Granted Patent B2

US 12,552,804 · App. 18/545,487 · Granted Feb 17, 2026

Inventors: Matthew S. McCammant (Newark, DE); Evan Styduhar (Media, PA); Oleg Vechorkin (Wilmington, DE); Robert Swyka (Wilmington, DE); Wenqing Yao (Chadds Ford, PA)

Assignee: Incyte Corporation

C07D487/14A61P35/00C07D471/14

Abstract

Claims (120)

1 . A compound having Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

X is NR 5 ;

Y is C;

represents a single bond or a double bond;

Z is N;

Cy 1 is 5-10 membered heteroaryl; wherein each 5-10 membered heteroaryl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the 5-10 membered heteroaryl is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R10;

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

R 1 , R 2 , and R 3 are each independently selected from H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, halo, CN, OR a9 , and NR c9 R d9 ;

R 5 is selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, and C 6-10 aryl; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, and C 6-10 aryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 50 ;

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, D, 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 , 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 e1 R d1 , NR e1 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 e1 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 ;

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, D, 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 C(O)NR c3 R d3 , 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, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, 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 C(O)NR c5 R d5 , 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, 5-6 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 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, D, 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 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, D, 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 C(O)NR c4 R d4 , 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 ;

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, D, 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 C(O)NR c6 R d6 , NR c6 S(O)R b6 , NR c6 S(O) 2 R b6 , NR c6 S(O) 2 NR c6 OR 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 50 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a11 and NR c11 R d11 ;

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 c1 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl) carbamyl, 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 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, 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 c2 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 e5 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 ;

or any R c5 and R d5 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 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 a9 , R e9 , and R d9 is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl;

each R a11 , R c11 and R d11 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 ; and

each R g is independently selected from D, 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 alkoxycarbonylamino, C 1-6 alkylcarbonyloxy, aminocarbonyloxy, C 1-6 alkylaminocarbonyloxy, di(C 1-6 alkyl)aminocarbonyloxy, 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.

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

ring A is aromatic.

3 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is pyrazolyl or pyridinyl, each optionally substituted with 1 or 2 substituents independently selected from R 10 .

4 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is selected from 1-methyl-1H-pyrazol-4-yl, 1,3-dimethyl-1H-pyrazol-4-yl, 1-(1-acetylpyrrolidin-3-yl)-1H-pyrazol-4-yl, 1-(4-carboxycyclohexyl)-1H-pyrazol-4-yl, 1-(4-acetamidocyclohexyl)-1H-pyrazol-4-yl, 1-(3-hydroxycyclobutyl)-1H-pyrazol-4-yl, and 6-(4-acetylpiperazin-1-yl)pyridin-3-yl.

5 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is selected from 1-methyl-1H-pyrazol-4-yl, 1,3-dimethyl-1H-pyrazol-4-yl, 1-(1-acetylpyrrolidin-3-yl)-1H-pyrazol-4-yl, 1-(4-carboxycyclohexyl)-1H-pyrazol-4-yl, 1-(4-acetamidocyclohexyl)-1H-pyrazol-4-yl, 1-(3-hydroxycyclobutyl)-1H-pyrazol-4-yl, 6-(4-acetylpiperazin-1-yl)pyridin-3-yl, 1-(1-(2-hydroxyacetyl)pyrrolidin-3-yl)-1H-pyrazol-4-yl, 1-(1-(1-aminocyclopropane-1-carbonyl)azetidin-3-yl)-1H-pyrazol-4-yl, 1-(1-(2-(1H-imidazol-1-yl)acetyl)azetidin-3-yl)-1H-pyrazol-4-yl, 1-(1-(oxazole-4-carbonyl)azetidin-3-yl)-1H-pyrazol-4-yl, 1-(1-(4-aminotetrahydro-2H-pyran-4-carbonyl)azetidin-3-yl)-1H-pyrazol-4-yl, 1-(1-(2-cyanoacetyl)azetidin-3-yl)-1H-pyrazol-4-yl, 1-(4-carboxy-3-fluorobenzyl)-1H-pyrazol-4-yl, 1-(4-(dimethylcarbamoyl)phenyl)-1H-pyrazol-4-yl, 1-((1r,4r)-4-(2-methoxyacetamido)cyclohexyl)-1H-pyrazol-4-yl, 1-((1r,4r)-4-(3,3-dimethylureido)cyclohexyl)-1H-pyrazol-4-yl, 1-(2-acetyl-2-azaspiro[3.5]nonan-7-yl)-1H-pyrazol-4-yl, 1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl, 1-((1r,4r)-4-hydroxycyclohexyl)-1H-pyrazol-4-yl, 1-(4-carboxy-4-methylcyclohexyl)-1H-pyrazol-4-yl, 1-(1-(dimethylcarbamoyl)pyrrolidin-3-yl)-1H-pyrazol-4-yl, 1-(1-(N,N-dimethylsulfamoyl)pyrrolidin-3-yl)-1H-pyrazol-4-yl, 1-(3-(2-hydroxyacetyl)-3-azabicyclo[3.1.0]hexan-1-yl)-1H-pyrazol-4-yl, 1-(1-(morpholine-4-carbonyl)pyrrolidin-3-yl)-1H-pyrazol-4-yl, 1-(3-(2-hydroxyacetyl)-3-azabicyclo[4.1.0]heptan-6-yl)-1H-pyrazol-4-yl, 1-(3-acetyl-3-azabicyclo[4.1.0]heptan-1-yl)-1H-pyrazol-4-yl, 6-(1-(2-hydroxyacetyl)azetidin-3-yl)pyridin-3-yl, 5-(1-acetylazetidin-3-yl)pyridin-3-yl, 1-cyclopropyl-1H-pyrazol-4-yl, 1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl, 1-(oxetan-3-yl)-1H-pyrazol-4-yl, 1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl, 1-isopropyl-1H-pyrazol-4-yl, 1-(difluoromethyl)-1H-pyrazol-4-yl, 1-(2-cyanoethyl)-1H-pyrazol-4-yl, 1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl, 1-(cyanomethyl)-1H-pyrazol-4-yl, 1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl, 1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl, 1-(2-(methylsulfonyl)ethyl)-1H-pyrazol-4-yl, 1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl, 1-(2-morpholinoethyl)-1H-pyrazol-4-yl, and 1-(2-hydroxyethyl)-1H-pyrazol-4-yl.

6 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from C 1-6 alkyl, 4-10 membered heterocycloalkyl, and C 3-10 cycloalkyl, each of which is optionally substituted with 1 or 2 substituents independently selected from R 11 .

7 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, phenyl, 4-10 membered heterocycloalkyl, and C 3-10 cycloalkyl, each of which is optionally substituted with 1 or 2 substituents independently selected from R 11 .

8 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from methyl, ethyl, isopropyl, 2-methylpropyl, difluoromethyl, cyclopropyl, cyclobutyl, cyclohexyl, phenyl, piperzinyl, azetidinyl, pyrrolidinyl, azaspiro[3.5]nonanyl, tetrahydro-2H-pyranyl, azabicyclo[3.1.0]hexanyl, azabicyclo[4.1.0]heptanyl, tetrahydrofuranyl, oxetanyl, and piperidinyl, each of which is optionally substituted with 1 or 2 substituents independently selected from R 11 .

9 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently selected from C(O)R b3 , C(O)OR a3 , NR 3 C(O)R b3 , and OR a3 .

10 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently selected from C 1-6 alkyl, CN, C(O)R b3 , C(O)OR a3 , NR c3 C(O)R b3 , OR a3 , C(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)NR c3 R d3 , S(O) 2 NR c3 R d3 , S(O) 2 R b3 , phenyl, and 4-6 membered heterocycloalkyl, wherein said C 1-6 alkyl, phenyl, and 4-6 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R 12 .

11 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently selected from C(O)CH 3 , C(O)OH, NHC(O)CH 3 , and OH.

12 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently selected from methyl, CN, OH, C(O)CH 3 , C(O)OH, NHC(O)CH 3 , C(O)CH 2 OH, C(O)N(CH 3 ) 2 , NHC(O)CH 2 OCH 3 , NHC(O)N(CH 3 ) 2 , S(O) 2 N(CH 3 ) 2 , N(CH 3 ) 2 , S(O) 2 CH 3 , 2-cyanoacetyl, morpholine-4-carbonyl, morpholinyl, 1-aminocyclopropane-1-carbonyl, (1H-imidazol-1-yl)acetyl, oxazole-4-carbonyl, 4-aminotetrahydro-2H-pyran-4-carbonyl, and 4-carboxy-3-fluorophenyl.

13 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy A is selected from phenyl and 5-6 membered heteroaryl, wherein the phenyl and 5-6 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 20 .

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

15 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy A is selected from 2-chlorophenyl, 2,6-difluorophenyl, 2-chloro-6-fluorophenyl, 2,6-dichlorophenyl, 2-fluoro-6-methylphenyl, 2-chloro-4-methoxyphenyl, and 3-methylfuran-2-yl.

16 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy A is selected from 2-chlorophenyl, 2,6-difluorophenyl, 2-chloro-6-fluorophenyl, 2,6-dichlorophenyl, 2-fluoro-6-methylphenyl, 2-chloro-4-methoxyphenyl, 3-methylfuran-2-yl, 1-methylpiperidin-4-yl, (1S,5R)-2-oxo-3,8-diazabicyclo[3.2.1]octan-8-yl, 2-chloro-6-(trifluoromethyl)phenyl, 2,6-dimethylphenyl, 2-cyano-6-fluorophenyl, 2-fluoro-6-methoxyphenyl, 2,3-dimethylphenyl, 4-(hydroxymethyl)-2-methylphenyl, 3-acrylamido-2,6-dichlorophenyl, 3-acrylamidophenyl, 2-acrylamidophenyl, and cyclopropyl.

17 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from halo, C 1-6 alkyl, and OR a2 .

18 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from halo, CN, C 1-6 alkyl, C 1-6 haloalkyl, and NR c2 C(O)R b2 , wherein the C 1-6 alkyl is optionally substituted with OR a4 .

19 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from chloro, fluoro, methyl, and methoxy.

20 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from CN, chloro, fluoro, methyl, methoxy, trifluoromethyl, hydroxymethyl, and acrylamido.

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

22 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is H, OR a9 , or NR c9 R d9 .

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

24 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is H.

25 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is C 1-6 alkyl.

26 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is methyl.

27 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound has Formula IIIa:

28 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound has Formula IIIb:

wherein n is 0, 1, 2, or 3.

29 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound has Formula IIIc:

wherein n is 0, 1, 2, or 3.

30 . The compound of claim 1 , having Formula (IA):

or a pharmaceutically acceptable salt thereof, wherein:

Z is N;

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

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

R 1 , R 2 , and R 3 are each independently selected from H, D, C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a9 , and NR c9 R d9 ;

R 5 is selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, and C 6-10 aryl; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, and C 6-10 aryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 50 ;

each R 10 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a1 , and NR c1 R d1 , wherein said C 1-6 alkyl, C 3-10 cycloalkyl, and 4-10 membered heterocycloalkyl 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 1-6 haloalkyl, C 3-10 cycloalkyl, halo, D, CN, OR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , and S(O) 2 R b3 ; wherein said C 1-6 alkyl, and C 3-10 cycloalkyl 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, halo, D, CN, OR a5 and NR c5 R d5 ;

each R 20 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, halo, D, CN, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , S(O)NR c2 R d2 , and S(O) 2 R b2 ; wherein said C 1-6 alkyl, and C 3-10 cycloalkyl 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 1-6 haloalkyl, halo, D, CN, OR a4 , and NR c4 R a4 ;

each R 50 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a11 , and NR c11 R d11 ;

each R a1 , R c1 and R d1 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, and 4-10 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, and 4-10 membered heterocycloalkyl 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-, or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 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 C 3-10 cycloalkyl; wherein said C 1-6 alkyl and C 3-10 cycloalkyl are each 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 1-6 haloalkyl, and C 3-10 cycloalkyl; wherein said C 1-6 alkyl and C 3-10 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ;

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

each R b3 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, and C 3-6 cycloalkyl; wherein said C 1-6 alkyl and C 3-6 cycloalkyl 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, and C 1-6 haloalkyl;

each R a5 , R c5 and R d5 is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl;

each R a9 , R c9 , and R d9 is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl; and

each R a11 , R c11 and R d11 is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl.

31 . The compound of claim 1 , having Formula (IA):

or a pharmaceutically acceptable salt thereof, wherein:

Z is N;

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

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

R 1 , R 2 , and R 3 are each independently selected from H, D, C 1-6 alkyl, C 1-6 haloalkyl, halo, and CN;

R 5 is selected from C 1-6 alkyl and C 1-6 haloalkyl;

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

each R 11 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a3 , C(O)R b3 , C(O)NR c3 R d3 , and NR c3 R d3 ,

each R 20 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a2 , and NR c2 R d2 ;

each R a1 , R c1 and R d1 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, and 4-10 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1 or 2 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-, or 6-membered heterocycloalkyl group 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, and C 1-6 haloalkyl;

each R a3 , R c3 and R d3 , is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl; and

each R b3 is independently selected from C 1-6 alkyl and C 1-6 haloalkyl.

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

2-(2-Fluoro-6-methylphenyl)-3-methyl-8-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-f]quinoxaline;

2-(2-Chloro-4-methoxyphenyl)-3-methyl-8-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-f]quinoxaline;

3-Methyl-8-(1-methyl-1H-pyrazol-4-yl)-2-(3-methylfuran-2-yl)-3H-imidazo[4,5-f]quinoxaline;

3-(4-(2-(2-Chloro-6-fluorophenyl)-3-methyl-3H-imidazo[4,5-f]quinoxalin-8-yl)-1H-pyrazol-1-yl)cyclobutan-1-ol; and

1-(4-(5-(2-(2-Chloro-6-fluorophenyl)-3-methyl-3H-imidazo[4,5-f]quinoxalin-8-yl)pyridin-2-yl)piperazin-1-yl)ethan-1-one,

or a pharmaceutically acceptable of any of the aforementioned.

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

3-Methyl-8-(1-methyl-1H-pyrazol-4-yl)-2-(1-methylpiperidin-4-yl)-3H-imidazo[4,5-f]quinoxaline; and

(1S,5R)-8-(3-Methyl-8-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-f]quinoxalin-2-yl)-3,8-diazabicyclo[3.2.1]octan-2-one;

or a pharmaceutically acceptable salt of any of the aforementioned.

34 . A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

Assignments (1)

Continuity (3)

References Cited (400)