US2023192696A1PendingUtilityA1
Spiro compounds as inhibitors of kras
Est. expiryJan 20, 2040(~13.5 yrs left)· nominal 20-yr term from priority
C07D 498/20C07D 471/20C07D 471/22C07D 491/20C07D 471/10A61P 35/00A61P 29/00A61P 37/00
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Claims
Abstract
Disclosed are compounds of Formula I, methods of using the compounds for inhibiting KRAS activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with KRAS activity such as cancer.
Claims
exact text as granted — not AI-modified1 . A method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of compound having Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
represents a single bond or a double bond;
X is N or CR 7 ;
Y is O, NR 5N , C═O, or C(R 5 ) 2 ;
W is C═O, or C(R 8 ) 2 ;
Z is O, NR 9N , O(R 9 ) 2 , or a bond;
R 1 is selected from H, D, 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 a1 , SR a1 , C(O)R1 b , 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 , 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 , S(O) 2 NR c1 R d1 , and BR h1 R i1 ; 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 ;
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, 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 C(═NR e2 )R b2 , 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 S(O) 2 NR c2 R d2 , and BR h2 R i2 ; 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 20 ;
Cy 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 10 ;
when of R 3 N R 4 is a single bond, then R 4 is selected from ═O and ═S; and
R 3 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, and 5-10 membered heteroaryl-C 1-3 alkylene; 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 ; or
when of R 3 N R 4 is a double bond, then R 3 is absent; and
R 4 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, D, CN, NO 2 , OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , NR c3 C(O)NR c3 R d3 , C(═NR e3 )R b3 , C(═NOR a3 )R b3 , C(═NR e3 )NR c3 R d3 , NR c5 C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )R b3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , S(O) 2 NR c3 R d3 , and BR h3 R i3 ; 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 ;
R 5N 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, and 5-10 membered heteroaryl-C 1-3 alkylene; 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 50 ;
each R 5 and R 8 are 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, 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 a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)OR a5 , NR c5 C(O)NR c5 R d5 , C(═NR e5 )R b5 , C(═NOR a5 )R b5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )R b5 , 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 , S(O) 2 NR c5 R d5 , and BR h5 R i5 ; 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 50 ;
ring A is selected from C 3-10 cycloalkyl and 4-14 membered heterocycloalkyl; wherein the 4-14 membered heterocycloalkyl 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 4-14 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group;
n is 0, 1, 2, 3, or 4;
each R 6 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 a6 , SR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , OC(O)R b6 , OC(O)NR c6 R d6 , NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)OR a6 , NR c6 C(O)NR c6 R d6 , C(═NR e6 )R b6 , C(═NOR a6 )R b6 , C(═NR e6 )NR c6 R d6 , NR c6 C(═NR e6 )NR c6 R d6 , NR c6 C(═NR e6 )R b6 , 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 S(O) 2 NR c6 R d6 , and BR h6 R i6 ; 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 60 ;
R 7 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, D, CN, NO 2 , OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)OR a7 , NR c7 C(O)NR c7 R d7 , C(═NR e7 )R b7 , C(═NOR a7 )R b7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )R b7 , 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 , S(O) 2 NR c7 R d7 , and BR h7 R i7 ; 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 70 ;
R 9N is 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 ;
each R 9 is independently selected from selected from H, D, 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 a9 , SR a9 , C(O)R b9 , C(O)NR c9 R d9 , C(O)OR a9 , OC(O)R b9 , OC(O)NR c9 R d9 , NR c9 R d9 , NR c9 C(O)R b9 , NR c9 C(O)OR a9 , NR c9 C(O)NR c9 R d9 , NR c9 S(O)R b9 , NR c9 S(O) 2 R b9 , NR c9 S(O) 2 NR c9 R d9 , S(O)R b9 , S(O)NR c9 R d9 , S(O) 2 R b9 , S(O) 2 NR c9 R d9 , and BR h9 R i9 ; 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 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 a10 , SR a10 , C(O)R b10 , C(O)NR c10 R d10 , C(O)OR a1 °, OC(O)R b10 , OC(O)NR c10 R d10 , NR c10 R d10 , NR c10 C(O)R b10 , NR c10 C(O)OR a10 , NR c10 C(O)NR c10 R d10 , C(═NR e10 )R b10 , C(═NOR a10 )R b10 , C(═NR e10 )NR c10 R d10 , NR c10 C(═NR e10 )NR c10 R d10 , NR c10 C(═NR e10 )R b10 , NR c10 S(O)R b10 , NR c10 S(O) 2 R b10 , NR c10 S(O) 2 NR c10 R d10 , S(O)R b10 , S(O)NR c10 R d10 , S(O) 2 R b10 , S(O) 2 NR c10 R d10 , and BR h10 R i10 ; 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 a11 , SR a11 , C(O)R b11 , C(O)NR c11 R d11 , C(O)OR a11 , OC(O)R b11 , OC(O)NR c11 R d11 , NR c11 R d11 , NR c11 C(O)R b11 , NR c11 C(O)OR a11 , NR c11 C(O)NR c11 R d11 , NR c11 S(O)R b11 , NR c11 S(O) 2 R b11 , NR c11 S(O) 2 NR c11 R d11 , S(O)R b11 , S(O)NR c11 R d11 , S(O) 2 R b11 S(O) 2 NR c11 R d11 , and BR h11 R i11 ; 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, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a12 , SR a12 , C(O)R b12 , C(O)NR c12 R d12 , C(O)OR a12 , OC(O)R b12 , OC(O)NR c12 R d12 , NR c12 R d12 , NR c12 C(O)R b12 , NR c12 C(O)OR a12 , NR c12 C(O)NR c12 R d12 , NR c12 S(O)R b12 , NR c12 S(O) 2 R b12 , NR c12 S(O) 2 NR c12 R d12 S(O)R b12 , S(O)NR c12 R d12 S(O) 2 R b12 S(O) 2 NR c12 R d12 , and BR h12 R i12 ; 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 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 a20 , SR a20 , C(O)R b20 , C(O)NR c20 R d20 , C(O)OR a20 , OC(O)R b20 , OC(O)NR c20 R d20 , NR c20 R d20 , NR c20 C(O)R b20 , NR c20 C(O)OR a20 , NR c20 C(O)NR c20 R d20 , NR c20 S(O)R b20 , NR c20 S(O) 2 R b20 , NR c20 S(O) 2 NR c20 R d20 S(O)R b20 ; S(O)NR c20 R d20 , S(O) 2 R b20 , S(O) 2 NR c20 R d20 , and BR h20 R i20 ; 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 a21 , SR a21 , C(O)R b21 , C(O)NR c21 R d21 , C(O)OR a21 , OC(O)R b21 , OC(O)NR c21 R d21 , NR c21 R d21 , NR c21 C(O)R b21 , NR c21 C(O)OR a21 , NR c21 C(O)NR c21 R d21 , NR c21 S(O)R b21 , NR c21 S(O) 2 R b21 , NR c21 S(O) 2 NR c21 R d21 , S(O)R b21 , S(O)NR c21 R d21 , S(O) 2 R b21 , S(O) 2 NR c21 R d21 , and BR h21 R i21 ; 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 a22 , SR a22 , C(O)R b22 , C(O)NR c22 R d22 , C(O)OR a22 , OC(O)R b22 , OC(O)NR c22 R d22 , NR c22 R d22 , NR c22 C(O)R b22 , NR c22 C(O)OR a22 , NR c22 C(O)NR c22 R d22 , NR c22 S(O)R b22 , NR c22 S(O) 2 R b22 , NR c22 S(O) 2 NR c22 R d22 S(O)R b22 , S(O)NR c22 R d22 , S(O) 2 R b22 , S(O) 2 NR c22 R d22 , and BR h22 R i22 ; 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 3-10 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 a30 , SR a30 , C(O)R b30 , C(O)NR c30 R d30 , C(O)OR a30 , OC(O)R b30 , OC(O)NR c30 R d30 , NR c30 R d30 , NR c30 C(O)R b30 , NR c30 C(O)OR a30 , NR c30 C(O)NR c30 R d30 , C(═NR e30 )R b30 , C(═NOR a30 )R b30 , C(═NR e30 )NR c30 R d30 , NR c30 C(═NR e30 )NR c30 R d30 , NR c30 C(═NR e30 )R b30 , NR c3 S(O)R b30 , NR c30 S(O) 2 R b30 , NR c30 S(O) 2 NR c30 R d30 , S(O)R b30 , S(O)NR c30 R d30 , S(O) 2 R b30 , S(O) 2 NR c30 R d30 , and BR h30 R i30 ; 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 31 ;
each R 31 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 a31 , SR a31 , C(O)R b31 , C(O)NR c1 R d31 , C(O)OR a31 , OC(O)R b31 , OC(O)NR c31 R d31 , NR c31 R d31 , NR c31 C(O)R b31 , NR c31 C(O)OR a31 , NR c31 C(O)NR c31 R d31 , NR c31 S(O)R b31 , NR c31 S(O) 2 R b31 , NR c31 S(O) 2 NR c31 R d31 , S(O)R b31 , S(O)NR c31 R d31 , S(O) 2 R b31 , S(O) 2 NR c31 R d31 , and BR h31 R i31 ; 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 32 ;
each R 32 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 a32 , SR a32 , C(O)R b32 , C(O)NR c32 R d32 , C(O)OR a32 , C(O)R b32 , OC(O)NR c32 R d32 , NR c32 R d32 , NR c32 C(O)R b32 , NR 32 C(O)OR a32 , NR c32 C(O)NR c32 R d32 , NR c32 S(O)R b32 , NR c32 S(O) 2 R b32 , NR c32 S(O) 2 NR c32 R d32 S(O)R b32 , S(O)NR c32 R d32 , S(O) 2 R b32 , S(O) 2 NR c32 R d32 , and BR h32 R i32 ; 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 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 a50 , SR a50 , C(O)R b50 , C(O)NR c50 R d50 , C(O)OR a50 , OC(O)R b50 , OC(O)NR c5 R d50 , NR c50 R d50 , NR c50 C(O)R b50 , NR c50 C(O)OR d50 , NR c50 C(O)NR c50 R d50 , NR c50 S(O)R b50 , NR c50 S(O) 2 R b50 , NR c50 S(O) 2 NR c50 R d50 , S(O)R b50 , S(O)NR c50 R d50 , S(O) 2 R b50 , S(O) 2 NR c50 R d50 , and BR h50 R i50 ; 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 51 ;
each R 51 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 a51 , SR a51 , C(O)R b51 , C(O)NR c51 R d51 , C(O)OR a51 , OC(O)R b51 , OC(O)NR c51 R d51 , NR c51 R d51 , NR c51 C(O)R b51 , NR c51 C(O)OR a51 , NR c51 C(O)NR c51 R d51 , NR c51 S(O)R b51 , NR c51 S(O) 2 R b51 , NR c51 S(O) 2 NR c51 R d51 , S(O)R b51 , S(O)NR c51 R d51 , S(O) 2 R b51 S(O) 2 NR c51 R d51 , and BR h51 R i51 ; 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 52 ;
each R 52 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 a52 , SR a52 , C(O)R b52 , C(O)NR c52 R d52 , C(O)OR a5 2 OC(O)R b52 , OC(O)NR c52 R d52 , NR c52 R d52 , NR c52 C(O)R b52 , NR c52 C(O)OR d52 , NR c52 C(O)NR c52 R d52 , NR c52 S(O)R b52 , NR c52 S(O) 2 R b52 , NR c52 S(O) 2 NR c52 R d52 , S(O)R b52 , S(O)NR c52 R d52 , S(O) 2 R b52 , S(O) 2 NR c52 R d52 , and BR h52 R i52 ; 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 60 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 a60 , SR a60 , C(O)R b60 , C(O)NR c60 R d60 , C(O)OR a60 , OC(O)R b60 , OC(O)NR c60 R d60 , NR c60 R d60 , NR c60 C(O)R b60 , NR c60 C(O)OR a60 , NR c60 C(O)NR c60 R d60 , NR c60 S(O)R d60 , NR c60 S(O) 2 R b60 , NR c60 S(O) 2 NR c60 R d60 S(O)R b60 , S(O)NR c60 R d60 , S(O) 2 R b60 , S(O) 2 NR c60 R d60 , and BR b60 R c60 ; 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 g ;
each R 70 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 a70 , SR a70 , C(O)R b70 , C(O)NR c70 R d70 , C(O)OR a70 , OC(O)R b70 , OC(O)NR c70 R d70 , NR c70 R d70 , NR c70 C(O)R b70 , NR c70 C(O)OR a70 , NR c70 C(O)NR c70 R d70 , NR c70 S(O)R b70 , NR c70 S(O) 2 R b70 , NR c70 S(O) 2 NR c70 R d70 S(O)R b70 , S(O)NR c70 R d70 , S(O) 2 R b70 , S(O) 2 NR c7 R d70 , and BR h70 R i70 ; 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 71 ;
each R 71 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 a71 , SR a71 , C(O)R b71 , C(O)NR c71 R d71 , C(O)OR a71 , OC(O)R b71 , OC(O)NR c71 R d71 , NR c71 R d71 , NR c71 C(O)R b71 , NR c71 C(O)OR a71 , NR c71 C(O)NR c71 R d71 , NR c71 S(O)R b71 , NR c71 S(O) 2 R b71 , NR c71 S(O) 2 NR c71 R d71 S(O)R b71 , S(O)NR c71 R d71 , S(O) 2 R b71 , S(O) 2 NR c71 R d71 , and BR b71 R i71 ; 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 72 ;
each R 72 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 a72 , SR a72 , C(O)R b72 , C(O)NR c72 R d72 , C(O)OR a72 , OC(O)R b72 , OC(O)NR c72 R d72 , NR c72 R d72 , NR c72 C(O)R b72 , NR c72 C(O)OR a72 , NR c72 C(O)NR c72 R d72 , NR c72 S(O)R b72 , NR c72 S(O) 2 R b72 , NR c72 S(O) 2 NR c72 R d72 S(O)R b72 , S(O)NR c72 R d72 S(O) 2 R b72 S(O) 2 NR c72 R d72 , and BR h72 R i72 ; 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 a1 , R b1 , 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 3-6 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 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 or 3 substituents independently selected from R g ;
each R h1 and R i1 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h1 and R i1 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a2 , R b2 , 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 20 ;
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 20 ;
each R e2 is independently selected from H, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 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 h2 and R i2 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h2 and R i2 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a3 , R b3 , 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 3-10 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; 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 ;
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, 3, or 4 substituents independently selected from R 30 ;
each R e3 is independently selected from H, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 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 h3 and R i3 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h3 and R i3 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a5 , R b5 , R c5 and R d5 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 50 ;
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 50 ;
each R e5 is independently selected from H, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 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 h5 and R i5 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h5 and R i5 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a6 , R b6 , R c6 and R d6 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 60 ;
or any R c6 and R d6 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 60 ;
each R e6 is independently selected from H, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 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 h6 and R i6 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h6 and R i6 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a7 , R b7 , 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 70 ;
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, 3, or 4 substituents independently selected from R 70 ;
each R e7 is independently selected from H, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 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 h7 and R i7 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h7 and R i7 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a9 , R b9 , R c9 , and R d9 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 c9 and R d9 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 h9 and R i9 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h9 and R i9 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a10 , R b10 , R c10 and R d10 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 c10 and R d10 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 e10 is independently selected from H, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 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 h10 and R i10 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h10 and R i10 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a11 , R b11 , R c11 and R d11 , 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 c11 and R d11 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 h11 and R i11 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h11 and R i11 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a12 , R b12 , R c12 and R d12 , 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 h12 and R i12 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h12 and R i12 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a20 , R b20 , R c20 and R d20 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 c20 and R d20 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 h20 and R i20 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h20 and R i20 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a21 , R b21 , R c21 and R d21 , 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 c21 and R d2 1 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 h21 and R i21 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h21 and R i21 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a22 , R b22 , R c22 and R d22 , 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 h22 and R i22 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h22 and R i22 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a30 , R b30 , R c30 and R d30 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 31 ;
or any R c30 and R d30 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 31 ;
each R e30 is independently selected from H, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 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 h30 and R i30 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h30 and R i30 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a31 , R b31 , R c31 and R d31 , 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 32 ;
or any R c31 and R d31 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 32 ;
each R h31 and R i31 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h31 and R i31 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a32 , R b32 , R c32 and R d32 , 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 h32 and R i32 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h32 and R i32 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a50 , R b50 , R c50 and R d50 , 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 1-6 haloalkyl, 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 51 ;
or any R c50 and R d50 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 51 ;
each R h50 and R i50 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h50 and R i50 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a51 , R b51 , R c51 and R d51 , 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 52 ;
or any R c51 and R d51 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 52 ;
each R h51 and R i51 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h51 and R i51 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a52 , R b52 , R c52 and R d52 , 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 h52 and R i52 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h52 and R i32 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a60 , R b60 , R c60 and R d60 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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 1-6 haloalkyl, 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 g ;
or any R c60 and R d60 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 h60 and R i60 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h60 and R i60 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a70 , R b70 , R c70 and R d70 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 71 ;
or any R c70 and R d70 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 71 ;
each R h70 and R i70 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h70 and R i70 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a71 , R b71 , R c71 and R d71 , 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 72 ;
or any R c71 and R d71 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 72 ;
each R h71 and R i71 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h71 and R i71 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl;
each R a72 , R b72 , R c72 and R d72 , 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 h72 and R i72 is independently selected from OH, C 1-6 alkoxy, and C 1-6 haloalkoxy; or any R h72 and R i72 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl; 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 method of claim 1 , wherein
represents a single bond or a double bond; X is N or CR 7 ; Y is O, NR 5N , C═O, or O(R 5 ) 2 ; W is C═O, or C(R 8 ) 2 ; Z is O, NR 9N , O(R 9 ) 2 , or a bond; R 1 is selected from H, D, 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 a1 , SR a1 , C(O)R1 b , 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 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 , 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, D, CN, OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 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 20 ; Cy 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 10 ; when of R 3 N CR 4 is a single bond, then R 4 is selected from ═O and ═S; and R 3 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, and 5-10 membered heteroaryl-C 1-3 alkylene; 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 ; or when of R 3 N OR 4 is a double bond, then R 3 is absent; and R 4 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, D, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , NR c3 C(O)NR c3 R d3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 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 30 ; R 5N 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, and 5-10 membered heteroaryl-C 1-3 alkylene; 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 50 ; each R 5 and R 8 are 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, 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 a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)OR a5 , NR c5 C(O)NR c5 R d5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ; ring A is selected from C 3-10 cycloalkyl and 4-14 membered heterocycloalkyl; wherein the 4-14 membered heterocycloalkyl 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 4-14 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; n is 0, 1, or 2; each R 6 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 a6 , SR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , OC(O)R b6 , OC(O)NR c6 R d6 , NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)OR a6 , NR c6 C(O)NR c6 R d6 , NR c6 S(O) 2 R b6 , NR c6 S(O) 2 NR c6 R d6 , S(O) 2 R b6 , and S(O) 2 NR c6 R d6 ; R 7 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, D, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)OR a7 , NR c7 C(O)NR c7 R d7 NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , S(O) 2 R b7 , and S(O) 2 NR c7 R d7 ; R 9N is 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; each R 9 is independently selected from selected from H, D, 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 a9 , SR a9 , C(O)R b9 , C(O)NR c9 R d9 , C(O)OR a9 , OC(O)R b9 , OC(O)NR c9 R d9 , NR c9 R d9 , NR c9 C(O)R b9 , NR c9 C(O)OR a9 , NR c9 C(O)NR c9 R d9 , NR c9 S(O) 2 R b9 , NR c9 S(O) 2 NR c9 R d9 , S(O) 2 R b9 , and S(O) 2 NR c9 R d9 ; 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, OR a10 , SR a10 , C(O)R b10 , C(O)NR c10 R d10 , C(O)OR a10 , OC(O)R b10 , OC(O)NR c10 R d10 , NR c10 R d10 , NR c10 C(O)R b10 , NR c10 C(O)OR a10 , NR c10 C(O)NR c10 R d10 , NR c10 S(O) 2 R b10 , NR c10 S(O) 2 NR c10 R d10 , S(O)R b10 , and S(O) 2 NR c10 R d10 ; 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, OR a20 , SR a20 , C(O)R b20 , C(O)NR c20 R d20 , C(O)OR a20 , OC(O)R b20 , OC(O)NR c20 R d20 , NR c20 R d20 , NR c20 C(O)R b20 , NR c20 C(O)OR a20 , NR c20 C(O)NR c20 R d20 , NR c20 S(O) 2 R b20 , NR c20 S(O) 2 NR c20 R d20 S(O) 2 R b20 and S(O) 2 NR c20 R d20 ; 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 a21 , SR a21 , C(O)R b21 , C(O)NR c21 R d21 , C(O)OR a21 , OC(O)R b21 , OC(O)NR c21 R d21 , NR c21 R d21 , NR c21 C(O)R b21 , NR c21 C(O)OR a21 , NR c21 C(O)NR c21 R d21 , NR c21 S(O) 2 R b21 , NR c21 S(O) 2 NR c21 R d21 , S(O) 2 R b21 , and S(O) 2 NR c21 R d21 ; each R 30 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 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 a30 , SR a30 , C(O)R b30 , C(O)NR c30 R d30 , C(O)OR a30 , OC(O)R b30 , OC(O)NR c30 R d30 , NR c30 R d30 , NR c30 C(O)R b30 , NR c30 C(O)OR a30 , NR c30 C(O)NR c30 R d30 , NR c30 S(O) 2 R b30 , NR c30 S(O) 2 NR c30 R d30 , S(O) 2 R b30 , and S(O) 2 NR c30 R d30 ; 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 31 ; each R 31 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 a31 , SR a31 , C(O)R b31 , C(O)NR c1 R d31 , C(O)OR a31 , OC(O)R b31 , OC(O)NR c31 R d31 , NR c31 R d31 , NR c1 C(O)R b31 , NR c31 C(O)OR a31 , NR c31 C(O)NR c31 R d31 , NR c31 S(O) 2 R b31 , NR c31 S(O) 2 NR c31 R d31 , S(O) 2 R b31 , and S(O) 2 NR c31 R d31 ; each R 50 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 a50 , SR a50 , C(O)R b50 , C(O)NR c50 R d50 , C(O)OR a50 , OC(O)R b50 , OC(O)NR c50 R d50 , NR c50 R d50 , NR c50 C(O)R b50 , NR c50 C(O)OR a50 , NR c50 C(O)NR c50 R d50 , NR c50 S(O) 2 R b50 , NR c50 S(O) 2 NR c50 R d50 , S(O) 2 R b50 , and S(O) 2 NR c50 R d50 ; each R a1 , R b1 , 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 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl; 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; each R a2 , R b2 , 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 20 ; 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 20 ; each R a3 , R b3 , 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 3-10 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; 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 ; 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, 3, or 4 substituents independently selected from R 30 ; each R a5 , R b5 , R c5 and R d5 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; 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; each R a6 , R b6 , R c6 and R d6 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; or any R c6 and R d6 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 a7 , R b7 , 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; 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; each R a9 , R b9 , R c9 , and R d9 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; or any R c9 and R d9 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 a10 , R b10 , R c10 and R d10 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; or any R c10 and R d10 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 a20 , R b20 , R c20 and R d20 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 c20 and R d20 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 a21 , R b21 , R c21 and R d21 , 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; or any R c21 and R d21 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 a30 , R b30 , R c30 and R d30 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 31 ; or any R c30 and R d30 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 31 ; each R a31 , R b31 , R c31 and R d31 , 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; or any R c31 and R d31 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; and each R a50 , R b50 , R c50 and R d50 , 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; or any R c50 and R d50 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.
3 . The method of claim 1 , wherein the compound of Formula I, or pharmaceutically acceptable salt thereof, is a compound of Formula II:
or a pharmaceutically acceptable salt thereof, wherein:
Y is NR 5N , or C═O;
W is C═O, or C(R 8 ) 2 ;
Z is O, NR 9N , or a bond;
R 1 is selected from H, D, C 1-6 alkyl, halo, and CN;
R 2 is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a2 , and NR c2 R d2 ; wherein said C 1-6 alkyl, is optionally substituted with 1, 2, or 3 substituents independently selected from R 20 ;
Cy is selected from C 6-10 aryl and 5-10 membered heteroaryl; wherein the 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 is optionally substituted by oxo to form a carbonyl group; and wherein the C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 10 ;
R 4 is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, D, CN, OR a3 , and NR c3 R d3 ; 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 30 ;
R 5N is selected from H, C 1-6 alkyl, and C 1-6 haloalkyl; wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from R 50 ;
R 8 is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a5 , and NR c5 R d5 ;
ring A is selected from C 3-10 cycloalkyl and 4-14 membered heterocycloalkyl; wherein the 4-14 membered heterocycloalkyl 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 4-14 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group;
n is 0, 1, or 2;
each R 6 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , NR c6 R d6 , and NR c6 C(O)R b6 ;
R 7 is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a7 , and NR c7 R d7 ;
R 9N is selected from H, C 1-6 alkyl, and C 1-6 haloalkyl;
each R 10 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a10 , and NR c10 R d10 ;
each R 20 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, D, CN, OR a20 , and NR c20 R d20 ; 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 21 ;
each R 21 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl halo, D, CN, OR a21 , and NR c21 R d21 ;
each R 30 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, D, CN, OR a30 and, NR c30 R d30 ; 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 31 ;
each R 31 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a31 , and NR c31 R d31 ;
each R 50 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a50 , C(O)R b50 , C(O)NR c50 R d50 , C(O)OR a50 , NR c50 R d50 , and NR c50 C(O)R b50 ;
each R a2 , R c2 and R d2 is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl; wherein said C 1-6 alkyl, is optionally substituted with 1, 2, or 3 substituents independently selected from R 20 ;
each R a3 , R c3 and R d3 is independently selected from H, C 1-6 alkyl, 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 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 30 ;
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-, or 6-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from R 30 ;
each R a5 , R c5 and R d5 is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl;
each R a6 , R b6 , 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 a7 , R b7 , R c7 and R d7 is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl;
each R a10 , R c10 and R d10 is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl;
each R a20 , R c20 and R d20 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 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 21 ;
or any R c20 and R d20 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, or 3 substituents independently selected from R 21 ;
each R a21 , R c21 and R d21 , is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl;
each R a30 , R c30 and R d30 is independently selected from H, C 1-6 alkyl, 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 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 31 ;
or any R c30 and R d30 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, or 3 substituents independently selected from R 31 ;
each R a31 , R c31 and R d31 , is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl; and
each R a50 , R b50 , R c50 and R d50 , is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl.
4 . The method of claim 3 , wherein
Y is NR 5N , or C═O; W is C═O, or C(R 8 ) 2 ; Z is O, NR 9N , or a bond; R 1 is selected from H, D, C 1-3 alkyl, and halo; R 2 is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, halo, D, and CN; wherein said C 1-6 alkyl, is optionally substituted with 1 or 2 substituents independently selected from R 20 ; Cy is selected from C 6-10 aryl and 5-10 membered heteroaryl; wherein the 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, or 3 ring-forming heteroatoms independently selected from N and O; wherein a ring-forming carbon atom of 5-10 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 10 ; R 4 is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, OR a3 , and NR c3 R d3 ; wherein said C 1-6 alkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl, are each optionally substituted with 1, 2, or 3 substituents independently selected from R 30 ; R 5N is selected from H, C 1-6 alkyl, and C 1-6 haloalkyl; wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from R 50 ; R 8 is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, halo, D, and CN; ring A is selected from C 3-6 cycloalkyl and 4-6 membered heterocycloalkyl; wherein the 4-14 membered heterocycloalkyl has at least one ring-forming carbon atom and 1 or 2 ring-forming heteroatoms independently selected from N and O; wherein a ring-forming carbon atom of 4-6 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; n is 0, 1, or 2; each R 6 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a6 , C(O)R b6 , and NR c6 R d6 ; R 7 is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, halo, D, and CN; R 9N is selected from H, C 1-6 alkyl, and C 1-6 haloalkyl; each R 10 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a10 , and NR c10 R d10 ; each R 20 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, OR a20 , and NR c20 R d20 ; wherein said C 1-6 alkyl, phenyl, and 5-6 membered heteroaryl, are each optionally substituted with 1 or 2 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 a21 , and NR c21 R d21 ; each R 30 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, OR a30 and, NR c30 R d30 ; wherein said C 1-6 alkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl, are each optionally substituted with 1 or 2 substituents independently selected from R 31 ; each R 31 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a31 , and NR c31 R d31 ; each R 50 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a50 , C(O)NR c50 R d50 , NR c50 R d50 , and NR c50 C(O)R b50 ; each R a3 , R c3 and R d3 is independently selected from H, C 1-6 alkyl, 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 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 30 ; 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-, or 6-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from R 30 ; each R a6 , R b6 , 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 a10 , R c10 and R d10 is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl; each R a20 , R c20 and R d20 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, phenyl and 5-6 membered heteroaryl; wherein said C 1-6 alkyl, phenyl and 5-6 membered heteroaryl, are each optionally substituted with 1 or 2 substituents independently selected from R 21 ; each R a21 , R c21 and R d21 , is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl; each R a30 , R c30 and R d30 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; wherein said C 1-6 alkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl, are each optionally substituted with 1 or 2 substituents independently selected from R 31 ; or any R c30 and R d30 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 31 ; each R a31 , R c31 and R d31 , is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl; and each R a50 , R c50 and R d50 , is independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl.
5 . The method of claim 1 , wherein the compound of Formula I is a compound of Formula II′:
or a pharmaceutically acceptable salt thereof.
6 . The method of claim 1 , wherein
represents a double bond; X is CR 7 or N; Y is NR 5N or C═O; W is C═O, or C(R 8 ) 2 ; Z is O, NR 9N , or a bond; R 1 and R 2 are each independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, halo, and CN; Cy is C 6-10 aryl or 5-10 membered heteroaryl, both of which are optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ; R 3 is absent; R 4 is selected from H, C 1-6 alkyl, and OR a3 , wherein alkyl is optionally substituted one or two times with R 30 ; R 5N is H or C 1-6 alkyl; R 5 and R 3 are each independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, halo, D, and CN; ring A is 4-7 membered heterocycloalkyl; n is 1 or 2; R 6 is selected from C 1-6 alkyl, halo, D, CN, C(O)R b6 , C(O)OR a6 , and OC(O)R b6 ; R 7 is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, halo, D, and CN; R 9N is H or C 1-6 alkyl; each R 10 is independently selected from C 1-6 alkyl, halo, and OR a10 ; each R 30 is 4-10 membered heterocycloalkyl optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 31 ; each R 31 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, D, and CN; R a3 is C 1-6 alkyl optionally substituted one or two times with R 30 ; each R a6 and R b6 is independently selected from H, C 1-6 alkyl, and C 2-6 alkenyl; and R a10 is H or C 1-6 alkyl.
7 . The method of claim 1 , wherein
represents a double bond; X is CR 7 ; Y is NR 5N or C═O; W is C═O, or C(R 8 ) 2 ; Z is O, NR 9N , or a bond; R 1 and R 2 are each independently H or halo; Cy is C 6-10 aryl or 5-10 membered heteroaryl, both of which are optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ; R 3 is absent; R 4 is selected from H, C 1-6 alkyl, and OR a3 , wherein alkyl is optionally substituted one or two times with R 30 ; R 5N is H or C 1-6 alkyl; each R 5 and R 8 are H; ring A is 4-6 membered heterocycloalkyl; n is 1; R 6 is C(O)R b6 ; R 7 is halo; R 9N is H; each R 10 is independently selected from C 1-6 alkyl, halo, and OR a10 ; each R 30 is 4-10 membered heterocycloalkyl optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 31 ; each R 31 is C 1-6 alkyl; R a3 is C 1-6 alkyl optionally substituted one or two times with R 30 ; each R b6 is independently C 2-6 alkenyl; and R a10 is H or C 1-6 alkyl.
8 . The method of claim 1 , wherein the compound of Formula I or II is a compound of Formula IIa:
or a pharmaceutically acceptable salt thereof.
9 . The method of claim 1 , wherein the compound of Formula I or II is a compound of Formula IIb:
or a pharmaceutically acceptable salt thereof.
10 . The method of claim 1 , wherein the compound of Formula I or II is a compound of Formula IIc:
or a pharmaceutically acceptable salt thereof.
11 - 23 . (canceled)
24 . The method of claim 1 , wherein R 1 is H.
25 . (canceled)
26 . The method of claim 1 , wherein R 2 is selected from C 1-6 alkyl and halo.
27 . (canceled)
28 . The method of claim 1 , wherein Cy is selected from phenyl, naphthalenyl and indazolyl; wherein the phenyl, naphthalenyl and indazolyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 10 .
29 . The method of claim 1 , wherein each R 10 is independently selected from C 1-6 alkyl, halo, OR a10 .
30 . The method of claim 29 , wherein R a10 is H or C 1-6 alkyl.
31 . The method of claim 1 , wherein Cy is selected from 2-fluoro-6-hydroxyphenyl, 2-chloro-5-hydroxy-phenyl, 5-methyl-1H-indazol-4-yl, 3-methyl-1H-indazol-4-yl, and 2-fluoro-6-methoxyphenyl.
32 - 34 . (canceled)
35 . The method of claim 1 , wherein R 4 is selected from H, 4-6 membered heterocycloalkyl, and OR a3 ; wherein said 4-6 membered heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from R 30 .
36 . The method of claim 35 , wherein R 4 is selected from H, 1-(methyl-pyrrolidin-2-yl)methoxy, 1-(ethoxy)piperidine, and 3-(dimethylamino)-azetidin-1-yl.
37 - 38 . (canceled)
39 . The method of claim 1 , wherein R 5N is selected from H, C 1-6 alkyl, C 2-6 alkenyl, and C 1-6 haloalkyl.
40 - 42 . (canceled)
43 . The method of claim 1 , wherein ring A is C 3-6 cycloalkyl or 4-6 membered heterocycloalkyl; wherein the 4-6 membered heterocycloalkyl has at least one ring-forming carbon atom and 1 or 2 ring-forming heteroatoms independently selected from N and O.
44 . (canceled)
45 . The method of claim 1 , wherein n is 0, 1, or 2.
46 - 48 . (canceled)
49 . The method of claim 48 , wherein R 6 is C(O)R b6 , and R b6 is C 2-6 alkenyl.
50 . The method of claim 1 , wherein ring A-R 6 is selected from:
51 - 55 . (canceled)
56 . The method of claim 1 , wherein R 7 is halo.
57 . The method of claim 1 , wherein each R 8 is H.
58 . The method of claim 1 , wherein R 9N is H.
59 . The method of claim 1 , wherein the compound of Formula I is selected from:
1-acryloyl-9′-chloro-7′-fluoro-8′-(2-fluoro-6-hydroxyphenyl)-1′,4′-dihydro-3′ H-spiro-[piperidine-4,2′-pyrazino[2,3-c]quinolin]-3′-one; 1-acryloyl-9′-chloro-8′-(2-chloro-5-hydroxyphenyl)-7′-fluoro-1′,4′-dihydro-3′ H-spiro-[piperidine-4,2′-pyrazino[2,3-c]quinolin]-3′-one; 1-acryloyl-9′-chloro-7′-fluoro-8′-(3-methyl-1H-indazol-4-yl)-1′,4′-dihydro-3′H-spiro-[piperidine-4,2′-pyrazino[2,3-c]quinolin]-3′-one; 1-acryloyl-9′-chloro-7′-fluoro-8′-(5-methyl-1H-indazol-4-yl)-1′,4′-dihydro-3′H-spiro-[piperidine-4,2′-pyrazino[2,3-c]quinolin]-3′-one; 1-acryloyl-9′-chloro-7′-fluoro-8′-(2-fluoro-6-methoxyphenyl)-1′, 4′-dihydro-3′H-spiro-[piperidine-4,2′-pyrazino[2,3-c]quinolin]-3′-one; 1-acryloyl-9′-chloro-7′-fluoro-8′-(2-fluoro-6-hydroxyphenyl)-1′,4′-dihydro-3′H-spiro-[azetidine-3,2′-pyrazino[2,3-c]quinolin]-3′-one; 1-acryloyl-9′-chloro-7′-fluoro-8′-(5-methyl-1H-indazol-4-yl)-1′,4′-dihydro-3′H-spiro-[azetidine-3,2′-pyrazino[2,3-c]quinolin]-3′-one; 1′-acryloyl-9-chloro-7-fluoro-8-(2-fluoro-6-hydroxyphenyl)-1,4-dihydro-3H-spiro-[pyrazino[2,3-c]quinoline-2,3′-pyrrolidin]-3-one; 1′-acryloyl-9-chloro-7-fluoro-8-(5-methyl-1H-indazol-4-yl)-1,4-dihydro-3H-spiro-[pyrazino[2,3-c]quinoline-2,3′-pyrrolidin]-3-one; 1-acryloyl-9′-chloro-7′-fluoro-8′-(2-fluoro-6-hydroxyphenyl)-5′-((1-methylpyrrolidin-2-yl)-methoxy)-1′,4′-dihydro-3′H-spiro[piperidine-4,2′-pyrazino[2,3-c]quinolin]-3′-one; 1-acryloyl-9′-chloro-7′-fluoro-8′-(3-hydroxynaphthalen-1-yl)-5′-((1-methylpyrrolidin-2-yl)-methoxy)-1′,4′-dihydro-3′H-spiro[piperidine-4,2′-pyrazino[2,3-c]quinolin]-3′-one; 1-acryloyl-9′-chloro-7′-fluoro-8′-(2-fluoro-6-hydroxyphenyl)-5′-(2-(piperidin-1-yl)ethoxy)-1′,4′-dihydro-3′H-spiro[piperidine-4,2′-pyrazino[2,3-c]quinolin]-3′-one; 1-acryloyl-8′-chloro-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-4′-((1-methylpyrrolidin-2-yl)-methoxy)spiro[piperidine-4,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; 1-acryloyl-8′-chloro-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-4′-((1-methylpyrrolidin-2-yl)-methoxy)spiro[pyrrolidine-3,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; 1-acryloyl-8′-chloro-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-3′-methyl-4′-((1-methyl-pyrrolidin-2-yl)methoxy)spiro[piperidine-4,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; 1-acryloyl-9′-chloro-7′-fluoro-8′-(3-hydroxynaphthalen-1-yl)spiro[piperidine-4,2′-pyrano-[3,2-c]quinolin]-4′(3′H)-one; and 1-acryloyl-9′-chloro-7′-fluoro-8′-(2-fluoro-6-hydroxyphenyl)-5′-((1-methylpyrrolidin-2-yl)-methoxy)-1′,4′-dihydro-3′H-spiro[azetidine-3,2′-pyrazino[2,3-c]quinolin]-3′-one; or a pharmaceutically acceptable salt thereof.
60 . The method of claim 1 , wherein the compound of Formula I is selected from:
4′-(3-(dimethylamino)azetidin-1-yl)-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-8′-methylspiro[piperidine-3,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; 8′-chloro-7′-(7-chloro-3-hydroxynaphthalen-1-yl)-4′-(3-(dimethylamino)azetidin-1-yl)-6′-fluorospiro[piperidine-3,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; 8′-chloro-4′-(3-(dimethylamino)azetidin-1-yl)-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-5-azaspiro[bicyclo[2.2.1]heptane-2,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; 3-amino-8′-chloro-4′-(3-(dimethylamino)azetidin-1-yl)-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)spiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; 4-(4′-(3-(dimethylamino)azetidin-1-yl)-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-2′-oxo-2′,3′-dihydrospiro[piperidine-3,1′-pyrrolo[2,3-c]quinolin]-8′-yl)butanenitrile; 2-(4′-(3-(dimethylamino)azetidin-1-yl)-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-2′-oxo-2′,3′-dihydrospiro[piperidine-3,1′-pyrrolo[2,3-c]quinolin]-8′-yl)acetonitrile; 3-(4′-(3-(dimethylamino)azetidin-1-yl)-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-2′-oxo-2′,3′-dihydrospiro[piperidine-3,1′-pyrrolo[2,3-c]quinolin]-8′-yl)propanenitrile; 8′-(2-chlorobenzyl)-4′-(3-(dimethylamino)azetidin-1-yl)-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)spiro[piperidine-3,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; 2-((4′-(3-(dimethylamino)azetidin-1-yl)-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-2′-oxo-2′,3′-dihydrospiro[piperidine-3,1′-pyrrolo[2,3-c]quinolin]-8′-yl)methyl)benzonitrile; 4-(4′-(3-(dimethylamino)azetidin-1-yl)-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-2′,3′-dihydrospiro[piperidine-3,1′-pyrrolo[2,3-c]quinolin]-8′-yl)butanenitrile; 3-(4′-(3-(dimethylamino)azetidin-1-yl)-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-2′-oxo-2′,3′-dihydrospiro[azetidine-3,1′-pyrrolo[2,3-c]quinolin]-8′-yl)propanenitrile; 4-(4′-(3-(dimethylamino)azetidin-1-yl)-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-2′-oxo-2′,3′-dihydrospiro[pyrrolidine-3,1′-pyrrolo[2,3-c]quinolin]-8′-yl)butanenitrile; 4-(4′-(3-(dimethylamino)azetidin-1-yl)-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-2′-oxo-2′,3′-dihydrospiro[morpholine-2,1′-pyrrolo[2,3-c]quinolin]-8′-yl)butanenitrile; 4-(6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-4′-(((S)-1-methylpyrrolidin-2-yl)methoxy)-2′-oxo-2′,3′-dihydrospiro[piperidine-3,1′-pyrrolo[2,3-c]quinolin]-8′-yl)butanenitrile; 4-(6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-3′-methyl-4′-(((S)-1-methylpyrrolidin-2-yl)methoxy)-2′-oxo-2′,3′-dihydrospiro[piperidine-3,1′-pyrrolo[2,3-c]quinolin]-8′-yl)butanenitrile; 4-(6′-fluoro-3′-(2-hydroxyethyl)-7′-(3-hydroxynaphthalen-1-yl)-4′-(((S)-1-methylpyrrolidin-2-yl)methoxy)-2′-oxo-2′,3′-dihydrospiro[piperidine-3,1′-pyrrolo[2,3-c]quinolin]-8′-yl)butanenitrile; 4-(6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-3′-isopentyl-4′-(((S)-1-methylpyrrolidin-2-yl)methoxy)-2′-oxo-2′,3′-dihydrospiro[piperidine-3,1′-pyrrolo[2,3-c]quinolin]-8′-yl)butanenitrile; 4-(3′-(cyanomethyl)-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-4′-(((S)-1-methylpyrrolidin-2-yl)methoxy)-2′-oxo-2′,3′-dihydrospiro[piperidine-3,1′-pyrrolo[2,3-c]quinolin]-8′-yl)butanenitrile; and 2-(8′-(3-cyanopropyl)-6′-fluoro-7′-(3-hydroxynaphthalen-1-yl)-4′-(((S)-1-methylpyrrolidin-2-yl)methoxy)-2′-oxospiro[piperidine-3,1′-pyrrolo[2,3-c]quinolin]-3′(2′F)-yl)acetamide; or a pharmaceutically acceptable salt thereof.
61 - 66 . (canceled)
67 . The method of claim 1 , wherein the cancer is selected from carcinomas, hematological cancers, sarcomas, and glioblastoma.
68 . The method of claim 67 , wherein the hematological cancer is selected from myeloproliferative neoplasms, myelodysplastic syndrome, chronic and juvenile myelomonocytic leukemia, acute myeloid leukemia, acute lymphocytic leukemia, and multiple myeloma.
69 . The method of claim 67 , wherein the carcinoma is selected from pancreatic, colorectal, lung, bladder, gastric, esophageal, breast, head and neck, cervical, skin, and thyroid.
70 . (canceled)Join the waitlist — get patent alerts
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