US 12,258,327 B2
5-membered heteroaryl-containing aminopyridine compounds as EGFR inhibitors
Byoungmoon Lee, Hwaseong-si (KR); Hyunjoo Lee, Suwon-si (KR); Gyu Jin Lee, Yongin-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); James Campbell Robertson, Spring House, PA (US); Jaekyoo Lee, North Andover, MA (US); Paresh Devidas Salgaonkar, Lexington, MA (US); Byung-Chul Suh, Lexington, MA (US); Jong Sung Koh, Cambridge, MA (US); and So Young Hwang, Lexington, MA (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. 17/822,443.
Claims priority of provisional application 63/237,653, filed on Aug. 27, 2021.
Prior Publication US 2023/0085912 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)] 25 Claims
 
1. A compound of formula (I) or a pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
wherein
X1 and X2 are, independently each other, —CH═ or —N═, with the proviso that X1 and X2 cannot be —N═ at the same time,
X3, X4, and X5 are, independently each other, —CH═ or —N═, with the proviso that X3, X4, and X5 cannot be —CH═ at the same time,
R1 is -A or -A-(R1A)m,
A is 5-membered heteroaryl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridinyl, or 6,7-dihydropyrrolo[1,2-a]imidazolyl,
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, C1-3 alkoxy, C3-6 cycloalkyl, —NHC1-6 alkyl, —N(C1-6 alkyl)2, and 4-7 membered heterocyclyl optionally or independently substituted by one or more substituents selected from the group consisting of OH, halogen, and C1-6 alkyl;
C3-6 cycloalkyl;
C1-3 alkoxy optionally substituted by one or more substituents selected from the group consisting of OH, halogen, —N(C1-6 alkyl)2, and 3-7 membered heterocyclyl optionally or independently substituted by one or more substituents selected from the group consisting of halogen and C1-6 alkyl;
—NHC1-6 alkyl 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 1 or 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 3,
o is an integer of 1 to 3,
B is selected from the group consisting of C3-8 cycloalkyl; 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, —N(C1-6alkyl)(C1-6haloalkyl), —NHC(O)C1-6alkyl, —C(O)NHC1-6alkyl, —C(O)N(C1-6alkyl)2, 3-7 membered heterocyclyl optionally substituted by one or more halogens, 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;
4-7 membered heterocyclyl; and
═O,
R3 is Y-Q or Y-Q-(R3A)p,
Y is —NH— or bond,
Q is selected from the group consisting of ethynyl; 4-7 membered heterocyclyl; 2,3-dihydropyrido[2,3-b][1,4]oxazinyl; 3,4-dihydropyrano[2,3-b]pyridinyl; C6-10 aryl; and 5 membered heteroaryl,
p is an integer of 1 to 3,
R3A is independently selected from the group consisting of
OH;
halogen;
C1-3alkoxy;
C1-6alkyl optionally or independently substituted by one or more substituents selected from the group consisting of OH, halogen, C1-3alkoxy, C3-6cycloalkyl, and S(O)2C1-6alkyl;
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, halogen, and C1-6alkyl, and
R4 is selected from the group consisting of H, halogen and C1-6alkyl.