US 12,258,328 B2
6-membered heteroaryl-containing aminopyridine compounds as EGFR inhibitors
Hyunjoo Lee, Suwon-si (KR); Su Bin Choi, Hwaseong-si (KR); Misong Kim, Suwon-si (KR); Young Ae Yoon, Seongnam-si (KR); Kwan Hoon Hyun, Incheon (KR); Jae Young Sim, Yongin-si (KR); Marian C. Bryan, Spring House, PA (US); Scott Kuduk, Spring House, PA (US); and James Campbell Robertson, Spring House, PA (US)
Assigned to YUHAN CORPORATION, Seoul (KR); and JANSSEN BIOTECH, INC., Horsham, PA (US)
Filed by YUHAN CORPORATION, Seoul (KR); and JANSSEN BIOTECH, INC., Horsham, PA (US)
Filed on Aug. 26, 2022, as Appl. No. 17/822,445.
Claims priority of provisional application 63/237,653, filed on Aug. 27, 2021.
Prior Publication US 2023/0090406 A1, Mar. 23, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 401/14 (2006.01); C07D 413/14 (2006.01); A61K 31/506 (2006.01); A61P 35/00 (2006.01); A61P 37/00 (2006.01); C07D 405/14 (2006.01)
CPC C07D 401/14 (2013.01) [C07D 413/14 (2013.01)] 20 Claims
 
1. A compound of formula (I) or a pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
wherein
X1 and X2 are —CH═,
X3, and X4 are —N═,
R1 is -A or -A-(R1A)m,
A is 6-10 membered heteroaryl,
R1A is independently selected from the group consisting of
OH;
halogen;
cyano;
C1-6alkyl optionally substituted by one or more substituents selected from the group consisting of OH, halogen, C1-3alkoxy, C3-6cycloalkyl, —NHC1-6alkyl, —N(C1-6alkyl)2, and 4-7 membered heterocyclyl optionally or independently substituted by one or more substituents selected from the group consisting of OH, halogen, and C1-6alkyl;
C3-6cycloalkyl;
C1-3alkoxy optionally substituted by one or more substituents selected from the group consisting of OH, halogen, —N(C1-6alkyl)2, and 3-7 membered heterocyclyl optionally or independently substituted by one or more substituents selected from the group consisting of halogen and C1-6alkyl;
—NHC1-6alkyl optionally substituted by one or more substituents selected from the group consisting of OH, halogen, —N(C1-6alkyl)2 and 3-7 membered heterocyclyl optionally substituted by one or more substituents selected from the group consisting of OH, halogen, and C1-6alkyl;
—NHC3-6cycloalkyl optionally substituted by one or more substituents selected from the group consisting of OH, halogen and C1-6alkyl optionally substituted by OH;
—NH 3-7 membered heterocyclyl optionally substituted by one or more substituents selected from the group consisting of OH, halogen, and C1-6alkyl;
—N(C1-6alkyl)2 optionally substituted by one or more substituents selected from the group consisting of OH and halogen;
—NHC(O)C1-6alkyl optionally substituted by one or more substituents selected from the group consisting of OH and halogen;
—NHC(O)C3-6cycloalkyl optionally substituted by one or more substituents selected from the group consisting of OH and halogen;
—O-4-7 membered heterocyclyl optionally or independently substituted by one or more substituents selected from the group consisting of C1-6alkyl and C1-6haloalkyl;
4-7 membered heterocyclyl optionally or independently substituted by one or more substituents selected from the group consisting of OH, halogen, C1-6alkyl, C1-3alkoxy, C1-6hydroxyalkyl, and C1-6haloalkyl;
—S(O)2C1-6alkyl optionally substituted by one or more halogens;
—S(O)2C3-6cycloalkyl optionally substituted by one or more halogens;
—S(O)2N(C1-6alkyl)2 optionally substituted by one or more halogens;
—S(O)2-3-7 membered heterocyclyl optionally substituted by one or more substituents selected from the group consisting of OH, halogen, and C1-6alkyl;
—C(O)OC1-6alkyl;
—C(O)C1-6alkyl; and
—C(O)-3-7 membered heterocyclyl optionally substituted by one or more substituents selected from the group consisting of OH, halogen, and C1-6alkyl,
m is an integer of 0 to 2,
R2 is —XC1-6alkyl optionally substituted by one or more substituents selected from the group consisting of OH, halogen, and —N(C1-6alkyl)2; —X(CH2)n—B or —X(CH2)n—B—(R2A)o,
X is —NH—, —O—, bond or —C≡C—,
n is an integer of 0 to 2,
is an integer of 0 to 3,
B is selected from the group consisting of C3-8cycloalkyl, C6-10 aryl; 4-11 membered heterocyclyl; and 5-6 membered heteroaryl,
R2A is independently selected from the group consisting of
OH;
halogen;
NH2;
C1-6alkyl optionally substituted by one or more substituents selected from the group consisting of OH, NH2, halogen, C3-6cycloalkyl, C1-3alkoxy, —NHC1-6alkyl, —NHC1-6hydroxyalkyl, —NHC1-6haloalkyl, —NHC3-6cycloalkyl, —N(C1-6alkyl)2, —N(C1-6haloalkyl)2, —NHC(O)C1-6alkyl, —C(O) NHC1-6alkyl, —C(O)N(C1-6alkyl)2, 3-7 membered heterocyclyl and 5-6 membered heteroaryl;
C3-6cycloalkyl;
C1-3alkoxy optionally substituted by one or more halogens;
—C(O) NHC1-6alkyl optionally substituted by one or more substituents selected from the group consisting of OH and halogen;
—C(O)N(C1-6alkyl)2 optionally substituted by one or more substituents selected from the group consisting of OH and halogen;
—NHC1-6alkyl optionally substituted by one or more substituents selected from the group consisting of OH, halogen, —NHC1-6alkyl, —N(C1-6alkyl)2, 3-7 membered heterocyclyl optionally substituted by halogen or —N(C1-6alkyl)2;
—N(C1-6alkyl)2 where C1-6alkyl is optionally substituted by one or more halogens;
—NH-4-7 membered heterocyclyl optionally substituted by C1-6alkyl; and
4-7 membered heterocyclyl,
R3 is Y-Q or Y-Q-(R3A)p,
Y is —NH— or bond,
Q is selected from the group consisting of acetylene; dihydropyranopyridinyl; 4-7 membered heterocyclyl; C6-10 aryl; and 5-10 membered heteroaryl,
p is an integer of 0 to 2,
R3A is independently selected from the group consisting of
OH;
halogen;
C1-3alkoxy;
C1-6alkyl optionally substituted by one or more substituents selected from the group consisting of OH, halogen, C3-6cycloalkyl, S(O)2C1-6alkyl, and C1-3alkoxy;
C2-6alkenyl;
C3-6cycloalkyl;
4-7 membered heterocyclyl;
—C(O)C1-6alkyl;
—C(O)N(C1-6alkyl)2;
—S(O)2C1-6alkyl optionally substituted by one or more halogens;
—S(O)2C2-6alkenyl;
—S(O)2C3-6cycloalkyl optionally substituted by one or more halogens;
—S(O)2N(C1-6alkyl)2; and
—S(O)2-4-7 membered heterocyclyl optionally substituted by one or more substituents selected from the group consisting of OH and halogen, and
R4 is selected from the group consisting of H, halogen and C1-6alkyl.