US 12,421,207 B2
Pyrimidinedione-based compounds as AXL, c-MET, and Mer inhibitors and methods of use thereof
Jin Sung Kim, Seoul (KR); Young Sang Kim, Goyang (KR); Sungmoo Kim, Seongnam (KR); Ju Hui Jeong, Seongnam (KR); Hyun Sook An, Seongnam (KR); and Soojeong Kim, Yongin (KR)
Assigned to CMG Pharmaceutical Co., Ltd., Seongnam (KR)
Filed by CMG Pharmaceutical Co., Ltd., Seongnam (KR)
Filed on Jan. 30, 2023, as Appl. No. 18/161,678.
Claims priority of provisional application 63/310,840, filed on Feb. 16, 2022.
Prior Publication US 2023/0348423 A1, Nov. 2, 2023
Int. Cl. C07D 401/12 (2006.01); A61K 31/513 (2006.01); A61K 31/53 (2006.01); A61K 31/5377 (2006.01); A61P 11/06 (2006.01); A61P 35/00 (2006.01); C07D 401/14 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01)
CPC C07D 401/12 (2013.01) [A61K 31/513 (2013.01); A61K 31/53 (2013.01); A61K 31/5377 (2013.01); A61P 11/06 (2018.01); A61P 35/00 (2018.01); C07D 401/14 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01)] 20 Claims
 
1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein
R1 is H, alkyl, haloalkyl, halo, or CN;
R2 is H, alkyl, haloalkyl, halo, or CN;
R3 is H or halo;
Q is unsubstituted alkyl, alkenyl, alkynyl, unsubstituted or substituted, cycloalkyl, unsubstituted or substituted, heterocyclyl, unsubstituted or substituted, heteroaryl, or unsubstituted or substituted, aryl, wherein said alkenyl or alkynyl is selected from the group consisting of:
—CH═CR4(CX′)m(CH2)nNR5R6, —C≡C(CX′)m(CH2)nNR5R6,
—CH═CR4(CX′)m(CH2)nCHR5R6, —C≡C(CX′)m(CH2)nCHR5R6,
—CH═CR4(CX′)m(CH2)nNR7OR8, and —C≡C(CX′)m(CH2)nNR7OR8;
wherein
R4 is hydrogen or halo;
X′ is H2, (C1-6 alkyl)2, or ═O;
m is 0 or 1;
n is 0 or 1-3;
—NR5R6 either forms a 4-7 membered heterocyclic ring or does not form a ring structure, the heterocyclic ring being either heteroaryl or heterocyclyl ring,
when —NR5R6 forms a 4-7 membered heterocyclic ring, the 4-7 membered heterocyclic ring includes an optional second heteroatom in addition to the nitrogen of —NR5R6 and is optionally substituted with one or more substituent groups independently selected from the group consisting of linear C1-C6 alkyl, branched C3-C6 alkyl, hydroxy, C1-C6 alkoxyalkyl, carboxylic acid, linear C1-C4 alkyl carboxylic acid, and branched C3-C4 alkyl carboxylic acid;
when —NR5R6 does not form a ring structure, R5 is selected from the group consisting of hydrogen, linear C1-C6 alkyl, and branched C3-C6 alkyl, and R6 is selected from the group consisting of hydrogen, linear C1-C6 alkyl optionally substituted with at least one fluoro or at least one hydroxy, branched C3-C6 alkyl optionally substituted with at least one fluoro or at least one hydroxy, and cycloalkyl optionally substituted with at least one fluoro or at least one hydroxy;
—CHR5R6 either forms a 4-7 membered heterocyclic ring or does not form a ring structure, the heterocyclic ring being either heteroaryl or heterocyclyl ring,
when —CHR5R6 forms a 4-7 membered heterocyclic ring, the 4-7 membered heterocyclic ring includes one or two heteroatoms and is optionally substituted with one or more substituent groups independently selected from the group consisting of linear C1-C6 alkyl, branched C3-C6 alkyl, hydroxy, C1-C6 alkoxyalkyl, carboxylic acid, linear C1-C4 alkyl carboxylic acid, and branched C3-C4 alkyl carboxylic acid;
when —CHR5R6 does not form a ring structure, R5 is selected from the group consisting of hydrogen, linear C1-C6 alkyl, and branched C3-C6 alkyl, and R6 is selected from the group consisting of hydrogen, linear C1-C6 alkyl optionally substituted with at least one fluoro or at least one hydroxy, branched C3-C6 alkyl optionally substituted with at least one fluoro or at least one hydroxy, and cycloalkyl optionally substituted with at least one fluoro or at least one hydroxy;
—NR7OR8 does not form a ring structure, R7 is selected from the group consisting of hydrogen, linear C1-C6 alkyl, and branched C3-C6 alkyl, and R1 is selected from the group consisting of hydrogen, linear C1-C6 alkyl optionally substituted with at least one fluoro, hydroxy, or alkoxy group, branched C3-C6 alkyl optionally substituted with at least one fluoro, hydroxy, or alkoxy group, and cycloalkyl optionally substituted with at least one fluoro, hydroxy, or alkoxy group;
G is

OG Complex Work Unit Chemistry
wherein
R9 is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl or heteroarylalkyl, where the heteroaryl group of heteroarylalkyl may be substituted or unsubstituted;
R10 is H, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl, alkyl or cycloalkyl, cycloalkylalkyl, alkenyl or alkynyl, where alkyl, alkenyl or cycloalkyl may be substituted by one, two or three groups selected from the group consisting of alkanoyl, cycloalkyl, alkenyl, alkynyl, halo, hydroxyl, alkoxy, alkoxycarbonyl, heterocyclyl, aryl, substituted aryl, aryloxy, arylalkoxy, amino, alkylamino, dialkylamino, where the alkyl groups of dialkylamino may be the same or different, heteroaryl, substituted heteroaryl, carboxyl, oxo, carbamoyl, alkylcarbamoyl, dialkycarbamoyl, where the alkyl groups of dialkylcarbamoyl may be the same or different and heterocyclylcarbonyl; and
Y is N, C—H, or C-alkyl.