US 11,981,658 B2
Substituted 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); Sol Park, Yongin-si (KR); Heejun Kim, Hwaseong-si (KR); Misong Kim, Suwon-si (KR); Young Ae Yoon, Seongnam-si (KR); Kwan Hoon Hyun, Icheon (KR); Tae Kyun Kim, Hwaseong-si (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. 17/822,450.
Claims priority of provisional application 63/237,647, filed on Aug. 27, 2021.
Prior Publication US 2023/0086884 A1, Mar. 23, 2023
Int. Cl. C07D 401/14 (2006.01)
CPC C07D 401/14 (2013.01) 39 Claims
 
1. A compound of formula (I) or a pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
Wherein
R1 is selected from the group consisting of
—H;
—Si(C1-6 alkyl)3;
C1-6 alkyl optionally or independently substituted by one or more substituents selected from the group consisting of OH, halogen, C1-3alkoxy, C3-6 cycloalkyl, —NHC1-6 alkyl, —NHC1-6haloalkyl, —N(C1-6 alkyl)2, —N(C1-6 haloalkyl)2, —NHC(O)C1-6 alkyl, —NHC(O)C1-6 haloalkyl, —NHC(O)C3-6 cycloalkyl, —NHC(O)-4-7 membered heterocyclic, —C(O)-4-7 membered heterocyclic, and 4-7 membered heterocyclic optionally or independently substituted by one or more substituents selected from the group consisting of C1-6 alkyl, halogen, OH, and oxo;
C2-5alkenyl;
—C(O)NHC1-6 alkyl;
—C(O)N(C1-6 alkyl)2;
—C(O)-4-7 membered heterocyclyl;
—NHC1-6 alkyl optionally or independently substituted by one or more substituents selected from the group consisting of OH; and halogen;
—N(C1-6 alkyl)2 optionally or independently substituted by one or more substituents selected from the group consisting of OH; and halogen; and
-A-(R1A)m,
A is selected from the group consisting of C3-6 cycloalkyl; C6-10 aryl; 4-8 membered heterocyclyl; and 5-10 membered heteroaryl,
R1A is independently selected from the group consisting of
H;
OH;
NH2;
halogen;
C1-6alkyl optionally substituted by one or more substituents selected from the group consisting of OH, halogen, C3-6 cycloalkyl, —NHC1-6 alkyl, —NHC3-6 cycloalkyl, —N(C1-6 alkyl)2, —C(O)N(C1-6 alkyl)2, —NHC(O)C1-6 alkyl, 4-7 membered heterocyclyl optionally substituted by one or more substituents selected from the group consisting of halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, and —C(O)C1-6 alkyl;
C3-6 cycloalkyl optionally substituted by one or more substituents selected from the group consisting of OH, halogen and —N(C1-6 alkyl)2;
—C(O)C1-6 alkyl optionally substituted by one or more substituents selected from the group consisting of OH and halogen;
—C(O)N(C1-6 alkyl)2;
—C(O)-4-7 membered heterocyclyl optionally substituted by one or more substituents selected from the group consisting of OH and halogen;
—NHC1-6 alkyl optionally substituted by 4-7 membered heterocyclyl;
—N(C1-6 alkyl)2;
—S(O)2C1-6 alkyl;
—S(O)2C3-6 cycloalkyl;
oxo; and
4-11 membered heterocyclyl optionally or independently substituted by one or more substituents selected from the group consisting of halogen, C1-6alkyl optionally substituted by —N(C1-6 alkyl)2, C3-6 cycloalkyl, C1-6 haloalkyl, —C(O)C1-6 alkyl, and 4-7 membered heterocyclyl,
m is an integer of 0-2,
R2 is selected from the group consisting of —N(C1-6 alkyl)2 optionally substituted by one or more OHs; —XC1-6 alkyl optionally substituted by OH, halogen, C3-6 cycloalkyl, C1-3 alkoxy, —NHC1-6 alkyl, or —N(C1-6 alkyl)2; and —X(CH2)n—B—(R2A)o,
X is bond, —NH— or —O—,
n is an integer of 0-1,
o is an integer of 0-3,
B is selected from the group consisting of C3-7 cycloalkyl; C6-10 aryl; 4-12 membered heterocyclyl; and 5-6 membered heteroaryl,
R2A is each independently selected from the group consisting of H;
OH;
halogen;
C1-6 alkyl optionally or independently substituted by one or more substituents selected from the group consisting of OH, halogen, —NHC1-6 alkyl, —NHC1-6 haloalkyl, —N(C1-6 alkyl)2, 4-7 membered heterocyclyl, and C1-3 alkoxy;
C3-6cycloalkyl optionally or independently substituted by one or more substituents selected from the group consisting of OH, and halogen;
C1-3alkoxy optionally or independently substituted by one or more halogens;
—C(O)NHC1-6 alkyl;
—C(O)N(C1-6 alkyl)2; —C(O)NHC3-6 cycloalkyl;
—NHC1-6alkyl optionally or independently substituted by one or more substituents selected from the group consisting of OH, halogen, C3-6cycloalkyl, C1-3alkoxy, —NHC1-6 alkyl, —N(C1-6 alkyl)2, and 4-7 membered heterocyclyl;
—NHC3-6 cycloalkyl optionally or independently substituted by one or more substituents selected from the group consisting of OH and halogen;
—N(C1-6 alkyl)2 optionally or independently substituted by one or more substituents selected from the group consisting of OH and halogen;
—NHC(O)C1-6 alkyl;
—NHC(O)C3-6 cycloalkyl;
—NHS(O)2C1-6 alkyl;
—S(O)2C1-6 alkyl;
4-7 membered heterocyclyl optionally or independently substituted by one or more substituents selected from the group consisting of halogen and C1-6 alkyl;
═O; and
C(O)C1-6 alkyl,
R3 is Y-Q-(R3A)p,
Y is —NH— or bond,
p is an integer of 0 to 2,
Q is selected from the group consisting of 4-7 membered heterocyclyl; C6-10 aryl; and 5-6 membered heteroaryl,
R3A is independently selected from the group consisting of H; halogen; C1-6 alkyl optionally substituted by one or more substituents selected from the group consisting of halogen and C3-6 cycloalkyl; C3-6 cycloalkyl; 4-7 membered heterocyclyl; —S(O)2C1-6 alkyl optionally substituted by one to three halogens; —S(O)2C3-6 cycloalkyl optionally substituted by one or more halogens; and —S(O)2N(C1-6 alkyl), and
R4 is selected from the group consisting of H, halogen and C1-6 alkyl.