al. · 2011 [cited by applicant]

US 8106190B2 · Kuramochi et al. · 2012 [cited by applicant]

US 8450335B2 · Singh et al. · 2013 [cited by applicant]

US 8546403B2 · Whitten et al. · 2013 [cited by applicant]

US 8637507B2 · Zhou et al. · 2014 [cited by applicant]

US 8722691B2 · He et al. · 2014 [cited by applicant]

US 8987273B2 · Rehwinkel et al. · 2015 [cited by applicant]

US 9090593B2 · Wang et al. · 2015 [cited by applicant]

US 9260425B2 · Do et al. · 2016 [cited by applicant]

US 9284319B2 · Eis et al. · 2016 [cited by applicant]

US 9320737B2 · Eis et al. · 2016 [cited by applicant]

US 9718818B2 · DeMong et al. · 2017 [cited by applicant]

US 9730929B2 · Eis et al. · 2017 [cited by applicant]

US 10266530B2 · Vechorkin et al. · 2019 [cited by applicant]

US 10280164B2 · Ye et al. · 2019 [cited by applicant]

US 10435405B2 · Vechorkin et al. · 2019 [cited by applicant]

US 10722495B2 · Vechorkin et al. · 2020 [cited by applicant]

US 10745388B2 · Vechorkin et al. · 2020 [cited by applicant]

US 10752635B2 · Sokolsky et al. · 2020 [cited by applicant]

US 10800761B2 · Vechorkin et al. · 2020 [cited by applicant]

US 10899755B2 · Hummel et al. · 2021 [cited by applicant]

US 10934288B2 · Vechorkin et al. · 2021 [cited by applicant]

US 11014929B2 · Vechorkin et al. · 2021 [cited by applicant]

US 11066394B2 · Jia et al. · 2021 [cited by applicant]

US 11242343B2 · Liu et al. · 2022 [cited by applicant]

US 11299473B2 · Hummel et al. · 2022 [cited by applicant]

US 11406624B2 · Sokolsky et al. · 2022 [cited by applicant]

US 11492354B2 · Sokolsky et al. · 2022 [cited by applicant]

US 11542265B2 · Vechorkin et al. · 2023 [cited by applicant]

US 11731958B2 · Vechorkin et al. · 2023 [cited by applicant]

US 11787784B2 · Jia et al. · 2023 [cited by applicant]

US 11795166B2 · Vechorkin et al. · 2023 [cited by applicant]

US 11866426B2 · Hummel et al. · 2024 [cited by applicant]

US 20020013327A1 · Lee et al. · 2002 [cited by applicant]

US 20030162782A1 · Grossman et al. · 2003 [cited by applicant]

US 20030186996A1 · Teng et al. · 2003 [cited by applicant]

US 20040063730A1 · Eggenweiler et al. · 2004 [cited by applicant]

US 20040077681A1 · Rawlings et al. · 2004 [cited by applicant]

US 20040147546A1 · Tanaka et al. · 2004 [cited by applicant]

US 20040157866A1 · Takasugi et al. · 2004 [cited by applicant]

US 20040167030A1 · Bernotas et al. · 2004 [cited by applicant]

US 20040204417A1 · Perez et al. · 2004 [cited by applicant]

US 20050070557A1 · Fryburg et al. · 2005 [cited by applicant]

US 20050075795A1 · Pandit · 2005 [cited by applicant]

US 20050119278A1 · Teng et al. · 2005 [cited by applicant]

US 20050137226A1 · Ji et al. · 2005 [cited by applicant]

US 20050208582A1 · Ohi et al. · 2005 [cited by applicant]

US 20050261339A1 · Ohi et al. · 2005 [cited by applicant]

US 20060106032A1 · Kuo et al. · 2006 [cited by applicant]

US 20070087988A1 · Sawasdikosol et al. · 2007 [cited by applicant]

US 20070161673A1 · Barker et al. · 2007 [cited by applicant]

US 20070185152A1 · Yamashita et al. · 2007 [cited by applicant]

US 20070270412A1 · Bell et al. · 2007 [cited by applicant]

US 20080280891A1 · Kelly et al. · 2008 [cited by applicant]

US 20100035891A1 · Bunnage et al. · 2010 [cited by applicant]

US 20100087464A1 · Mi et al. · 2010 [cited by applicant]

US 20100216798A1 · Nakai et al. · 2010 [cited by applicant]

US 20120129852A1 · Duan et al. · 2012 [cited by applicant]

US 20120225869A1 · Liu et al. · 2012 [cited by applicant]

US 20120295884A1 · Altmann et al. · 2012 [cited by applicant]

US 20130039906A1 · Do et al. · 2013 [cited by applicant]

US 20130040949A1 · Gray et al. · 2013 [cited by applicant]

US 20130281433A1 · Babaoglu et al. · 2013 [cited by applicant]

US 20140225073A1 · Lee et al. · 2014 [cited by applicant]

US 20140249135A1 · Burger et al. · 2014 [cited by applicant]

US 20140288045A1 · Ren et al. · 2014 [cited by applicant]

US 20140288069A1 · Eis et al. · 2014 [cited by applicant]

US 20140350017A1 · Williams et al. · 2014 [cited by applicant]

US 20140364605A1 · Li et al. · 2014 [cited by applicant]

US 20150038485A1 · Eis et al. · 2015 [cited by applicant]

US 20150191462A1 · Hommel et al. · 2015 [cited by applicant]

US 20150239868A1 · Pais et al. · 2015 [cited by applicant]

US 20150239889A1 · Nakajima et al. · 2015 [cited by applicant]

US 20150243908A1 · Lee et al. · 2015 [cited by applicant]

US 20150274639A1 · Williams et al. · 2015 [cited by applicant]

US 20150328188A1 · Orlemans et al. · 2015 [cited by applicant]

US 20160013427A1 · Kim et al. · 2016 [cited by applicant]

US 20160046648A1 · Petrukhin et al. · 2016 [cited by applicant]

US 20160068529A1 · Kc et al. · 2016 [cited by applicant]

US 20160068547A1 · Kc et al. · 2016 [cited by applicant]

US 20160068548A1 · Kc et al. · 2016 [cited by applicant]

US 20160068551A1 · Kc et al. · 2016 [cited by applicant]

US 20160200722A1 · DeMong et al. · 2016 [cited by applicant]

US 20180072718A1 · Liu et al. · 2018 [cited by applicant]

US 20180072719A1 · Ye et al. · 2018 [cited by applicant]

US 20180072720A1 · Vechorkin et al. · 2018 [cited by applicant]

US 20180072741A1 · Vechorkin et al. · 2018 [cited by applicant]

US 20180228786A1 · Sokolsky · 2018 [cited by applicant]

US 20190076401A1 · Vechorkin et al. · 2019 [cited by applicant]

US 20190106419A1 · Vechorkin et al. · 2019 [cited by applicant]

US 20190256500A1 · Vechorkin et al. · 2019 [cited by applicant]

US 20190256520A1 · Sokolsky · 2019 [cited by applicant]

US 20190315717A1 · Hummel et al. · 2019 [cited by applicant]

US 20190315743A1 · Liu et al. · 2019 [cited by applicant]

US 20190343814A1 · Sokolsky · 2019 [cited by applicant]

US 20190382380A1 · Vechorkin et al. · 2019 [cited by applicant]

US 20200048241A1 · Hummel et al. · 2020 [cited by applicant]

US 20200087301A1 · Vechorkin et al. · 2020 [cited by applicant]

US 20200172545A1 · Vechorkin et al. · 2020 [cited by applicant]

US 20200283434A1 · Liu et al. · 2020 [cited by applicant]

US 20210002288A1 · Sokolsky · 2021 [cited by applicant]

US 20210040071A1 · Jia et al. · 2021 [cited by applicant]

US 20210094934A1 · Vechorkin et al. · 2021 [cited by applicant]

US 20210171518A1 · Hummel et al. · 2021 [cited by applicant]

US 20210371425A1 · Vechorkin et al. · 2021 [cited by applicant]

US 20210380581A1 · Vechorkin et al. · 2021 [cited by applicant]

US 20220162195A1 · Jia et al. · 2022 [cited by applicant]

US 20220227752A1 · Liu et al. · 2022 [cited by applicant]

US 20240150326A1 · Vechorkin et al. · 2024 [cited by applicant]

US 20240383889A1 · Liu et al. · 2024 [cited by applicant]

CN 102206172 · 2011 [cited by applicant]

CN 102503959 · 2012 [cited by applicant]

CN 102516263 · 2012 [cited by applicant]

CN 103570709 · 2014 [cited by applicant]

DE 102004054666 · 2006 [cited by applicant]

EP 2543372 · 2013 [cited by applicant]

EP 2824099 · 2015 [cited by applicant]

IN 187433 · 2002 [cited by applicant]

JP H03287584 · 1991 [cited by applicant]

JP 2000038350 · 2000 [cited by applicant]

JP 2007055940 · 2007 [cited by applicant]

JP 2010111624 · 2010 [cited by applicant]

JP 2011246389 · 2011 [cited by applicant]

KR 963644 · 1996 [cited by applicant]

KR 20140019055 · 2014 [cited by applicant]

KR 20180015255 · 2018 [cited by applicant]

MX 9910322 · 2003 [cited by applicant]

MY 146643 · 2012 [cited by applicant]

WO WO1989008263 · 1989 [cited by applicant]

WO WO2000043394 · 2000 [cited by applicant]

WO WO2001019827 · 2001 [cited by applicant]

WO WO2001019828 · 2001 [cited by applicant]

WO WO2001021576 · 2001 [cited by applicant]

WO WO2001046124 · 2001 [cited by applicant]

WO WO2002000196 · 2002 [cited by applicant]

WO WO2002016348 · 2002 [cited by applicant]

WO WO2002019975 · 2002 [cited by applicant]

WO WO2002050073 · 2002 [cited by applicant]

WO WO2002090347 · 2002 [cited by applicant]

WO WO2003037432 · 2003 [cited by applicant]

WO WO2003049681 · 2003 [cited by applicant]

WO WO2004072069 · 2004 [cited by applicant]

WO WO2004096810 · 2004 [cited by applicant]

WO WO2004108133 · 2004 [cited by applicant]

WO WO2005004799 · 2005 [cited by applicant]

WO WO2005011681 · 2005 [cited by applicant]

WO WO2005028475 · 2005 [cited by applicant]

WO WO2005051906 · 2005 [cited by applicant]

WO WO2005066167 · 2005 [cited by applicant]

WO WO2005073199 · 2005 [cited by applicant]

WO WO2005073232 · 2005 [cited by applicant]

WO WO2003101968 · 2005 [cited by applicant]

WO WO2005085227 · 2005 [cited by applicant]

WO WO2005085248 · 2005 [cited by applicant]

WO WO2005085249 · 2005 [cited by applicant]

WO WO2006013095 · 2006 [cited by applicant]

WO WO2006028958 · 2006 [cited by applicant]

WO WO2006038001 · 2006 [cited by applicant]

WO WO2006045010 · 2006 [cited by applicant]

WO WO2006050097 · 2006 [cited by applicant]

WO WO2006053109 · 2006 [cited by applicant]

WO WO2006053121 · 2006 [cited by applicant]

WO WO2006053227 · 2006 [cited by applicant]

WO WO2006074428 · 2006 [cited by applicant]

WO WO2006105289 · 2006 [cited by applicant]

WO WO2006128172 · 2006 [cited by applicant]

WO WO2007019344 · 2007 [cited by applicant]

WO WO2007019345 · 2007 [cited by applicant]

WO WO2007019346 · 2007 [cited by applicant]

WO WO2007019417 · 2007 [cited by applicant]

WO WO2007020050 · 2007 [cited by applicant]

WO WO2007023110 · 2007 [cited by applicant]

WO WO2007023111 · 2007 [cited by applicant]

WO WO2007023114 · 2007 [cited by applicant]

WO WO2007030582 · 2007 [cited by applicant]

WO WO2007056280 · 2007 [cited by applicant]

WO WO2007063925 · 2007 [cited by applicant]

WO WO2007065924 · 2007 [cited by applicant]

WO WO2007080382 · 2007 [cited by applicant]

WO WO2007093402 · 2007 [cited by applicant]

WO WO2007112093 · 2007 [cited by applicant]

WO WO2007114848 · 2007 [cited by applicant]

WO WO2007137030 · 2007 [cited by applicant]

WO WO2008008059 · 2008 [cited by applicant]

WO WO2008008539 · 2008 [cited by applicant]

WO WO2008012027 · 2008 [cited by applicant]

WO WO2008045627 · 2008 [cited by applicant]

WO WO2008070313 · 2008 [cited by applicant]

WO WO2008089307 · 2008 [cited by applicant]

WO WO2008089310 · 2008 [cited by applicant]

WO WO2008113856 · 2008 [cited by applicant]

WO WO2009019167 · 2009 [cited by applicant]

WO WO2009024341 · 2009 [cited by applicant]

WO WO2009032651 · 2009 [cited by applicant]

WO WO2009038784 · 2009 [cited by applicant]

WO WO2009058348 · 2009 [cited by applicant]

WO WO2009100130 · 2009 [cited by applicant]

WO WO2009139834 · 2009 [cited by applicant]

WO WO2009152356 · 2009 [cited by applicant]

WO WO2010029300 · 2010 [cited by applicant]

WO WO2010035217 · 2010 [cited by applicant]

WO WO2010035219 · 2010 [cited by applicant]

WO WO2010035221 · 2010 [cited by applicant]

WO WO2010046780 · 2010 [cited by applicant]

WO WO2010080503 · 2010 [cited by applicant]

WO WO2010104306 · 2010 [cited by applicant]

WO WO2010107765 · 2010 [cited by applicant]

WO WO2010107768 · 2010 [cited by applicant]

WO WO2010111624 · 2010 [cited by applicant]

WO WO2010118367 · 2010 [cited by applicant]

WO WO2011019780 · 2011 [cited by applicant]

WO WO2011031628 · 2011 [cited by applicant]

WO WO2011050245 · 2011 [cited by applicant]

WO WO2011051535 · 2011 [cited by applicant]

WO WO2011062253 · 2011 [cited by applicant]

WO WO2011078143 · 2011 [cited by applicant]

WO WO2011082400 · 2011 [cited by applicant]

WO WO2011082488 · 2011 [cited by applicant]

WO WO2011107186 · 2011 [cited by applicant]

WO WO2011133920 · 2011 [cited by applicant]

WO WO2011139489 · 2011 [cited by applicant]

WO WO2011141756 · 2011 [cited by applicant]

WO WO2011147765 · 2011 [cited by applicant]

WO WO2011153553 · 2011 [cited by applicant]

WO WO2011157653 · 2011 [cited by applicant]

WO WO2011158108 · 2011 [cited by applicant]

WO WO2012048058 · 2012 [cited by applicant]

WO WO2012049277 · 2012 [cited by applicant]

WO WO2012078777 · 2012 [cited by applicant]

WO WO2012080376 · 2012 [cited by applicant]

WO WO2012109263 · 2012 [cited by applicant]

WO WO2012130780 · 2012 [cited by applicant]

WO WO2012141487 · 2012 [cited by applicant]

WO WO2012143144 · 2012 [cited by applicant]

WO WO2012158810 · 2012 [cited by applicant]

WO WO2012163959 · 2012 [cited by applicant]

WO WO2013007708 · 2013 [cited by applicant]

WO WO2013021276 · 2013 [cited by applicant]

WO WO2013024002 · 2013 [cited by applicant]

WO WO2013024011 · 2013 [cited by applicant]

WO WO2013042137 · 2013 [cited by applicant]

WO WO2013064445 · 2013 [cited by applicant]

WO WO2013123215 · 2013 [cited by applicant]

WO WO2013130890 · 2013 [cited by applicant]

WO WO2013146942 · 2013 [cited by applicant]

WO WO2014003405 · 2014 [cited by applicant]

WO WO2014024125 · 2014 [cited by applicant]

WO WO2014047616 · 2014 [cited by applicant]

WO WO2014055955 · 2014 [cited by applicant]

WO WO2014151616 · 2014 [cited by applicant]

WO WO2015026683 · 2015 [cited by applicant]

WO WO2015037965 · 2015 [cited by applicant]

WO WO2015038503 · 2015 [cited by applicant]

WO WO2015058163 · 2015 [cited by applicant]

WO WO2015061247 · 2015 [cited by applicant]

WO WO2015089327 · 2015 [cited by applicant]

WO WO2015089479 · 2015 [cited by applicant]

WO WO2015090235 · 2015 [cited by applicant]

WO WO2015091426 · 2015 [cited by applicant]

WO WO2015104662 · 2015 [cited by applicant]

WO WO2015117718 · 2015 [cited by applicant]

WO WO2015164956 · 2015 [cited by applicant]

WO WO2015192939 · 2015 [cited by applicant]

WO WO2015193506 · 2015 [cited by applicant]

WO WO2015193846 · 2015 [cited by applicant]

WO WO2015200682 · 2015 [cited by applicant]

WO WO2016040180 · 2016 [cited by applicant]

WO WO2016040181 · 2016 [cited by applicant]

WO WO2016041618 · 2016 [cited by applicant]

WO WO2020151742 · 2016 [cited by applicant]

WO WO2016057500 · 2016 [cited by applicant]

WO WO2016083433 · 2016 [cited by applicant]

WO WO2016090300 · 2016 [cited by applicant]

WO WO2016124304 · 2016 [cited by applicant]

WO WO2016144351 · 2016 [cited by applicant]

WO WO2016144702 · 2016 [cited by applicant]

WO WO2016164285 · 2016 [cited by applicant]

WO WO2016174183 · 2016 [cited by applicant]

WO WO2016205942 · 2016 [cited by applicant]

WO WO2017009798 · 2017 [cited by applicant]

WO WO2017009806 · 2017 [cited by applicant]

WO WO2017023894 · 2017 [cited by applicant]

WO WO2017023972 · 2017 [cited by applicant]

WO WO2017027400 · 2017 [cited by applicant]

WO WO2017045955 · 2017 [cited by applicant]

WO WO2017058915 · 2017 [cited by applicant]

WO WO2017108744 · 2017 [cited by applicant]

WO WO2017120429 · 2017 [cited by applicant]

WO WO2018019204 · 2018 [cited by applicant]

WO WO2019164846 · 2019 [cited by applicant]

WO WO2019207463 · 2021 [cited by applicant]

WO WO2019211451 · 2021 [cited by applicant]

WO WO2019219517 · 2021 [cited by applicant]

ZA 2003005330 · 2003 [cited by applicant]

Alzabin et al., “Hematopoietic progenitor kinase 1 is a critical component of prostaglandin E2-mediated suppression of the anti-tumor immune response,” Cancer Immunol Immunother, 2010, 59(3):419-429. [cited by applicant]

Alzabin et al., “Hematopoietic progenitor kinase 1 is a negative regulator of dendritic cell activation,” J Immunol, 2009, 182(10):6187-6194. [cited by applicant]

Anonymous, “Crystalline APX,” IP.com #IPCOM000233879, Dec. 25, 2013, 3 pages. [cited by applicant]

Anonymous, “Crystalline ethyl 1-(4-methoxyphenyl)-6-(4-nitrophenyl)-7-oxo-,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate,” IP.com #IPCOM000233229D, Dec. 3, 2019, 4 pages. [cited by applicant]

Antoine et al., “Efficient synthesis of novel disubstituted pyrido[3,4-b]pyrazines for the design of protein kinase inhibitors,” Med Chem Common., 2016, 6:224-229. [cited by applicant]

Antunes et al., “In silico prediction of novel phosphodiesterase type-5 inhibitors derived from Sildenafil, Vardenafil and Tadalafil,” Bioorg. Med. Chem., Aug. 15, 2008, 16(16):7599-7606. [cited by applicant]

Atzrodt et al., “The Renaissance of H/D Exchange,” Angew. Chem. Int. Ed., 2007, 7744-7765. [cited by applicant]

Australian Office Action in Australian Application No. 2017322427, dated Dec. 16, 2020, 5 pages. [cited by applicant]

Bae et al., “Cancer Targeted Drug Delivery,” Springer: New York, 2013, p. v. [cited by applicant]

Ballell et al., “Fueling Open-Source Drug Discovery: 177 Small-Molecule Leads against Tuberculosis,” ChemMedChem., 2013, 8(2):313-321. [cited by applicant]

Balog et al., “The synthesis and evaluation of [2.2.1]-bicycloazahydantoins as androgen receptor antagonists,” Bioorg. Med. Chem. Lett., Dec. 20, 2004, 14(24):6107-6111. [cited by applicant]

Batliwalla et al., “Microarray analyses of peripheral blood cells identifies unique gene expression signature in psoriatic arthritis,” Mol Med, 2005, 11(1-12):21-29. [cited by applicant]

Benz, “The Jeremiah Metzger Lecture Cancer in the Twenty-First Century: An Inside View from an Outsider,” Trans. Am. Clin. Climatol. Assoc., 2017, 128:275-297. [cited by applicant]

Berge et al., “Pharmaceutical Salts,” J. Pharm. Sci., 1977, 66(1):1-19. [cited by applicant]

Blom et al., “Optimizing Preparative LC-MS Configurations and Methods for Parallel Synthesis Purification,” J. Combi. Chem., 2003, 5:670. [cited by applicant]

Blom et al., “Preparative LC-MS Purification: Improved Compound Specific Method Optimization,” J. Combi. Chem., 2004, 6:874-883. [cited by applicant]

Blom et al., “Two-Pump at Column Dilution Configuration for Preparative LC-MS,” J. Combi. Chem., 2002, 4: 295. [cited by applicant]

Boomer et al., “Functional Interactions of HPK1 With Adaptor Proteins” Journal of Cellular Biochemistry, 2005, 95:34-44. [cited by applicant]

Brioche et al., “Chiral Phosphoric Acid-Catalyzed Enantioselective Three-Component Aza-Diels-Alder Reactions of Aminopyrroles and Aminopyrazoles,” Advanced Synthesis & Catalysis, 2014, 356(8):1719-1724. [cited by applicant]

CAS Registry No. 439290-60-5, “1-Piperidinebutanamide, N-(5-phenyl-1H-pyrazolo[3,4-c ]pyridin-3-yl)-(9CI, ACI),” published on Jul. 18, 2002, retreived on Jan. 23, 2025, retrieved from CAS SciFinder database, 3 pages. [cited by applicant]

Chessari et al., “Fragment-Based Drug Discovery Targeting Inhibitor of Apoptosis Proteins: Discovery of a Non-Alanine Lead Series with Dual Activity Against cIAP1 and XIAP,” J. Med. Chem., Jul. 18, 2015, 58(16):6574-658… [cited by applicant]

Cheung et al., “A Parallel Synthesis Approach to the Identification of Novel Diheteroarylamide-Based Compounds Blocking HIV Replication: Potential Inhibitors of HIV-1 Pre-mRNA Alternative Splicing,” J Med Chem., Mar. 10… [cited by applicant]

Chilean Office Action in Chilean Application No. 2146-2020, dated Oct. 10, 2021, 18 pages. [cited by applicant]

Chinchilla and Najera, “Recent advances in Sonogashira reactions,” Chem. Soc. Rev., 2011, 40: 5084-5121. [cited by applicant]

Chinese Office Action in Chinese Application No. 201780068722.2, dated Jul. 15, 2021, 13 pages. [cited by applicant]

Chinese Office Action in Chinese Application No. 202211268174.7, dated Apr. 25, 2024, 16 pages (with English Translation). [cited by applicant]

Chinese Office Action in Chinese Application No. 2022112681747, dated Nov. 7, 2024, 10 pages (with English Translation). [cited by applicant]

Choi et al., “In vitro metabolism of a novel phosphodiesterase-5 inhibitor DA-8159 in rat liver preparations using liquid chromatography/electrospray mass spectrometry,” Biomed. Chromatogr., Sep. 2002, 16(6):395-399. [cited by applicant]

Colombian Office Action in Colombian Application No. NC2020/0011530, dated Oct. 26, 2022, 19 pages (with English translation). [cited by applicant]

Cordovilla et al., “The Stille Reaction, 38 Years Later,” ACS Catalysis, 2015, 5: 3040-3053. [cited by applicant]

Devegowda et al., “Novel 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-one derivatives as potential anti-cancer agents,” Bioorg. Med. Chem. Lett., Mar. 1, 2010, 20(5):1630-1633. [cited by applicant]

Di Bartolo et al., “A novel pathway down-modulating T cell activation involves HPK-1-dependent recruitment of 14-3-3 proteins on SLP-76,” J. Exp. Med., Mar. 2007, 204(3): 681-691. [cited by applicant]

Dolgin, “Lung Cancer Outlook,” Nature, Nov. 19, 2020, 587:S16-S17. [cited by applicant]

Dong et al., “Pharmacophore identification, virtual screening and biological evaluation of prenylated flavonoids derivatives as PKB/Akt1 inhibitors,” Eur. J. Med. Chem., Dec. 2011, 46(12):5949-5958. [cited by applicant]

Dong et al., “QSAR study of Akt/protein kinase B (PKB) inhibitors using support vector machine,” Eur. J. Med. Chem., Oct. 2009, 44(10):4090-4097. [cited by applicant]

Dornow et al., “Syntheses of nitrogen-containing heterocycles. XXXVIII. Preparation and reaction of several substituted 3-nitropyridines,” Chemische Berichte, 1966, 99(1):244-253 (Machine Translation). [cited by applicant]

Dumestre-Toulet et al., “Last performance with Viagra: post-mortem identification of sildenafil and its metabolites in biological specimens including hair sample,” Forensic Sci Int., Mar. 28, 2002, 126(1):71-76. [cited by applicant]

Edmondson et al., “Aminopiperidine-fused imidazoles as dipeptidyl peptidase-IV inhibitors,” Bioorg. Med. Chem. Lett., Aug. 2009, 19(15):4097-4101. [cited by applicant]

El Sayed et al., “New route for the preparation of pyrazolo[4,3-c]pyridines,” Bulletin of the Chemical Society of Japan (1973), 46(6), 1801-1803. [cited by applicant]

El-Aziz et al., “Synthesis and in vitro anti-breast cancer activity of some novel 1,4-dihydropyridine derivatives,” Int J of Pharm Pharma Sci., 2013, 5(Suppl. 3):183-189. [cited by applicant]

Elgemeie et al., “A new general method for substituted 4-alkylthio-N-arylsulfonylamino-2-pyridones: Reaction of ketene-S,S-acetals with arylsulfonylhydrazides,” Phosphorus, Sulfur and Silicon and the Related Elements, 2… [cited by applicant]

Elgemeie et al., “Novel N-Substituted Amino-4-methylsulfanyl-2-pyridones and Deazapurine Analogues from Ketene Dithioacetals,” J Chem Res., 1998, 3:164-165. [cited by applicant]

Elgemeie et al., “Novel Nucleoside Analogues: First Synthesis of Pyridine-4-Thioglycosides and Their Cytotoxic Evaluation,” Nucleosides, Nucleotides and Nucleic Acids, Jun. 27, 2015, 34:659-673. [cited by applicant]

Elgemeie et al., “Novel synthesis of N-aroylaminated pyridones via reaction of ketene dithioacetals with cyanoaceto-N-aroylhydrazides,” Synth Comm., 2003, 33(2):253-258. [cited by applicant]

Elgemeie et al., “Synthesis of Novel Derivatives of 4-Methylthio-N-Aryl-2-Pyridone and Deazapurine Analogues: The Reaction of Ketene Dithioacetals with Substituted Acetanilides,” Phosphorus, Sulfur and Silicon, 2000, 16… [cited by applicant]

Erian, “2-Aryl-1,1-dicyano-3-phenylsulfonylpropenes in heterocyclic synthesis. A synthetic strategy towards heterocyclic sulfone,” Monatshefte fuer Chemie, Oct. 1998, 129(10):1049-1056. [cited by applicant]

Eurasian Office Action in Eurasian Application No. 201990665, Feb. 17, 2020, 5 pages. [cited by applicant]

Eurasian Office Action in Eurasian Application No. 202091983, dated Nov. 29, 2021, 4 pages. [cited by applicant]

Extended European Search Report in European Application No. 22177485.4, dated Dec. 19, 2022, 8 pages. [cited by applicant]

Figueiredo et al., “A chemometric study of phosphodiesterase 5 inhibitors,” J Mol Graph Model., Jan. 2006, 24(4):227-232. [cited by applicant]

Gao, “Slidenafil” Handbook of Metabolic Pathways of Xenobiotics, 2014, 5:2151-2154. [cited by applicant]

Garson et al., “Models of ovarian cancer—Are we there yet?” Molecular and Cellular Endocrinology, Jul. 2005, 239(1-2):15-26. [cited by applicant]

Gerratana et al., “Do platinum salts fit all triple negative breast cancers?”Cancer Treatment Reviews, Jul. 2016, 48:34-41. [cited by applicant]

Goodarzi et al., “Feature Selection and Linear/Nonlinear Regression Methods for the Accurate Prediction of Glycogen Synthase Kinase-3β Inhibitory Activities,” J. Chem. Inf. Model, 2009, 49(4):824-832. [cited by applicant]

Haas et al., “Recent Developments in Negishi Cross-Coupling Reactions,” ACS Catalysis, 2016, 6: 1540-1552. [cited by applicant]

Haning et al., “Comparison of different heterocyclic scaffolds as substrate analog PDE5 inhibitors,” Sep. 1, 2005, 15(17):3900-3907. [cited by applicant]

Hanson, “Diterpenoids of Terrestrial Origin”, National Product Reports, 2016, 33:1227-1238. [cited by applicant]

Hayat, “Autophagy: Cancer, other Pathologies, Inflammation, Immunity, Infection, and Aging,” Academic Press: San Diego, 2015, p. xxi. [cited by applicant]

He et al., “Predicting the Genotoxicity of Polycyclic Aromatic Compounds from Molecular Structure with Different Classifiers,” Chemical Research in Toxicology (2003), 16(12):1567-1580. [cited by applicant]

Ho et al., “Discovery of 4-phenyl-2-phenylaminopyridine based TNIK inhibitors,” Boorg Med Chem Lett, 2013, 23(2):569-573. [cited by applicant]

Howard et al., “Identification of potent phosphodiesterase inhibitors that demonstrate cyclic nucleotide-dependent functions in apicomplexan parasites,” ACS Chem Biol., Apr. 17, 2015, 10(4):1145-1154. [cited by applicant]

Howington et al., “Treatment of Stage I and II Non-small Cell Lung Cancer Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines,” Chest, May 20… [cited by applicant]

Hu et al., “Discovery of 3,5-substituted 6-azaindazoles as potent pan-Pim inhibitors,” Bioorg Med Chem Lett., 2015, 25(22):5258-5264. [cited by applicant]

Hu et al., “Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade,” Genes Dev, 1996, 10(18): p. 2251-2264. [cited by applicant]

Hudis et al., “Triple-Negative Breast Cancer: An Unmet Medical Need,” The Oncologist, 2011, 16(suppl 1):1-11. [cited by applicant]

Ikegami et al., “The expression of prostaglandin E receptors EP2 and EP4 and their different regulation by lipopolysaccharide in C3H/HeN peritoneal macrophages,” J. Immunol., Apr. 2001, 166(7): 4689-4696. [cited by applicant]

Indian Office Action in Indian Application No. 201917010977, dated Nov. 27, 2020, 5 pages. [cited by applicant]

Indian Office Action in Indian Application No. 202017040632, dated Mar. 7, 2022, 7 pages. [cited by applicant]

Indian Oral Hearing in Indian Application No. 201917010977, dated Aug. 13, 2021, 2 pages. [cited by applicant]

Indian Oral Hearing in Indian Application No. 201917010977, dated Sep. 16, 2021, 2 pages. [cited by applicant]

International Preliminary Report on Patentability in International Application No. PCT/US2017/050669, dated Mar. 12, 2019, 8 pages. [cited by applicant]

International Preliminary Report on Patentability in International Application No. PCT/US2017/050727, dated Mar. 12, 2019, 8 pages. [cited by applicant]

International Preliminary Report on Patentability in International Application No. PCT/US2017/050737, dated Mar. 12, 2019, 8 pages. [cited by applicant]

International Preliminary Report on Patentability in International Application No. PCT/US2017/050757, dated Mar. 12, 2019, 10 pages. [cited by applicant]

International Preliminary Report on Patentability in International Application No. PCT/US2018/018205, dated Aug. 20, 2019, 10 pages. [cited by applicant]

International Preliminary Report on Patentability in International Application No. PCT/US2018/049908, dated Mar. 10, 2020, 8 pages. [cited by applicant]

International Preliminary Report on Patentability in International Application No. PCT/US2019/018608, dated Aug. 27, 2020, 8 pages. [cited by applicant]

International Preliminary Report on Patentability in International Application No. PCT/US2019/018609, dated Aug. 27, 2020, 7 pages. [cited by applicant]

International Preliminary Report on Patentability in International Application No. PCT/US2020/044919, dated Feb. 8, 2022, 9 pages. [cited by applicant]

International Search Report and Written Opinion in International Application No. PCT/US2017/048880, dated Nov. 2, 2017, 15 pages. [cited by applicant]

International Search Report and Written Opinion in International Application No. PCT/US2017/050669, dated Nov. 6, 2017, 16 pages. [cited by applicant]

International Search Report and Written Opinion in International Application No. PCT/US2017/050727, dated Nov. 2, 2017, 16 pages. [cited by applicant]

International Search Report and Written Opinion in International Application No. PCT/US2017/050737, dated Nov. 2, 2017, 16 pages. [cited by applicant]

International Search Report and Written Opinion in International Application No. PCT/US2017/050757, dated Nov. 10, 2017, 20 pages. [cited by applicant]

International Search Report and Written Opinion in International Application No. PCT/US2018/018205, dated Apr. 30, 2018, 16 pages. [cited by applicant]

International Search Report and Written Opinion in International Application No. PCT/US2018/049908, dated Nov. 7, 2018, 15 pages. [cited by applicant]

International Search Report and Written Opinion in International Application No. PCT/US2019/018608, dated Apr. 16, 2019, 14 pages. [cited by applicant]

International Search Report and Written Opinion in International Application No. PCT/US2019/018609, dated May 13, 2019, 12 pages. [cited by applicant]

Cited By (1)

US 12,516,059