US 11,999,718 B2
Pyrazole derivatives
Soo Jin Lee, Suwon-si (KR); Sung Hwan Moon, Suwon-si (KR); Sooho Ban, Suwon-si (KR); Eunsil Lee, Suwon-si (KR); Eun Jung Shin, Suwon-si (KR); and Yoo-Kyung Goh, Suwon-si (KR)
Assigned to APTABIO THERAPEUTICS INC., Yongin-si (KR)
Filed by Aptabio Therapeutics Inc., Yongin-si (KR)
Filed on Jan. 6, 2023, as Appl. No. 18/150,955.
Application 18/150,955 is a continuation of application No. PCT/KR2022/002802, filed on Feb. 25, 2022.
Claims priority of application No. 10-2021-0025694 (KR), filed on Feb. 25, 2021.
Prior Publication US 2023/0234940 A1, Jul. 27, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 401/14 (2006.01); A61P 1/16 (2006.01); A61P 11/00 (2006.01); A61P 35/00 (2006.01); A61P 39/06 (2006.01); C07D 231/54 (2006.01); C07D 401/04 (2006.01); C07D 401/12 (2006.01); C07D 403/04 (2006.01); C07D 405/04 (2006.01); C07D 413/04 (2006.01); C07D 417/04 (2006.01); C07D 471/04 (2006.01); C07D 495/04 (2006.01)
CPC C07D 401/14 (2013.01) [A61P 1/16 (2018.01); A61P 11/00 (2018.01); A61P 35/00 (2018.01); A61P 39/06 (2018.01); C07D 231/54 (2013.01); C07D 401/04 (2013.01); C07D 401/12 (2013.01); C07D 403/04 (2013.01); C07D 405/04 (2013.01); C07D 413/04 (2013.01); C07D 417/04 (2013.01); C07D 471/04 (2013.01); C07D 495/04 (2013.01)] 12 Claims
 
1. A compound of Chemical formula I below, or a stereoisomer thereof, a solvate thereof, an isotopic variant thereof, a tautomer thereof, or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
in the formula,
A is a substituted or unsubstituted 5-membered to 20-membered heteroaryl or substituted or unsubstituted C5-C20 aryl; and
then, the 5-membered to 20-membered heteroaryl or C6-C20 aryl of A are unsubstituted, or are substituted with 1, 2, 3 or 4 kinds of substituents consisting of cyano, halo, C1-C6 haloalkyl, nitro, —C(═O)R1, —C(═O)OR1, —NH—C(═O)R1, C1-C10 alkoxy group, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted amino, substituted or unsubstituted C5-C20 aryl, substituted or unsubstituted 5-membered to 20-membered heteroaryl and substituted or unsubstituted 5-membered to 20-membered heterocycloalkyl, and then, the R1 is hydrogen, heavy hydrogen, or C1-C10 alkyl,
two or more adjacent substituents of the 5-membered to 20-membered heteroaryl or C6-C20 aryl of A are combined with each other to form an unsubstituted 5-membered to 10-membered heteroaryl ring comprising 0, 1, 2 or 3 heteroatoms selected from N, O and S or a C5-C10 aryl ring; and
R is hydrogen, heavy hydrogen, cyano, halo, nitro, C1-C6 haloalkyl, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C5-C20 aryl, substituted or unsubstituted 5-membered to 20-membered heteroaryl, or —C(═O)R2, and then, the R2 is C3-C8 cycloalkyl, C1-C10 alkyl, C2-C10 alkenyl, or C6-C10 aryl; and
B is -N(K)M or substituted or unsubstituted 5-membered to 20-membered heteroaryl or substituted or unsubstituted 5-membered to 20-membered heterocycloalkyl; and
K is hydrogen, heavy hydrogen, cyano, halo, nitro, C1-C6 haloalkyl, substituted or unsubstituted C1-C10 alkyl, unsubstituted C1-C10 alkoxy, —C(═O)R′, —C(═O)OR′, —SO2—R″, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C6-C20 aryl C1-C10 alkyl, substituted or unsubstituted 5-membered to 20-membered heteroaryl or substituted or unsubstituted 5-membered to 20-membered heteroaryl C1-C10 alkyl;
M is cyano, halo, nitro, C1-C6 haloalkyl, substituted or unsubstituted C1-C10 alkyl, unsubstituted C1-C10 alkoxy, —C(═O)R′, —C(═O)OR′, —SO2-R″, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C6-C20 aryl C1-C10 alkyl, substituted or unsubstituted 5-membered to 20-membered heteroaryl or substituted or unsubstituted 5-membered to 20-membered heteroaryl C1-C10 alkyl;
wherein the C1-C10 alkyl is unsubstituted, or substituted with 1, 2, 3 or 4 kinds of substituents selected from the group consisting of heavy hydrogen, halo, hydroxy, cyano, nitro, carboxyl, substituted or unsubstituted amino, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C1-C10 haloalkyl, substituted or unsubstituted C1-C10 hydroxyalkyl, substituted or unsubstituted C3-C8 cycloalkyl, C1-C10 alkoxy, C1-C10 alkylsulfonyl, C5-C20 arylsulfonyl, C5-C20 aryloxy, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 5-membered to 20-membered heteroaryl and substituted or unsubstituted 5-membered to 20-membered heterocycloalkyl; and
the C3-C8 cycloalkyl is unsubstituted, or substituted with 1, 2, 3 or 4 kinds of substituents selected from the group consisting of heavy hydrogen, halogen, cyano, nitro, carboxyl, substituted or unsubstituted amino, substituted or unsubstituted C6-C20 aryl or 5-membered to 20-membered heteroaryl, C1-C10 alkoxy and C1-C10 haloalkyl; and
the 5-membered to 20-membered heteroaryl, 5-membered to 20-membered heterocycloalkyl, or C6-C20 aryl is unsubstituted, or substituted with 1, 2, 3 or 4 kinds of substituents selected from the group consisting of heavy hydrogen, halo, cyano, nitro, —C(═O)R′, —C(═O)OR′, —NH—C(═O)R″, substituted or unsubstituted amino, substituted or unsubstituted C1-C10 alkyl, unsubstituted C1-C10 alkoxy, substituted or unsubstituted C1-C10 haloalkyl, substituted or unsubstituted C1-C10 hydroxyalkyl, substituted or unsubstituted C1-C10 alkylsulfonyl, substituted or unsubstituted C5-C20 arylsulfonyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 cycloalkyl C1-C10 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C6-C20 aryl C1-C10 alkyl, substituted or unsubstituted 5-membered to 12-membered heterocycloalkyl, substituted or unsubstituted C1-C10 alkyl C3-C8 cycloalkyl and substituted or unsubstituted C1-C10 alkyl 5-membered to 20-membered heterocycloalkyl, and
then, the R′ and R″ are each independently hydrogen, heavy hydrogen, substituted or unsubstituted amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C3-Cg cycloalkyl, substituted or unsubstituted C6-C10 aryl or substituted or unsubstituted C6-C10 aryl C1-C6 alkyl, and then, the C2-C6 alkenyl or C2-C6 alkynyl is unsubstituted or substituted with 1, 2, 3 or 4 kinds of mono C1-C6 alkylamine or di C1-C6 alkylamine; and
the substituted amino group is substituted with 1 kind or 2 kinds of C1-C10 alkyl, C6-C10 aryl or C6-C10 aryl C1-C6 alkyl groups; and
the heteroatom of the heterocycloalkyl or heteroaryl ring is one or more kinds selected from N, S and O.