US2023192664A1PendingUtilityA1
Pyridazinones as parp7 inhibitors
Est. expiryApr 30, 2038(~11.8 yrs left)· nominal 20-yr term from priority
C07D 495/04C07D 417/14C07D 401/14A61P 35/00C07D 413/14C07D 403/14C07D 487/04C07D 405/14C07D 403/04C07D 487/08C07D 487/10C07D 451/02C07D 471/04C07D 403/12C07D 471/10C07D 417/12A61K 31/506C07D 401/12C07D 471/08A61K 31/5377A61K 31/501A61K 31/496
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Claims
Abstract
The present invention relates to pyridazinones and related compounds which are inhibitors of PARP7 and are useful in the treatment of cancer.
Claims
exact text as granted — not AI-modified1 - 443 . (canceled)
444 . A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
X is Cl, Br, CH 3 , CF 3 , CN, OCH 3 , ethyl, cyclopropyl, SCH 3 , or isopropyl;
A is a group having the formula (A-1):
Y 1 , Y 2 , and Y 3 are each independently selected from O, S, NR Y , C(═O), C(═O)O, C(═O)NR, S(═O), S(═O) 2 , S(═O)NR, S(═O) 2 NR Y or NR Y C(═O)NR Y , wherein each R Y is independently H or C 1-4 alkyl;
L is C 1-3 alkylene, O, S, NR Y , C(═O), C(═O)O, C(═O)NR Y , S(═O), S(═O)NR Y , or NR Y C(═O)NR Y ;
Z is H, Cy Z , halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl of Z are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Cy Z , halo, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ;
Cy Z is selected from C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, each optionally substituted by 1, 2, 3, or 4 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, NO 2 , OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )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 , and S(O) 2 NR c1 R d1 , wherein the alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are optionally substituted with 1, 2, or 3 substituents independently selected from halo, CN, NO 2 , OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R a1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R a1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )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 , and S(O) 2 NR c1 R d1 ;
Ring D is a monocyclic or polycyclic 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, or 3 groups independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )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)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 , wherein the C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, or 3 groups independently selected from halo, CN, NO 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , C(═NR e2 )NR e2 R d2 , NR c2 C(═NR e2 )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)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 ;
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 are each independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl of said R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;
or R 1 and R 3 together with the carbon atoms to which they are attached form a C 5-10 cycloalkyl ring or a 5-10 membered heterocycloalkyl ring, each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;
or R 3 and R 5 together with the carbon atoms to which they are attached form a C 5-10 cycloalkyl ring or a 5-10 membered heterocycloalkyl ring, each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;
or R 7 and R 9 together with the carbon atoms to which they are attached form a C 5-10 cycloalkyl ring or a 5-10 membered heterocycloalkyl ring, each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;
or R 9 and R 11 together with the carbon atoms to which they are attached form a C 5-10 cycloalkyl ring or a 5-10 membered heterocycloalkyl ring, each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;
or R 5 and R 7 together with the carbon atoms to which they are attached and together with Y 2 form a 5-10 membered heterocycloalkyl ring optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;
or R 1 and R 3 together form a double bond between the carbon atoms to which they are attached;
or R 3 and R 5 together form a double bond between the carbon atoms to which they are attached;
or R 7 and R 9 together form a double bond between the carbon atoms to which they are attached;
or R 9 and R 11 together form a double bond between the carbon atoms to which they are attached;
or R 9 , R 10 , R 11 , and R 12 together form a triple bond between the carbon atoms to which they are attached;
each R a , R b , R c , R d , R a1 , R b1 , R c1 , R d1 , R a2 , R b2 , R c2 , R d2 , R a3 , R b3 , R c3 , and R d3 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl of said R a , R b , R c , R d , R a1 , R b1 , R c1 , R d1 , R a2 , R b2 , R c2 , R d2 , R a3 , R b3 , R c3 , and R d3 is optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, 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)NR c7 R d7 NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR 7 )NR c3 R d7 S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 NR c7 S(O) 2 NR c7 R d7 and S(O) 2 NR c7 R d7 ;
or R c and R d together with the N atom to which they are attached form a 4-7 membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from CN, halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, 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)NR c7 R d7 NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR 7 )NR c3 R d7 S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 NR c7 S(O) 2 NR c7 R d7 and S(O) 2 NR c7 R d7 ;
or R c1 and R d2 together with the N atom to which they are attached form a 4-7 membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from CN, halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, 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)NR c7 R d7 NR c7 C(O)OR a7 , C(═NR 7 )NR c7 R d7 , NR c7 C(═NR 7 )NR c3 R d7 S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 NR c7 S(O) 2 NR c7 R d7 and S(O) 2 NR c7 R d7 ;
or R c2 and R d2 together with the N atom to which they are attached form a 4-7 membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from CN, halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, 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)NR c7 R d7 NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 NR c7 S(O) 2 NR c7 R d7 and S(O) 2 NR c7 R d7 ;
or R c3 and R d3 together with the N atom to which they are attached form a 4-7 membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from CN, halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, 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)NR c7 R d7 NR c7 C(O)OR a7 , C(═NR 7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c3 R d7 S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 NR c7 S(O) 2 NR c7 R d7 and S(O) 2 NR c7 R d7 ;
R a7 , R b7 , R c7 , and R d7 are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2 -6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy;
each R e , R e1 , R e2 , R e3 , and R e7 is independently selected from H, C 1-4 alkyl, and CN;
a is 0 or 1;
m is 0 or 1;
n is 0 or 1;
p is 0 or 1;
q is 0 or 1;
r is 0 or 1;
wherein any aforementioned heteroaryl or heterocycloalkyl group comprises 1, 2, 3, or 4 ring-forming heteroatoms independently selected from O, N, and S; and
wherein one or more ring-forming C or N atoms of any aforementioned heterocycloalkyl group is optionally substituted by an oxo (═O) group.
445 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof wherein A is group having the formula (A-1a):
446 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof wherein A is group having the formula (A-1b):
447 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof wherein A is group having the formula (A-1c):
wherein Z 1 and Z 2 are each independently selected from N and CH, and wherein R is CN, Cl, or CF 3 .
448 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof wherein A is group having the formula (A-1d):
wherein Z 1 and Z 2 are each independently selected from N and CH, and wherein R is CN, Cl, or CF 3 .
449 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof wherein L is NR Y or O.
450 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein X is CF 3 , CH 3 , CN, Cl or Br.
451 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein Y 1 is NR Y , O, or S.
452 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein Y 1 is NR Y .
453 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein Y 2 is NR Y , O, or S.
454 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein Y 2 is O.
455 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein Y 3 is C(═O).
456 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein Y 3 is C(═O) or S(═O) 2 .
457 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R Y is H or C 1-4 alkyl.
458 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein Z is H, Cy Z , halo, C 1-6 alkyl, C 1-6 haloalkyl, CN, NO 2 , OR a , C(O)R b , C(O)NR c R d , C(O)OR a , NR c R d , and NR c C(O)R b ; wherein said C 1-6 alkyl and C 1-6 haloalkyl of Z are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Cy Z , halo, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , and NR c C(O)R b .
459 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein Z is Cy Z .
460 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein Cy Z is 5-10 membered heteroaryl, optionally substituted by CN, C 1-6 alkyl, C 1-6 haloalkyl, halo, or NR c1 R d1 wherein C 1-6 alkyl is optionally substituted with CN or NR c1 R d1 .
461 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein Cy Z is pyridinyl or pyrimidinyl, each optionally substituted by CN, CF 3 , or Cl.
462 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein Ring D is a monocyclic or polycyclic 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, or 3 groups independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, CN, NO 2 , OR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , NR c2 R d2 , NR c2 C(O)R b2 , wherein the C 1-6 alkyl is optionally substituted with 1, 2, or 3 groups independently selected from halo, CN, NO 2 , OR a2 , C(O)R b2 , NR c2 R d2 , and NR c2 C(O)R b2 .
463 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein Ring D is a monocyclic 4-10 membered heterocycloalkyl group.
464 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein Ring D is piperazinyl, dihydropyridazinyl, diazepanyl, pyrrolidinyl, or hexahydropyrrolo[3,2-b]pyrrol-1(2H)-yl.
465 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 1 is H, halo, OR a, C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, or 4-10 membered heterocycloalkyl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 6-10 aryl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl or 4-10 membered heterocycloalkyl-C 1-4 alkyl is optionally substituted with OR a3 or NR c3 R d3 .
466 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 1 is C 1-6 alkyl, optionally substituted with OR a3 .
467 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 1 is H.
468 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 2 is H, halo, OR a3 , C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 6-10 aryl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl is optionally substituted with OR a3 or NR c3 R d3 .
469 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 2 is H.
470 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 3 is H, halo, OR a3 , C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 6-10 aryl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl is optionally substituted with OR a3 or NR c3 R d3 .
471 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 3 is H.
472 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 4 is H, halo, OR a3 , C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 6-10 aryl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl is optionally substituted with OR a3 or NR c3 R d3 .
473 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 4 is H.
474 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 5 is H, halo, OR a, C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 6-10 aryl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl is optionally substituted with OR a3 or NR a3 R d3 .
475 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 5 is H.
476 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 6 is H, halo, OR a, C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 6-10 aryl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl is optionally substituted with OR a3 or NR a3 R d3 .
477 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 6 is H.
478 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 7 is H, halo, OR a3 , C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 6-10 aryl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl is optionally substituted with OR a3 or NR c3 R d3 .
479 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 7 is C 1-6 alkyl.
480 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 8 is H, halo, OR a3 , C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl is optionally substituted with OR a3 or NR c3 R d3 .
481 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 8 is H.
482 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 9 is H, halo, OR a, C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl is optionally substituted with OR a3 or NR c3 R d3 .
483 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 9 is H.
484 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 10 is H, halo, OR a3 , C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl is optionally substituted with OR a3 or NR c3 R d3 .
485 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 10 is H.
486 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 11 is H, halo, OR a3 , C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl is optionally substituted with OR a3 or NR c3 R d3 .
487 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 11 is H.
488 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 12 is H, halo, OR a3 , C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, or C 6-10 aryl-C 1-4 alkyl is optionally substituted with OR a3 or NR c3 R d3 .
489 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 12 is H.
490 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 3 and R 5 together with the carbon atoms to which they are attached form a C 5-10 cycloalkyl ring or a 5-10 membered heterocycloalkyl ring, each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 .
491 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 3 and R 5 together with the carbon atoms to which they are attached form a C 5-10 cycloalkyl ring or a 5-10 membered heterocycloalkyl ring.
492 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 5 and R 7 together with the carbon atoms to which they are attached and together with Y 2 form a 5-10 membered heterocycloalkyl ring optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 .
493 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, wherein R 5 and R 7 together with the carbon atoms to which they are attached and together with Y 2 form a 5-10 membered heterocycloalkyl ring.
494 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, having Formula IIa:
495 . The compound of claim 444 , or a pharmaceutically acceptable salt thereof, having Formula IIb:Join the waitlist — get patent alerts
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