US 11,753,411 B2
Substituted pyrazolo[1,5-a]pyrimidines as TYK2 pseudokinase ligands
Raju Mohan, Encinitas, CA (US); John Nuss, Encinitas, CA (US); Jason Harris, Encinitas, CA (US); and Shendong Yuan, Encinitas, CA (US)
Assigned to VENTYX BIOSCIENCES, INC., Encinitas, CA (US)
Filed by Ventyx Biosciences, Inc., Encinitas, CA (US)
Filed on Nov. 5, 2020, as Appl. No. 17/90,805.
Claims priority of provisional application 62/933,179, filed on Nov. 8, 2019.
Claims priority of provisional application 63/046,514, filed on Jun. 30, 2020.
Prior Publication US 2021/0139486 A1, May 13, 2021
Int. Cl. A61K 31/519 (2006.01); C07D 487/04 (2006.01); C07D 519/00 (2006.01)
CPC C07D 487/04 (2013.01) [C07D 519/00 (2013.01)] 19 Claims
 
1. A compound having Formula (I′):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein:
X is N;
Y is C1-C6alkyl, C3-C6cycloalkyl, C2-C9heterocycloalkyl, C6-C10aryl, or C2-C9heteroaryl, wherein the C1-C6alkyl, C3-C6cycloalkyl, C2-C9heterocycloalkyl, C6-C10aryl, or C2-C9heteroaryl is optionally substituted by 1, 2, 3, or 4 independently selected R7 substituents; or
Y is

OG Complex Work Unit Chemistry
L1 is a bond, —CH2NR9—, —C(O)—, —NR9—, —NR9CH2—, or —O—;
R1 is C3-C6cycloalkyl, wherein the C3-C6cycloalkyl is substituted by 1, 2, or 3 independently selected R13 substituents;
R2 is hydrogen, deuterium, C1-C6alkyl, or C1-C6deuteroalkyl;
R3 is hydrogen, deuterium, C1-C6alkyl, or C1-C6deuteroalkyl;
R4 is hydrogen, deuterium, C1-C6alkyl, or C1-C6deuteroalkyl;
R5 is hydrogen or C1-C6alkyl;
R6 is hydrogen, deuterium, C1-C6alkyl, or C1-C6deuteroalkyl;
each R7 is independently deuterium, halogen, —CN, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6haloalkyl, C1-C6heteroalkyl, —C(O)R11, —C(O)NR10R10, —C(O)OR10, —NR10R10, —NR10C(O)R11, —NR10S(O)2R11, —OR10, ═O, —S(O)2R11, —S(O)2NR10R10, C3-C6cycloalkyl, C2-C9heterocycloalkyl, C6-C10aryl, or C2-C9heteroaryl, wherein each C3-C6cycloalkyl, C2-C9heterocycloalkyl, C6-C10aryl, and C2-C9heteroaryl is optionally and independently substituted by 1, 2, or 3 substituents independently selected from the group consisting of halogen, C1-C6alkyl, C1-C6haloalkyl, —C(O)NR12R12, —C(O)OR12, —NR12R12, —OR12, C2-C9heterocycloalkyl, and C2-C9heteroaryl; or two R7, together with the carbon atom(s) to which they are attached, form a 4-, 5-, or 6-membered cycloalkyl or a 5-, 6-, or 7-membered heterocycloalkyl;
R8 is hydrogen, deuterium, halogen, C1-C6alkyl, or C1-C6deuteroalkyl;
R9 is hydrogen or C1-C6alkyl;
each R10 is independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6heteroalkyl, or phenyl, wherein each phenyl is optionally and independently substituted by 1, 2, or 3 substituents independently selected from the group consisting of halogen, C1-C6alkyl, C1-C6haloalkyl, —C(O)NR12R12, —C(O)OR12, —NR12R12, —OR12, C2-C9heterocycloalkyl, and C2-C9heteroaryl;
each R11 is independently C1-C6alkyl or C1-C6heteroalkyl;
each R12 is independently hydrogen, C1-C6alkyl, or C1-C6haloalkyl;
each R13 is independently halogen, —CN, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6haloalkyl, C1-C6heteroalkyl, —C(O)R11, —C(O)NR10R10, —C(O)OR10, —NR10R10, —NR10C(O)R11, —NR10S(O)2R11, —OR10, ═O, —S(O)2R11, —S(O)2NR10R10, C3-C6cycloalkyl, C2-C9heterocycloalkyl, C6-C10aryl, or C2-C9heteroaryl, wherein each C3-C6cycloalkyl, C2-C9heterocycloalkyl, C6-C10aryl, and C2-C9heteroaryl is optionally and independently substituted by 1, 2, or 3 substituents independently selected from the group consisting of halogen, C1-C6alkyl, C1-C6haloalkyl, —C(O)NR12R12, —C(O)OR12, —NR12R12, —OR12, C2-C9heterocycloalkyl, and C2-C9heteroaryl; and
n is 0, 1, 2, 3, or 4.
 
16. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof.