IMIDAZOPYRIDIN COMPOUNDS, PHARMACEUTICALS AND HEALTH-BENEFICIAL FUNCTIONAL FOOD COMPOUNDS CONTAINING THEM

Abstract

The invention relates to: imidazopyridine compounds or their pharmaceutical salts; pharmaceutical compositions containing them as active ingredients for the prevention, improvement, or treatment of gastroenteritis or acid-related diseases; and health-enhancing food components containing them for the prevention or improvement of gastroenteritis or acid-related diseases.

Description

Novel imidazopyridine compound and composition containing the same as an active ingredient for preventing, improving or treating gastrointestinal inflammatory disease or gastric acid-related disease

[0001] The present invention relates to a novel imidazopyridine compound and a composition containing the same as an active ingredient for preventing, improving or treating gastrointestinal inflammatory diseases or gastric acid-related diseases.

[0002] peptic ulcer, stomach . Duodenal ulcer, gastritis, stomach . Gastrointestinal inflammatory diseases and acid-related diseases, such as gastroesophageal reflux disease (GERD) and non-erosive reflux disease (NERD), are the most common digestive diseases that affect most people in Korea and around the world.

[0003] Proton pump inhibitors (PPIs) are widely used to suppress gastric acid secretion. However, existing PPIs have problems in terms of effectiveness and side effects. Specifically, PPIs are activated by acid secretion into the form of sulfenamide, which is then released into the gastric mucosa. + / K +It has been pointed out that PPIs can cause side effects such as bacterial growth in the stomach, stimulation of proton pump expression, and the possibility of tumor cell formation due to hypergastrinemia by irreversibly binding to the cysteine ​​residue of ATPase and inhibiting gastric acid secretion for a long time. In addition, existing PPIs are unstable under acidic conditions, so they are often formulated as enteric-coated drugs. In such cases, it takes several hours for the onset of action, and it takes about 5 days for continuous administration to achieve maximum efficacy. In addition, PPIs are prodrugs that are activated by gastric acid and act only on the active proton pump, so there are disadvantages such as a delayed onset of maximum effect, a low effect in suppressing nocturnal acid secretion, and the need to take them before meals. In addition, PPIs are mainly metabolized through the CYP2C19 enzyme, and there is a large difference in efficacy between individuals due to genetic polymorphism of the CYP2C19 enzyme. Recently, it has been confirmed that long-term use increases the risk of hip, wrist, and spinal fractures by inhibiting calcium absorption and bone cell growth through stomach acid suppression.

[0004] Potassium-competitive acid blockers (P-CABs) are attracting attention to improve the shortcomings of the above-mentioned PPIs. Potassium-competitive acid blockers block the proton pump (H), an enzyme involved in the final stage of gastric acid secretion in gastric parietal cells. + / K + K in ATPase +They reversibly and competitively bind to ions and strongly and rapidly inhibit gastric acid secretion. These P-CAB agents show stronger inhibition than PPI agents at the normal acidity of the stomach (pH 1-3). However, the pharmacological activity that the inhibition effect decreases as the pH increases is required for gastric P-CAB agents, but some P-CAB agents show pharmacological activity that is maintained even when the pH increases, and some side effects related to this have been reported. In addition, since P-CAB agents are mainly metabolized through the CYP3A4 enzyme, the difference in pharmacological efficacy between individuals is relatively small, and concerns about interactions with drugs metabolized by the CYP2C19 enzyme are relatively low. In addition, they are easy to take regardless of whether they are before or after meals, and are expected to be very effective in improving nocturnal symptoms, which is a problem with PPIs.

[0005] The present invention is also related to a reversible proton pump inhibitor (P-CAB), and examples of representative reversible proton pump inhibitors known in the art include Fexuprazan, Tegoprazan, and Linaprazan.

[0006] The present invention provides an imidazopyridine compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof as a reversible proton pump inhibitor useful for preventing, improving or treating gastrointestinal inflammatory diseases and gastric acid-related diseases:

[0007] [Chemical Formula 1]

[0008]

[0009] In the above chemical formula 1,

[0010] R1 is , , , , or And,

[0011] At this time, R1a Inland R 1k is independently hydrogen, a cyano group, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C1 to C30 heteroalkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C2 to C30 alkynyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group, or R 1a Inland R 1k Among them, adjacent groups are connected to each other to form a substituted or unsubstituted aliphatic ring structure or a substituted or unsubstituted aromatic ring structure;

[0012] R2 is -NR 2a R 2b And, at this time, R 2a R 2b is independently hydrogen, a cyano group, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C2 to C30 alkynyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group;

[0013] R3 or R4 is independently hydrogen, a cyano group, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C2 to C30 alkynyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group.

[0014] However, the technical problems to be solved by the present invention are not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the description below.

[0015] The present invention provides an imidazopyridine compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof:

[0016] [Chemical Formula 1]

[0017]

[0018] In the above chemical formula 1,

[0019] R1 is , , , , or And,

[0020] At this time, R 1a Inland R 1kis independently hydrogen, a cyano group, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C1 to C30 heteroalkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C2 to C30 alkynyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group, or R 1a Inland R 1k Among them, adjacent groups are connected to each other to form a substituted or unsubstituted aliphatic ring structure or a substituted or unsubstituted aromatic ring structure;

[0021] R2 is -NR 2a R 2b And, at this time, R 2a R 2b is independently hydrogen, a cyano group, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C2 to C30 alkynyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group;

[0022] R3 or R4 is independently hydrogen, a cyano group, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C2 to C30 alkynyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group.

[0023] The above R1 is , , or And,

[0024] At this time, R 1c Inland R 1i is independently hydrogen, a substituted or unsubstituted C1 to C12 alkyl group, a substituted or unsubstituted C1 to C12 heteroalkyl group, a substituted or unsubstituted C3 to C12 cycloalkyl group, a substituted or unsubstituted C6 to C12 aryl group, a substituted or unsubstituted C7 to C12 arylalkyl group, a substituted or unsubstituted C2 to C12 heteroaryl group, or a substituted or unsubstituted C3 to C12 heteroarylalkyl group, or R 1c Inland R 1i Among them, adjacent groups can be connected to each other to form a substituted or unsubstituted 12-membered or less aliphatic ring structure or a substituted or unsubstituted 12-membered or less aromatic ring structure.

[0025] The above R2 is -NR 2a R 2b And, at this time, R 2a is hydrogen, and R 2b may be a substituted or unsubstituted C7 to C12 arylalkyl group.

[0026] The above R3 or R4 can independently be hydrogen, or a substituted or unsubstituted C1 to C12 alkyl group.

[0027] The above compound or a pharmaceutically acceptable salt thereof

[0028] (1) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclopentanecarboxamide;

[0029] (2) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclopropanecarboxamide;

[0030] (3) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclohexanecarboxamide;

[0031] (4) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0032] (5) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclobutanecarboxamide;

[0033] (6) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-1-carboxamide;

[0034] (7) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)isobutyramide;

[0035] (8) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)pivalamide;

[0036] (9) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2,2-difluoroacetamide;

[0037] (10) 2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0038] (11) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)pyrrolidine-1-carboxamide;

[0039] (12) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)bicyclo[1.1.1]pentane-1-carboxamide;

[0040] (13) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)propionamide;

[0041] (14) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)oxazole-2-carboxamide;

[0042] (15) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methoxyacetamide;

[0043] (16) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2,2-difluoropropanamide;

[0044] (17) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-fluorocyclobutane-1-carboxamide;

[0045] (18) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclobutanesulfonamide;

[0046] (19) (S)-2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)propanamide;

[0047] (20) (R)-2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)propanamide;

[0048] (21) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0049] (22) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-ethylurea;

[0050] (23) 1-Cyclobutyl-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea;

[0051] (24) 1-Cyclopropyl-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea;

[0052] (25) 2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl acetate;

[0053] (26) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-hydroxyacetamide;

[0054] (27) 2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methylpropanamide;

[0055] (28) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidin-2-one;

[0056] (29) 1-(bicyclo[1.1.1]pentan-1-yl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea;

[0057] (30) 1-(cyclopropylmethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea;

[0058] (31) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-isopropylurea;

[0059] (32) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-ethyl-1-methylurea;

[0060] (33) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-ethyl-1-methylurea;

[0061] (34) 3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-3-oxopropanoate;

[0062] (35) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide;

[0063] (36) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide;

[0064] (37) 1-(2-aminoethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea;

[0065] (38) 4-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-4-oxobutanoic acid;

[0066] (39) 3-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl)propanoic acid;

[0067] (40) Ethyl 4-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-4-oxobutanoate;

[0068] (41) tert-Butyl 3-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl)propanoate;

[0069] (42) tert-butyl (2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)ethyl)carbamate;

[0070] (43) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,1-dimethylurea;

[0071] (44) 1-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-methylurea;

[0072] (45) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0073] (46) Methyl((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)carbamoyl)glycinate;

[0074] (47) 2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)-N-methylacetamide;

[0075] (48) 2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)-N,N-dimethylacetamide;

[0076] (49) 3-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,1-dimethylurea;

[0077] (50) 1-Cyclopropyl-3-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)urea;

[0078] (51) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)azetidine-1-carboxamide;

[0079] (52) 2-Acetamido-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0080] (53) 2-(dimethylamino)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0081] (54) 1-Butyl-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea;

[0082] (55) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)pivalamide;

[0083] (56) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-2,2-difluoroacetamide;

[0084] (57) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-2,2-difluoropropanamide;

[0085] (58) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-3-hydroxycyclobutane-1-carboxamide;

[0086] (59) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-3-fluorocyclobutane-1-carboxamide;

[0087] (60) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)imidazolidine-2,4-dione;

[0088] (61) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)morpholine-4-carboxamide;

[0089] (62) 2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)ureido)ethyl acetate;

[0090] (63) (S)-2-amino-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)propanamide;

[0091] (64) 2-amino-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)acetamide;

[0092] (65) (S)-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide;

[0093] (66) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-2-azaspiro[3.3]heptane-2-carboxamide;

[0094] (67) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-2-azaspiro[3.3]heptane-2-carboxamide;

[0095] (68) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;

[0096] (69) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-3-oxoazetidine-1-carboxamide;

[0097] (70) ((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)carbamoyl)glycine;

[0098] (71) 3-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)propionic acid;

[0099] (72) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,3,5-triazepane-2,4-dione;

[0100] (73) N-(2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)ethyl)acetamide;

[0101] (74) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-3-((tetrohydrofuran-3-yl)methyl)urea;

[0102] (75) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methylazetidine-2-carboxamide;

[0103] (76) (R)-2-(azetidin-2-yl)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)acetamide;

[0104] (77) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-phenylazetidine-1-carboxamide;

[0105] (78) (S)-1-(2,3-dihydro-1H-inden-1-yl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)urea;

[0106] (79) (S)-N2-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-N1-methylazetidine-1,2-dicarboxamide;

[0107] (80) (R)-1-(2,3-dihydro-1H-inden-1-yl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)urea;

[0108] (81) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(2-oxoazetidin-1-yl)acetamide;

[0109] (82) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-4-phenylpiperidine-1-carboxamide;

[0110] (83) N-(8-((2,6-dimethylbenzyl l)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-phenylpiperidine-1-carboxamide;

[0111] (84) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-phenylpyrrolidine-1-carboxamide;

[0112] (85) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-2-carboxamide;

[0113] (86) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxyacetamide;

[0114] (87) 1-(2-aminoethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-methylurea;

[0115] (88) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-(2-hydroxyethyl)urea;

[0116] (89) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)pyrrolidine-3-carboxamide;

[0117] (90) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-2-carboxamide;

[0118] (91) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(pyrrolidin-2-yl)acetamide;

[0119] (92) N 8 -(2,6-Dimethylbenzyl)-N6-isopropyl-2,3-dimethylimadzo[1,2-a]pyridine-6,8-diamine;

[0120] (93) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(pyrrolidin-2-yl)acetamide;

[0121] (94) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-2-carboxamide;

[0122] (95) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(2-hydroxyacetamido)acetamide;

[0123] (96) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide;

[0124] (97) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide;

[0125] (98) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(methylamino)acetamide;

[0126] (99) 3-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)propanamide;

[0127] (100) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-methoxyacetamide;

[0128] (101) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-hydroxypropanamide;

[0129] (102) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-hydroxypropanamide;

[0130] (103) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-1-carboxamide;

[0131] (104) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)benzamide;

[0132] (105) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)pyrrolidine-3-carboxamide;

[0133] (106) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-2-carboxamide;

[0134] (107) (E)-4-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)amino)-3-oxoprop-1-en-1-yl)phenyl acetate;

[0135] (108) (E)-4-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)amino)-3-oxoprop-1-en-1-yl)-2-methoxyphenyl acetate;

[0136] (109) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)aziridine-2-carboxamide;

[0137] (110) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-1-(2-hydroxyacetyl)pyrrolidine-3-carboxamide;

[0138] (111) (R)-1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl acetate;

[0139] (112) (S)-1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl acetate;

[0140] (113) 1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)cyclopropyl acetate;

[0141] (114) (S)-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide;

[0142] (115) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-1-hydroxycyclopropane-1-carboxamide;

[0143] (116) 3-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazolidine[1,2-a]pyridin-6-yl)-1-methylimidazolidine-2,4-dione;

[0144] (117) (R)-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide;

[0145] (118) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-3-carboxamide;

[0146] (119) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-3-(2-hydroxyacetamido)propanamide;

[0147] (120) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-1-(2-hydroxyacetyl)piperidine-3-carboxamide;

[0148] (121) N 8 -(2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine; and

[0149] (122) N 8 -(4-fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine.

[0150] The compound or a pharmaceutically acceptable salt thereof may have an inhibitory ability against proton pump activity.

[0151] As one embodiment of the present invention, a pharmaceutical composition for preventing or treating gastrointestinal inflammatory disease or gastric acid-related disease is provided, comprising the imidazopyridine compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0152] The above compound or a pharmaceutically acceptable salt thereof can act as a reversible proton pump inhibitor.

[0153] The above compound or a pharmaceutically acceptable salt thereof can suppress gastric acid secretion.

[0154] The above gastrointestinal inflammatory disease or gastric acid-related disease may be at least one selected from the group consisting of peptic ulcer, gastric / duodenal ulcer, nonsteroidal anti-inflammatory drug (NSAID)-induced ulcer, Helicobacter pylori infection, functional dyspepsia, Zollinger-Ellison syndrome, gastritis, and gastroesophageal reflux disease (GERD) and non-erosive reflux disease (NERD).

[0155] In another embodiment of the present invention, a health functional food composition for preventing or improving gastrointestinal inflammatory disease or gastric acid-related disease is provided, comprising the imidazopyridine compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0156] The novel imidazopyridine compound or pharmaceutically acceptable salt thereof according to the present invention can act as a reversible proton pump inhibitor due to its proton pump inhibitory activity. Furthermore, it has the advantage of being useful for the prevention, improvement, or treatment of gastrointestinal inflammatory diseases or gastric acid-related diseases by effectively suppressing gastric acid secretion.

[0157] The present inventors have developed a method for treating peptic ulcer, gastric . Duodenal ulcer, gastritis, stomach . As a result of efforts to develop reversible proton pump inhibitors that can be useful for preventing, improving, or treating gastrointestinal inflammatory diseases and gastric acid-related diseases such as gastroesophageal reflux disease (GERD) and non-erosive reflux disease (NERD), the inventors synthesized novel imidazopyridine compounds and confirmed that they have proton pump inhibitory activity in in vitro experiments and effectively inhibit gastric acid secretion in in vivo experiments, thereby completing the present invention.

[0158]

[0159] Hereinafter, the present invention will be described in detail.

[0160]

[0161] Novel imidazopyridine compound or pharmaceutically acceptable salt thereof

[0162]

[0163] The present invention provides an imidazopyridine compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof:

[0164] [Chemical Formula 1]

[0165]

[0166] In the above chemical formula 1,

[0167] R1 is , , , , or And,

[0168] At this time, R 1a Inland R 1k is independently hydrogen, a cyano group, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C1 to C30 heteroalkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C2 to C30 alkynyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group, or R 1a Inland R 1k Among them, adjacent groups are connected to each other to form a substituted or unsubstituted aliphatic ring structure or a substituted or unsubstituted aromatic ring structure;

[0169] R2 is -NR 2a R 2b And, at this time, R 2a R 2bis independently hydrogen, a cyano group, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C2 to C30 alkynyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group;

[0170] R3 or R4 is independently hydrogen, a cyano group, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C2 to C30 alkynyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group.

[0171]

[0172] The term "heteroalkyl" as used herein means an alkyl group containing a heteroatom. Here, C represents the number of carbon atoms not substituted with a heteroatom.

[0173] In addition, "cycloalkyl" in this specification means an aliphatic ring structure composed of carbon, and "aryl" means an aromatic ring structure composed of carbon. Meanwhile, "heteroaryl" in this specification is a concept that includes both an aliphatic ring structure containing a heteroatom and a substituted or unsubstituted aromatic ring structure. Here, C means the number of carbons not substituted with a heteroatom.

[0174] As used herein, “substitution” means substitution by a halogen group; a hydroxyl group; a C1 to C30 (especially C1 to C12) alkoxy group; an amine group; a C1 to C30 (especially C1 to C12) alkylamine group; a carboxyl group; a further substituted or unsubstituted C6 to C30 (especially C6 to C12) aryl group; a further substituted or unsubstituted C1 to C30 (especially C1 to C12) alkyl group linked via an ester, amide, ether or carbonyl bond; or a further substituted or unsubstituted C3 to C30 (especially C3 to C12) cycloalkyl group linked via an ester, amide, ether or carbonyl bond.

[0175] In addition, "additional substitution" in the present specification means substitution by a halogen group; a hydroxy group; an alkoxy group of C1 to C30 (especially C1 to C12); an amine group; an alkylamine group of C1 to C30 (especially C1 to C12); a carboxyl group; an aryl group of C6 to C30 (especially C6 to C12); an alkyl group of C1 to C30 (especially C1 to C12) linked via an ester, amide, ether or carbonyl bond; or a cycloalkyl group of C3 to C30 (especially C3 to C12) linked via an ester, amide, ether or carbonyl bond.

[0176]

[0177] Specifically, in the above chemical formula 1, R1 is If , R 1a or R 1b can independently be hydrogen, or a substituted or unsubstituted C1 to C30 alkyl group, and R 1a or R 1b is independently hydrogen, or a substituted or unsubstituted C1 to C12 alkyl group, but is not limited thereto. For example, R 1a or R 1b can independently be hydrogen or isopropyl group.

[0178]

[0179] In addition, in the above chemical formula 1, R1 If so, first, R 1c may be hydrogen, or a substituted or unsubstituted C1 to C30 alkyl group, and R 1c is preferably hydrogen, or a substituted or unsubstituted C1 to C12 alkyl group, but is not limited thereto. For example, R 1c can be hydrogen. On the other hand, R 1d may be hydrogen, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C1 to C30 heteroalkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group. Preferably, R 1d may be hydrogen, a substituted or unsubstituted C1 to C12 alkyl group, a substituted or unsubstituted C1 to C12 heteroalkyl group, a substituted or unsubstituted C3 to C12 cycloalkyl group, a substituted or unsubstituted C6 to C12 aryl group, a substituted or unsubstituted C7 to C12 arylalkyl group, a substituted or unsubstituted C2 to C12 heteroaryl group, or a substituted or unsubstituted C3 to C12 heteroarylalkyl group. For example, R 1dis a cyclopentyl group, a cyclopropyl group, a cyclohexyl group, a methyl group, a cyclobutyl group, an isopropyl group, a tert-butyl group, a difluoromethyl group, an aminomethyl group, a bicyclo[1.1.1]pentan-1-yl group, an ethyl group, an oxazol-2-yl group, a methoxymethyl group, a 1,1-difluoroethyl group, a 3-fluorocyclobutyl group, a 1-aminoethyl group, a methoxy group, a 1-aminoisopropyl group, a dimethylaminomethyl group, a 1-aminoethyl group, a 1-ethanol group, a methylaminomethyl group, a 2-aminoethyl group, a 2-ethanol group, a phenyl group, a cyclopropanol group, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or It can be. In particular, R 1c is hydrogen, and R 1d is a methyl group, aminomethyl group, methoxymethyl group, methoxy group, , , , 2-ethanol group, cyclopropanol group, or 1-ethanol group are preferable in terms of inhibition of proton pump activity.

[0180] Or, R 1c and R 1dcan be linked to each other to form a substituted or unsubstituted aliphatic ring structure or a substituted or unsubstituted aromatic ring structure, and R 1c and R 1d It is preferable that they are connected to each other to form a substituted or unsubstituted 12-membered or less aliphatic ring structure or a substituted or unsubstituted 12-membered or less aromatic ring structure, but it is not limited thereto. For example, R1 itself is It could be.

[0181]

[0182] In addition, in the above chemical formula 1, R1 If , R 1e and R 1f can be linked to each other to form a substituted or unsubstituted aliphatic ring structure or a substituted or unsubstituted aromatic ring structure, and R 1e and R 1f It is preferable that they are connected to each other to form a substituted or unsubstituted 12-membered or less aliphatic ring structure or a substituted or unsubstituted 12-membered or less aromatic ring structure, but it is not limited thereto. For example, R1 itself is , , or It could be. In particular, R1 itself This is desirable in terms of inhibition of proton pump activity.

[0183]

[0184] In addition, in the above chemical formula 1, R1 If so, first, R 1g may be hydrogen, or a substituted or unsubstituted C1 to C30 alkyl group, and R 1g is preferably hydrogen, or a substituted or unsubstituted C1 to C12 alkyl group, but is not limited thereto. For example, R 1g can be hydrogen. On the other hand, R 1h or R 1imay independently be hydrogen, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C1 to C30 heteroalkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group. Preferably, R 1d may be hydrogen, a substituted or unsubstituted C1 to C12 alkyl group, a substituted or unsubstituted C1 to C12 heteroalkyl group, a substituted or unsubstituted C3 to C12 cycloalkyl group, a substituted or unsubstituted C6 to C12 aryl group, a substituted or unsubstituted C7 to C12 arylalkyl group, a substituted or unsubstituted C2 to C12 heteroaryl group, or a substituted or unsubstituted C3 to C12 heteroarylalkyl group. For example, R 1h or R 1i is independently hydrogen, ethyl group, cyclobutyl group, cyclopropyl group, bicyclo[1.1.1]pentan-1-yl group, cyclopropylmethyl group, isopropyl group, 2-aminoethyl group, cyano group, methyl group, 2-ethanol group, , , , , , , or It can be. In particular, R 1g is hydrogen, and R 1h is hydrogen or methyl group, and R 1i It is preferable that the group be a cyclopropyl group, a methyl group, a 2-aminoethyl group, or a 2-ethanol group in terms of inhibition of proton pump activity.

[0185] Or, R 1h and R 1iare linked to each other to form a substituted or unsubstituted aliphatic ring structure or a substituted or unsubstituted aromatic ring structure, and R 1h and R 1i It is preferable that they are connected to each other to form a substituted or unsubstituted 12-membered or less aliphatic ring structure or a substituted or unsubstituted 12-membered or less aromatic ring structure, but it is not limited thereto. For example, R1 itself is , , , , , , , , , , , or It could be. In particular, R1 itself , or This is desirable in terms of inhibition of proton pump activity.

[0186]

[0187] Also, R1 If so, first, R 1j may be hydrogen, or a substituted or unsubstituted C1 to C30 alkyl group, and R 1j is preferably hydrogen, or a substituted or unsubstituted C1 to C12 alkyl group, but is not limited thereto. For example, R 1j can be hydrogen. On the other hand, R 1kmay be hydrogen, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C1 to C30 heteroalkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group. Preferably, R 1d may be hydrogen, a substituted or unsubstituted C1 to C12 alkyl group, a substituted or unsubstituted C1 to C12 heteroalkyl group, a substituted or unsubstituted C3 to C12 cycloalkyl group, a substituted or unsubstituted C6 to C12 aryl group, a substituted or unsubstituted C7 to C12 arylalkyl group, a substituted or unsubstituted C2 to C12 heteroaryl group, or a substituted or unsubstituted C3 to C12 heteroarylalkyl group. For example, R 1k may be a cyclobutyl group.

[0188]

[0189] Specifically, in the above chemical formula 1, R2 is -NR 2a R 2b If, then, R 2a can be hydrogen. On the other hand, R 2b may be a substituted or unsubstituted C7 to C30 arylalkyl group, and is preferably a substituted or unsubstituted C7 to C12 arylalkyl group, but is not limited thereto. For example, R 2b may be a 2,6-dimethyl benzyl group or a 4-fluoro-2,6-dimethyl benzyl group.

[0190]

[0191] Specifically, in the above chemical formula 1, R3 or R4 can independently be hydrogen, or a substituted or unsubstituted C1 to C30 alkyl group, and it is preferable that R3 or R4 independently be hydrogen, or a substituted or unsubstituted C1 to C12 alkyl group, but this is not limited thereto. For example, R3 or R4 can independently be a methyl group.

[0192]

[0193] More specifically, the compound or a pharmaceutically acceptable salt thereof

[0194] (1) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclopentanecarboxamide;

[0195] (2) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclopropanecarboxamide;

[0196] (3) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclohexanecarboxamide;

[0197] (4) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0198] (5) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclobutanecarboxamide;

[0199] (6) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-1-carboxamide;

[0200] (7) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)isobutyramide;

[0201] (8) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)pivalamide;

[0202] (9) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2,2-difluoroacetamide;

[0203] (10) 2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0204] (11) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)pyrrolidine-1-carboxamide;

[0205] (12) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)bicyclo[1.1.1]pentane-1-carboxamide;

[0206] (13) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)propionamide;

[0207] (14) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)oxazole-2-carboxamide;

[0208] (15) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methoxyacetamide;

[0209] (16) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2,2-difluoropropanamide;

[0210] (17) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-fluorocyclobutane-1-carboxamide;

[0211] (18) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclobutanesulfonamide;

[0212] (19) (S)-2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)propanamide;

[0213] (20) (R)-2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)propanamide;

[0214] (21) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0215] (22) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-ethylurea;

[0216] (23) 1-Cyclobutyl-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea;

[0217] (24) 1-Cyclopropyl-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea;

[0218] (25) 2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl acetate;

[0219] (26) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-hydroxyacetamide;

[0220] (27) 2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methylpropanamide;

[0221] (28) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidin-2-one;

[0222] (29) 1-(bicyclo[1.1.1]pentan-1-yl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea;

[0223] (30) 1-(cyclopropylmethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea;

[0224] (31) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-isopropylurea;

[0225] (32) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-ethyl-1-methylurea;

[0226] (33) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-ethyl-1-methylurea;

[0227] (34) 3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-3-oxopropanoate;

[0228] (35) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide;

[0229] (36) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide;

[0230] (37) 1-(2-aminoethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea;

[0231] (38) 4-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-4-oxobutanoic acid;

[0232] (39) 3-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl)propanoic acid;

[0233] (40) Ethyl 4-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-4-oxobutanoate;

[0234] (41) tert-Butyl 3-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl)propanoate;

[0235] (42) tert-butyl (2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)ethyl)carbamate;

[0236] (43) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,1-dimethylurea;

[0237] (44) 1-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-methylurea;

[0238] (45) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0239] (46) Methyl((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)carbamoyl)glycinate;

[0240] (47) 2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)-N-methylacetamide;

[0241] (48) 2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)-N,N-dimethylacetamide;

[0242] (49) 3-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,1-dimethylurea;

[0243] (50) 1-Cyclopropyl-3-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)urea;

[0244] (51) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)azetidine-1-carboxamide;

[0245] (52) 2-Acetamido-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0246] (53) 2-(dimethylamino)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0247] (54) 1-Butyl-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea;

[0248] (55) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)pivalamide;

[0249] (56) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-2,2-difluoroacetamide;

[0250] (57) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-2,2-difluoropropanamide;

[0251] (58) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-3-hydroxycyclobutane-1-carboxamide;

[0252] (59) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-3-fluorocyclobutane-1-carboxamide;

[0253] (60) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)imidazolidine-2,4-dione;

[0254] (61) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)morpholine-4-carboxamide;

[0255] (62) 2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)ureido)ethyl acetate;

[0256] (63) (S)-2-amino-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)propanamide;

[0257] (64) 2-amino-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)acetamide;

[0258] (65) (S)-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide;

[0259] (66) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-2-azaspiro[3.3]heptane-2-carboxamide;

[0260] (67) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-2-azaspiro[3.3]heptane-2-carboxamide;

[0261] (68) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;

[0262] (69) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-3-oxoazetidine-1-carboxamide;

[0263] (70) ((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)carbamoyl)glycine;

[0264] (71) 3-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)propionic acid;

[0265] (72) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,3,5-triazepane-2,4-dione;

[0266] (73) N-(2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)ethyl)acetamide;

[0267] (74) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-3-((tetrohydrofuran-3-yl)methyl)urea;

[0268] (75) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methylazetidine-2-carboxamide;

[0269] (76) (R)-2-(azetidin-2-yl)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)acetamide;

[0270] (77) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-phenylazetidine-1-carboxamide;

[0271] (78) (S)-1-(2,3-dihydro-1H-inden-1-yl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)urea;

[0272] (79) (S)-N2-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-N1-methylazetidine-1,2-dicarboxamide;

[0273] (80) (R)-1-(2,3-dihydro-1H-inden-1-yl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)urea;

[0274] (81) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(2-oxoazetidin-1-yl)acetamide;

[0275] (82) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-4-phenylpiperidine-1-carboxamide;

[0276] (83) N-(8-((2,6-dimethylbenzyl l)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-phenylpiperidine-1-carboxamide;

[0277] (84) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-phenylpyrrolidine-1-carboxamide;

[0278] (85) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-2-carboxamide;

[0279] (86) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxyacetamide;

[0280] (87) 1-(2-aminoethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-methylurea;

[0281] (88) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-(2-hydroxyethyl)urea;

[0282] (89) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)pyrrolidine-3-carboxamide;

[0283] (90) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-2-carboxamide;

[0284] (91) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(pyrrolidin-2-yl)acetamide;

[0285] (92) N 8 -(2,6-Dimethylbenzyl)-N6-isopropyl-2,3-dimethylimadzo[1,2-a]pyridine-6,8-diamine;

[0286] (93) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(pyrrolidin-2-yl)acetamide;

[0287] (94) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-2-carboxamide;

[0288] (95) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(2-hydroxyacetamido)acetamide;

[0289] (96) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide;

[0290] (97) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide;

[0291] (98) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(methylamino)acetamide;

[0292] (99) 3-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)propanamide;

[0293] (100) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-methoxyacetamide;

[0294] (101) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-hydroxypropanamide;

[0295] (102) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-hydroxypropanamide;

[0296] (103) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-1-carboxamide;

[0297] (104) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)benzamide;

[0298] (105) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)pyrrolidine-3-carboxamide;

[0299] (106) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-2-carboxamide;

[0300] (107) (E)-4-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)amino)-3-oxoprop-1-en-1-yl)phenyl acetate;

[0301] (108) (E)-4-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)amino)-3-oxoprop-1-en-1-yl)-2-methoxyphenyl acetate;

[0302] (109) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)aziridine-2-carboxamide;

[0303] (110) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-1-(2-hydroxyacetyl)pyrrolidine-3-carboxamide;

[0304] (111) (R)-1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl acetate;

[0305] (112) (S)-1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl acetate;

[0306] (113) 1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)cyclopropyl acetate;

[0307] (114) (S)-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide;

[0308] (115) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-1-hydroxycyclopropane-1-carboxamide;

[0309] (116) 3-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazolidine[1,2-a]pyridin-6-yl)-1-methylimidazolidine-2,4-dione;

[0310] (117) (R)-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide;

[0311] (118) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-3-carboxamide;

[0312] (119) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-3-(2-hydroxyacetamido)propanamide;

[0313] (120) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-1-(2-hydroxyacetyl)piperidine-3-carboxamide;

[0314] (121) N 8 -(2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine; and

[0315] (122) N 8 -(4-fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine.

[0316]

[0317] Preferably, the compound or a pharmaceutically acceptable salt thereof

[0318] (4) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0319] (10) 2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0320] (15) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methoxyacetamide;

[0321] (21) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0322] (24) 1-Cyclopropyl-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea;

[0323] (26) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-hydroxyacetamide;

[0324] (33) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-ethyl-1-methylurea;

[0325] (43) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,1-dimethylurea;

[0326] (44) 1-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-methylurea;

[0327] (45) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0328] (49) 3-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,1-dimethylurea;

[0329] (50) 1-Cyclopropyl-3-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)urea;

[0330] (51) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)azetidine-1-carboxamide;

[0331] (60) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)imidazolidine-2,4-dione;

[0332] (64) 2-amino-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)acetamide;

[0333] (77) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-phenylazetidine-1-carboxamide;

[0334] (86) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxyacetamide;

[0335] (87) 1-(2-aminoethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-methylurea;

[0336] (88) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-(2-hydroxyethyl)urea;

[0337] (93) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(pyrrolidin-2-yl)acetamide;

[0338] (94) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-2-carboxamide;

[0339] (95) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(2-hydroxyacetamido)acetamide;

[0340] (100) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-methoxyacetamide;

[0341] (101) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-hydroxypropanamide;

[0342] (102) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-hydroxypropanamide;

[0343] (115) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-1-hydroxycyclopropane-1-carboxamide; and

[0344] (117) It may be at least one selected from the group consisting of (R)-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide.

[0345]

[0346] More preferably, the compound or a pharmaceutically acceptable salt thereof

[0347] (4) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0348] (15) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methoxyacetamide;

[0349] (21) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0350] (26) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-hydroxyacetamide;

[0351] (45) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide;

[0352] (60) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)imidazolidine-2,4-dione;

[0353] (86) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxyacetamide;

[0354] (100) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-methoxyacetamide;

[0355] (101) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-hydroxypropanamide; and

[0356] (102) It may be at least one selected from the group consisting of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-hydroxypropanamide.

[0357]

[0358] The above compound or a pharmaceutically acceptable salt thereof may have an inhibitory ability against proton pump activity, and the proton pump (H + , K +-ATPase) activity. This can be confirmed by measuring the inhibitory ability. Therefore, it can act as a reversible proton pump inhibitor and has the advantage of being useful for the prevention, improvement, or treatment of gastrointestinal inflammatory diseases or gastric acid-related diseases by effectively suppressing gastric acid secretion.

[0359]

[0360] Pharmaceutical composition for preventing or treating gastrointestinal inflammatory diseases or gastric acid-related diseases

[0361]

[0362] The present invention provides a pharmaceutical composition for preventing or treating gastrointestinal inflammatory diseases or gastric acid-related diseases, comprising the above-described imidazopyridine compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0363] Since the specific structure of the above compound or its pharmaceutically acceptable salt has been described above, a redundant description will be omitted.

[0364] The above compound or a pharmaceutically acceptable salt thereof can act as a reversible proton pump inhibitor. Such a reversible proton pump inhibitor improves the disadvantages of PPIs and acts by inhibiting the proton pump (H), an enzyme involved in the final stage of gastric acid secretion in gastric parietal cells. + / K + K in ATPase + It reversibly and competitively binds to ions, potently and rapidly inhibiting gastric acid secretion. Furthermore, because it is primarily metabolized by the CYP3A4 enzyme, interindividual differences in efficacy are relatively small, and concerns about interactions with drugs metabolized by the CYP2C19 enzyme are relatively low. Furthermore, it is easy to take, regardless of whether it is before or after meals, and is highly effective in alleviating nocturnal symptoms.

[0365] Additionally, the compound or a pharmaceutically acceptable salt thereof can suppress gastric acid secretion.

[0366] Accordingly, the compound or a pharmaceutically acceptable salt thereof can be used for the prevention or treatment of gastrointestinal inflammatory diseases or gastric acid-related diseases. The gastrointestinal inflammatory diseases or gastric acid-related diseases may be at least one selected from the group consisting of peptic ulcer, gastric / duodenal ulcer, nonsteroidal anti-inflammatory drug (NSAID)-induced ulcer, Helicobacter pylori infection, functional dyspepsia, Zollinger-Ellison syndrome, gastritis, gastroesophageal reflux disease (GERD), and non-erosive reflux disease (NERD).

[0367]

[0368] The pharmaceutical composition according to the present invention can be formulated and used in the form of oral preparations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injection solutions, according to conventional methods, and may include appropriate carriers, excipients, or diluents conventionally used in the manufacture of pharmaceutical compositions for formulation.

[0369] The carrier or excipient or diluent may include various compounds or mixtures including lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil.

[0370] When formulating, it can be manufactured using diluents or excipients such as fillers, weighting agents, binders, wetting agents, disintegrants, and surfactants that are commonly used.

[0371] Solid preparations for oral administration can be prepared by mixing the imidazopyridine compound or a pharmaceutically acceptable salt thereof with at least one excipient, such as starch, calcium carbonate, sucrose or lactose, or gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc can also be used.

[0372] Liquid preparations for oral administration include suspensions, solutions, emulsions, and syrups, and in addition to commonly used simple diluents such as water and liquid paraffin, they may contain various excipients such as wetting agents, sweeteners, fragrances, and preservatives.

[0373] Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solutions and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases include witepsol, macrogol, Tween 61, cocoa butter, laurin, and glycerol gelatin.

[0374] The preferred dosage of the pharmaceutical composition according to the present invention varies depending on the patient's condition, body weight, severity of the disease, drug form, route of administration, and duration of administration, but can be appropriately selected by those skilled in the art. However, for desirable effects, the dosage may be 0.0001 to 2,000 mg / kg per day, preferably 0.001 to 2,000 mg / kg. Administration may be once a day or divided into several doses. However, the scope of the present invention is not limited by the above dosage.

[0375] The pharmaceutical composition according to the present invention can be administered to mammals such as rats, mice, livestock, and humans via various routes. All modes of administration can be administered, for example, orally, rectally, or by intravenous, intramuscular, subcutaneous, intrauterine, or intracerebroventricular injection.

[0376]

[0377] Health functional food composition for preventing or improving gastrointestinal inflammatory disease or gastric acid-related disease

[0378]

[0379] In another embodiment of the present invention, a health functional food composition for preventing or improving gastrointestinal inflammatory disease or gastric acid-related disease is provided, comprising the imidazopyridine compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0380] Since the specific structure and action of the above compound or its pharmaceutically acceptable salt have been described above, a redundant description will be omitted.

[0381] The above gastrointestinal inflammatory disease or gastric acid-related disease may be at least one selected from the group consisting of peptic ulcer, gastric / duodenal ulcer, nonsteroidal anti-inflammatory drug (NSAID)-induced ulcer, Helicobacter pylori infection, functional dyspepsia, Zollinger-Ellison syndrome, gastritis, and gastroesophageal reflux disease (GERD) and non-erosive reflux disease (NERD).

[0382]

[0383] In the food or health functional food composition according to the present invention, when the imidazopyridine compound or its pharmaceutically acceptable salt is used as an additive to a health functional food, it may be added as is or used together with other foods or food ingredients, and may be used appropriately according to conventional methods. The amount of active ingredients mixed may be appropriately determined depending on the intended use, such as prevention, health, or treatment.

[0384] The formulation of health functional foods can be in the form of powders, granules, pills, tablets, capsules, or any other form of general food or beverage.

[0385] There is no particular limitation on the types of the above foods, and examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes, and all foods in the conventional sense can be included.

[0386] In general, when manufacturing food or beverages, the imidazopyridine compound or its pharmaceutically acceptable salt may be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, per 100 parts by weight of the raw material. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range.

[0387] Among the health functional foods according to the present invention, the beverage may contain various flavoring agents or natural carbohydrates as additional ingredients, just like conventional beverages. The natural carbohydrates mentioned above may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a sweetener, a natural sweetener such as thaumatin or stevia extract, or a synthetic sweetener such as saccharin or aspartame may be used. The proportion of the natural carbohydrate may be about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g, per 100 mL of the beverage according to the present invention.

[0388] In addition to the above, the health functional food composition according to the present invention may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, and carbonating agents used in carbonated beverages. In addition, the health functional food composition according to the present invention may contain fruit pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks. These ingredients may be used independently or in mixtures. The ratio of these additives is not limited, but is generally selected in the range of 0.01 to 0.1 parts by weight relative to 100 parts by weight of the health functional food composition according to the present invention.

[0389]

[0390] Alternatively, the present invention provides a use for a composition for preventing, treating or improving gastrointestinal inflammatory diseases or gastric acid-related diseases, comprising the imidazopyridine compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0391] Alternatively, the present invention provides a method for preventing, treating, or improving a gastrointestinal inflammatory disease or a gastric acid-related disease, comprising administering to a subject the imidazopyridine compound or a pharmaceutically acceptable salt thereof. In this case, the term "subject" refers to a subject in need of treatment for a disease, and more specifically, refers to a mammal such as a human or non-human primate, mouse, rat, dog, cat, horse, or cow.

[0392]

[0393] Hereinafter, preferred examples are presented to aid in understanding the present invention. However, the following examples are provided solely to facilitate a better understanding of the present invention, and the scope of the present invention is not limited by the following examples.

[0394]

[0395] <Example>

[0396] [Preliminary Example 1] Preparation of N8-(2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine (Intermediate 1)

[0397]

[0398] Step 1: Preparation of 6-bromo-2,3-dimethylimidazo[1,2-a]pyridin-8-amine

[0399] Tetrahydrofuran (212 mL) was added to 5-bromopyridine-2,3-diamine (20 g, 106 mmol), and 3-bromo-2-butanone (12.9 mL, 127 mmol) was added at room temperature, followed by stirring at 100°C for 2 hours. After completion of the reaction, the mixture was cooled to room temperature. The precipitated solid was filtered and dried to obtain the target compound (21.4 g, 84.4%).

[0400] Step 2: Preparation of 6-bromo-N-(2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridin-8-amine

[0401] The compound prepared in Step 1 (10 g, 41.84 mmol) was dissolved in isopropyl alcohol (418 ml). Potassium carbonate (14.4 g, 104.6 mmol) and sodium iodide (6.2 g, 41.8 mmol) were added, and the mixture was stirred at room temperature. 2-(chloromethyl)-1,3-dimethylbenzene (7 g, 46 mmol) was added, and the mixture was stirred at 70°C for 3 hours. Upon completion of the reaction, the mixture was cooled to room temperature, dichloromethane and distilled water were added, and the layers were separated. The organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (9.6 g, 64.2%).

[0402] Step 3: Preparation of N-(2,6-dimethylbenzyl)-6-((diphenylmethylene)amino)-2,3-dimethylimidazo[1,2-a]pyridin-8-amine

[0403] The compound prepared in step 2 (9.5 g, 26.6 mmol) was dissolved in toluene (133 ml). Diphenylmethanimine (5.7 g, 31.9 mmol), tris(dibenzylideneacetone)dipalladium (2.4 g, 2.66 mmol), (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (3.3 g, 5.32 mmol), and sodium tert-butoxide (7.6 g, 79.8 mmol) were added and stirred at 80°C for 12 hours. After the reaction was completed, it was cooled to room temperature, and dichloromethane and distilled water were added to separate the layers. The organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (8.4 g, 68.9%).

[0404] Step 4: Preparation of N8-(2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride

[0405] The compound prepared in step 3 (8.4 g, 18.3 mmol) was dissolved in ethyl acetate (91.5 ml). 4 N hydrochloric acid (36.6 mL, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 12 hours. After the reaction was completed, the mixture was filtered and dried to obtain the target compound (5.8 g, 96%).

[0406] 1 H NMR (500 MHz, DMSO-d6) δ 7.20-7.11 (m, 4H), 6.58 (s, 1H), 6.21 (s, 1H), 4.28 (s, 2H), 2.36 (s, 3H), 2.34 (s, 6H), 2.33 (s, 3H)

[0407]

[0408] [Preliminary Example 2] Preparation of N8-(4-fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (Intermediate 2)

[0409]

[0410] Step 1: Preparation of 6-bromo-N-(4-fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridin-8-amine

[0411] The compound (2.0 g, 8.36 mmol) prepared in Step 1 of Preparatory Example 1 was dissolved in acetonitrile (83.6 ml). Potassium carbonate (3.4 g, 25.08 mmol) and sodium iodide (1.2 g, 8.36 mmol) were added, and the mixture was heated and stirred at 70°C. 2-(Bromomethyl)-5-fluoro-1,3-dimethylbenzene (2.16 g, 10.03 mmol) was added, and the mixture was stirred at 70°C for 3 hours. Upon completion of the reaction, the mixture was cooled to room temperature, dichloromethane and distilled water were added, and the layers were separated. The organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (1.6 g, 50%).

[0412] Step 2: Preparation of 6-((diphenylmethylene)amino)-N-(4-fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridin-8-amine

[0413] The compound prepared in Step 1 (1.4 g, 3.72 mmol) was dissolved in toluene (19 ml). Diphenylmethanimine (808 mg, 4.46 mmol), tris(dibenzylideneacetone)dipalladium (338 mg, 0.37 mmol), (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (462 mg, 0.74 mmol), and sodium tert-butoxide (1.07 g, 11.16 mmol) were added and stirred at 80°C for 12 hours. After the reaction was completed, the mixture was cooled to room temperature, dichloromethane and distilled water were added, and the layers were separated. The organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (1.5 g, 84%).

[0414] Step 3: Preparation of N8-(4-fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride

[0415] The compound prepared in step 2 above (1.5 g, 3.15 mmol) was dissolved in ethyl acetate (15.7 ml). 4 N hydrochloric acid (6.3 ml, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 12 hours. After the reaction was completed, the mixture was filtered and dried to obtain the target compound (1.0 g, 77%).

[0416] 1 H NMR (500 MHz, DMSO-d6) δ 13.16 (s, 1H), 7.24-7.14 (d, 1H), 7.07-6.96 (m, 2H), 6.53 (s, 1H), 5.99-5.98 (m, 1H), 4.24-4.23 (d, 2H), 2.40-2.32 (m, 12H)

[0417]

[0418] [Example 1] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclopentanecarboxamide

[0419]

[0420] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (59.0 mg, 0.15 mmol), diisopropylethylamine (0.06 mL, 0.36 mmol), and cyclopentanecarboxylic acid (14.0 mg, 0.13 mmol) were added, and the mixture was stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was depressurized and concentrated, and purified by column chromatography to obtain the target compound (10 mg, 21%).

[0421] 1 H NMR (500 MHz, CDCl3) δ 8.25 (s, 1H), δ 7.13-7.10 (t, 1H), 7.05-7.02 (m, 3H), 5.90 (s, 1H), 4.84 (s, 1H), 4.31-4.30 (d, 2H), 2.74-2.70 (m, 1H), 2.37 (s, 3H), 2.33 (s, 6H), 2.31 (s, 3H), 2.04-1.97 (m, 4H), 1.84-1.81 (m, 2H), 1.67-1.64 (m, 2H)

[0422]

[0423] [Example 2] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclopropanecarboxamide

[0424]

[0425] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. Triethylamine (0.05 mL, 0.36 mmol) and cyclopropanecarbonyl chloride (12.0 mg, 0.12 mmol) were added and stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (15 mg, 34%).

[0426] 1 H NMR (500 MHz, CDCl3) δ 8.17 (s, 1H), δ 7.37 (s, 1H), 7.13-7.10 (t, 1H), 5.95 (s, 1H), 4.88 (s, 1H), 4.30-4.29 (d, 2H), 2.36 (s, 6H), 2.31 (s, 6H), δ 1.54 (s, 1H), 1.11-1.10 (m, 2H), 0.88-0.86 (m, 2H)

[0427]

[0428] [Example 3] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclohexanecarboxamide

[0429]

[0430] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. Triethylamine (0.05 mL, 0.36 mmol) and cyclohexanecarbonyl chloride (12.0 mg, 0.12 mmol) were added and stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (13 mg, 26%).

[0431] 1 H NMR (500 MHz, CDCl3) δ 8.25 (s, 1H), 7.13-7.10 (m, 1H), 7.07-7.03 (m, 3H), 5.89 (s, 1H), 4.84 (s, 1H), 4.30-4.29 (d, 2H), 2.36 (s, 3H), 2.33 (s, 6H), 2.31 (s, 3H), 2.27-2.26 (m, 2H), 2.04-2.01 (m, 2H), 1.98-1.87 (m, 2H), 1.74-1.72 (m, 2H), 1.59-1.57 (m, 2H), 1.35-1.30 (m, 2H)

[0432]

[0433] [Example 4] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide

[0434]

[0435] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50.0 mg, 0.15 mmol) was dissolved in dichloromethane. Triethylamine (0.03 mL, 0.22 mmol) and acetic anhydride (0.01 mL, 0.16 mmol) were added and stirred at room temperature for 6 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (10 mg, 19%).

[0436] 1 H NMR (500 MHz, CDCl3) δ 8.14 (s, 1H), 7.12-7.10 (m, 1H), 7.04-7.03 (m, 3H), 5.91 (s, 1H), 4.88 (s, 1H), 4.30-4.29 (d, 2H), 2.36-2.32 (m, 12H), δ 2.22 (s, 3H)

[0437]

[0438] [Example 5] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclobutanecarboxamide

[0439]

[0440] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. Triethylamine (0.05 mL, 0.36 mmol) and cyclobutanecarbonyl chloride (14.0 mg, 0.12 mmol) were added and stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (11 mg, 24%).

[0441] 1 H NMR (500 MHz, CDCl3) δ 8.26 (s, 1H), δ 7.13-7.10 (m, 1H), 7.05-7.03 (d, 2H), 6.90 (s, 1H), 5.90 (s, 1H), 4.88 (s, 1H), 4.30 (s, 2H), 3.21-3.18 (m, 1H), 2.45-2.43 (m, 2H), 2.39-2.34 (m, 12H), 2.28-2.26 (m, 2H)

[0442]

[0443] [Example 6] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-1-carboxamide

[0444]

[0445] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50.0 mg, 0.15 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (24.0 mg, 0.15 mmol), triethylamine (0.04 mL, 0.3 mmol), and azetidine (0.01 mL, 0.15 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (6 mg, 10%).

[0446] 1 H NMR (500 MHz, CDCl3) δ 7.94 (s, 1H), δ 7.11-7.10 (m, 2H), 7.04-7.02 (m, 2H), 5.96-5.90 (m, 1H), 5.87-5.77 (m, 1H), 4.30-4.29 (d, 2H), 4.17-4.07 (m, 6H), 2.40-2.36 (m, 6H), 2.34-2.31 (m, 6H)

[0447]

[0448] [Example 7] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)isobutyramide

[0449]

[0450] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50.0 mg, 0.15 mmol) was dissolved in dichloromethane. Triethylamine (0.08 mL, 0.60 mmol) and isobutyryl chloride (16.0 mg, 0.16 mmol) were added and stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (10 mg, 18%).

[0451] 1 H NMR (500 MHz, CDCl3) δ 8.29 (s, 1H), 7.13-7.02 (m, 4H), 5.95 (s, 1H, 4.83 (s, 1H), 4.30 (d, 2H), 2.36-2.33 (m, 12H), 1.30-1.25 (m, 6H)

[0452]

[0453] [Example 8] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)pivalamide

[0454]

[0455] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50.0 mg, 0.15 mmol) was dissolved in dichloromethane. 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (85.0 mg, 0.22 mmol), diisopropylethylamine (0.1 mL, 0.60 mmol), and pivalic acid (16.0 mg, 0.16 mmol) were added, and the mixture was stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was depressurized and concentrated, and purified by column chromatography to obtain the target compound (8 mg, 14%).

[0456] 1 H NMR (500 MHz, CDCl3) δ 8.59 (s, 1H), 7.85 (s, 1H), 6.74 (s, 2H), 6.67 (s, 2H), 4.30-4.29 (d, 2H), 2.39-2.22 (m, 9H), 1.40-1.39 (m, 12H)

[0457]

[0458] [Example 9] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2,2-difluoroacetamide

[0459]

[0460] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50.0 mg, 0.15 mmol) was dissolved in dichloromethane. 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (85.0 mg, 0.22 mmol), diisopropylethylamine (0.1 mL, 0.60 mmol), and 2,2-difluoroacetic acid (15.0 mg, 0.16 mmol) were added, and the mixture was stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was depressurized and concentrated, and purified by column chromatography to obtain the target compound (10 mg, 17%).

[0461] 1 H NMR (500 MHz, CDCl3) δ 8.13 (s, 1H), 7.82-7.78 (m, 1H), 7.06-7.01 (m, 1H), 6.99-6.95 (m, 2H), 6.11-5.89 (m, 2H), 4.25-4.24 (d, 2H), 2.29-2.27 (m, 12H), 1.18 (s, 1H)

[0462]

[0463] [Example 10] Preparation of 2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide hydrochloride

[0464]

[0465] Step 1: Preparation of tert-butyl (2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)carbamate

[0466] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50.0 mg, 0.15 mmol) was dissolved in dichloromethane. 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (85.0 mg, 0.22 mmol), diisopropylethylamine (0.1 mL, 0.60 mmol), and (tert-butoxycarbonyl)glycine (28.0 mg, 0.16 mmol) were added and stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was depressurized and concentrated, and purified by column chromatography to obtain the target compound (35 mg, 85%).

[0467] Step 2: Preparation of 2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide hydrochloride

[0468] Tert-Butyl (2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)carbamate (30.0 mg, 0.06 mmol) was dissolved in ethyl acetate. 4 N hydrochloric acid (0.16 ml, 0.4 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 6 h. After the reaction was completed, the mixture was filtered to obtain the target compound (9 mg, 38%).

[0469] 1 H NMR (500 MHz, DMSO-d6) δ 11.21 (s, 1H), 8.42 (s, 1H), 8.26 (m, 3H), 7.22-7.13 (m, 3H), 6.96 (s, 1H), 6.47 (s, 1H), 4.31-4.30 (d, 2H), 3.89-3.88 (d, 2H), 2.42-2.36 (m, 12H)

[0470]

[0471] [Example 11] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)pyrrolidine-1-carboxamide

[0472]

[0473] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (19.0 mg, 0.12 mmol), triethylamine (0.06 mL, 0.24 mmol), and pyrrolidine (17 mg, 0.24 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (6 mg, 12%).

[0474] 1 H NMR (500 MHz, CDCl3) δ 7.14-7.12 (m, 2H), 7.08-7.07 (m, 2H), 7.02-7.01 (m, 2H), 4.95-4.94 (d, 2H), 2.45-2.43 (m, 9H), 2.39-2.38 (m, 3H), 2.19-2.03 (m, 8H)

[0475]

[0476] [Example 12] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)bicyclo[1.1.1]pentane-1-carboxamide

[0477]

[0478] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (Intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (68.0 mg, 0.18 mmol), diisopropylethylamine (0.06 mL, 0.48 mmol), and bicyclo[1.1.1]pentane-1-carboxylic acid (14.0 mg, 0.13 mmol) were added and stirred at room temperature for 6 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (8 mg, 17%).

[0479] 1 H NMR (500 MHz, CDCl3) δ 8.27 (s, 1H), 7.16-7.07 (m, 1H), 7.06-7.03 (m, 3H), 5.95 (s, 1H), 4.85 (s, 1H), 4.35-4.34 (d, 2H), 2.39-2.35 (m, 12H), 2.21 (m, 7H)

[0480]

[0481] [Example 13] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)propionamide

[0482]

[0483] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 20.0 mg, 0.06 mmol) was dissolved in dichloromethane. Triethylamine (0.02 mL, 0.18 mmol) and propionyl chloride (5.0 mg, 0.06 mmol) were added and stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (6 mg, 28%).

[0484] 1 H NMR (500 MHz, CDCl3) δ 8.22 (s, 1H), 7.14-7.12 (m, 2H), 7.05-7.04 (m, 1H), 5.91 (s, 1H), 4.85 (s, 1H), 4.32-4.31 (d, 2H), 2.47-2.42 (m, 2H), 2.34-2.32 (m, 12H), 1.31-1.28 (m, 3H)

[0485]

[0486] [Example 14] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)oxazole-2-carboxamide

[0487]

[0488] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (34.0 mg, 0.15 mmol), 1-hydroxybenzotriazole hydrate (24.0 mg, 0.15 mmol), triethylamine (0.06 mL, 0.48 mmol), and oxazole-2-carboxylic acid (14.0 mg, 0.13 mmol) were added and stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was depressurized and concentrated, and purified by column chromatography to obtain the target compound (6 mg, 12%).

[0489] 1 H NMR (500 MHz, DMSO-d6) δ 10.77 (s, 1H), 8.44 (s, 1H), 8.28 (s, 1H), 7.58 (s, 1H), 7.17-7.08 (m, 3H), 6.74 (s, 1H), 5.04-5.02 (m, 1H), 4.33-4.32 (d, 2H), 2.36-2.23 (m, 12H)

[0490]

[0491] [Example 15] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methoxyacetamide

[0492]

[0493] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. Triethylamine (0.04 mL, 0.30 mmol) and 2-methoxyacetyl chloride (14.0 mg, 0.13 mmol) were added and stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (9 mg, 20%).

[0494] 1 H NMR (500 MHz, CDCl3) δ 8.22 (s, 1H), 8.13 (s, 1H), 7.14-7.11 (m, 1H), 7.05-7.04 (m, 2H), 4.85 (s, 1H), 4.34-4.33 (d, 2H), 4.06 (s, 2H), 3.55 (s, 3H), 2.38-2.33 (m, 12H)

[0495]

[0496] [Example 16] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2,2-difluoropropanamide

[0497]

[0498] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (34.0 mg, 0.15 mmol), 1-hydroxybenzotriazole hydrate (24.0 mg, 0.15 mmol), triethylamine (0.06 mL, 0.48 mmol), and 2,2-difluoropropanoic acid (14.0 mg, 0.13 mmol) were added and stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (9 mg, 19%).

[0499] 1 H NMR (500 MHz, CDCl3) δ 8.19 (s, 1H), 7.85 (s, 1H), 7.15-7.12 (m, 1H), 7.06-7.04 (m, 2H), 4.99 (s, 1H), 4.93 (s, 1H), 4.34-4.33 (d, 2H), 2.38-2.33 (m, 12H), 1.98-1.90 (m, 3H)

[0500]

[0501] [Example 17] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-fluorocyclobutane-1-carboxamide

[0502]

[0503] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (34.0 mg, 0.15 mmol), 1-hydroxybenzotriazole hydrate (24.0 mg, 0.15 mmol), triethylamine (0.06 mL, 0.48 mmol), and 3-fluorocyclobutane-1-carboxylic acid (15.0 mg, 0.13 mmol) were added and stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was depressurized and concentrated, and purified by column chromatography to obtain the target compound (10 mg, 21%).

[0504] 1 H NMR (500 MHz, CDCl3) δ 8.23 ​​(s, 1H), 7.14-7.11 (m, 1H), 7.05-7.04 (m, 2H), 6.97 (s, 1H), 5.04-4.87 (m, 2H), 4.31-4.30 (d, 2H), 2.68-2.58 (m, 4H), 2.37-2.32 (m, 12H)

[0505]

[0506] [Example 18] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclobutanesulfonamide

[0507]

[0508] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. Triethylamine (0.04 mL, 0.30 mmol) and cyclobutanesulfonyl chloride (20.0 mg, 0.13 mmol) were added and stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (8 mg, 16%).

[0509] 1 H NMR (500 MHz, CDCl3) δ 7.16-7.13 (m, 2H), 7.08-7.05 (m, 4H), 5.92 (s, 1H), 5.03 (s, 1H), 4.38-4.36 (m, 2H), 3.42-3.40 (m, 1H), 2.42 (s, 6H), 2.40-2.43 (m, 4H), 1.66 (s, 3H)

[0510]

[0511] [Example 19] Preparation of (S)-2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)propanamide hydrochloride

[0512]

[0513] Step 1: Preparation of tert-butyl (S)-(1-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl)carbamate

[0514] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (59.0 mg, 0.15 mmol), diisopropylethylamine (0.08 mL, 0.48 mmol), and (tert-butoxycarbonyl)-L-alanine (24.0 mg, 0.13 mmol) were added and stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was depressurized and concentrated, and purified by column chromatography to obtain the target compound (10 mg, 17%).

[0515] Step 2: Preparation of (S)-2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)propanamide hydrochloride

[0516] Tert-butyl (S)-(1-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl)carbamate (10.0 mg, 0.02 mmol) prepared in Step 1 above was dissolved in ethyl acetate. 4 N hydrochloric acid (0.04 ml, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 6 hours. After the reaction was completed, the mixture was filtered to obtain the target compound (4 mg, 47%).

[0517] 1 H NMR (500 MHz, DMSO-d6) δ 13.89 (s, 1H), 11.31 (s, 1H), 8.47 (s, 1H), 8.38-8.37 (m, 3H), 4.31-4.30 (d, 2H), 4.17-4.14 (m, 1H), 2.51-2.41 (m, 15H)

[0518]

[0519] [Example 20] Preparation of (R)-2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)propanamide hydrochloride

[0520]

[0521] Step 1: Preparation of tert-butyl (R)-(1-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl)carbamate

[0522] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (59.0 mg, 0.15 mmol), diisopropylethylamine (0.08 mL, 0.48 mmol), and (tert-butoxycarbonyl)-D-alanine (24.0 mg, 0.13 mmol) were added and stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was depressurized and concentrated, and purified by column chromatography to obtain the target compound (14 mg, 25%).

[0523] Step 2: Preparation of (R)-2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)propanamide hydrochloride

[0524] Tert-butyl (R)-(1-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl)carbamate (10.0 mg, 0.02 mmol) prepared in Step 1 above was dissolved in ethyl acetate. 4 N hydrochloric acid (0.04 ml, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 6 hours. After the reaction was completed, the mixture was filtered to obtain the target compound (4 mg, 47%).

[0525] 1 H NMR (500 MHz, DMSO-d6) δ 13.86 (s, 1H), 11.29 (s, 1H), 8.46 (s, 1H), 8.37-8.36 (m, 3H), 7.23-7.21 (m, 1H), 7.16-7.14 (m, 2H), 7.05 (s, 1H), 6.45 (s, 1H), 4.31-4.30 (d, 2H), 4.16 (s, 1H), 2.51-2.37 (m, 15H)

[0526]

[0527] [Example 21] Preparation of N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide

[0528]

[0529] N 8 -(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 2, 47 mg, 0.13 mmol) and triethylamine (0.04 ml, 0.27 mmol) were dissolved in dimethylformamide (2 ml). Acetic anhydride (0.02 ml, 0.20 mmol) was added and stirred at room temperature for 2 hours. When the reaction was complete, a saturated aqueous sodium bicarbonate solution was added to precipitate a solid, which was filtered and dried to obtain the target compound (25 mg, 54%).

[0530] 1H NMR (500 MHz, DMSO-d6) δ 9.86 (s, 1H), 8.17 (s, 1H), 6.98-6.94 (m, 3H), 6.20 (s, 1H), 5.09-5.08 (m, 1H), 4.49-4.48 (m, 1H), 4.25-4.25 (d, 2H), 2.36-2.21 (m, 12H), 2.07 (s, 3H)

[0531]

[0532] [Example 22] Preparation of 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-ethylurea

[0533]

[0534] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (19.0 mg, 0.12 mmol), triethylamine (0.06 mL, 0.24 mmol), and ethylamine diluted in methanol (16 mg, 0.36 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (7 mg, 15%).

[0535] 1 H NMR (500 MHz, CDCl3) δ 7.16-7.13 (m, 2H), 7.08-7.03 (m, 4H), 6.02 (s, 1H), 4.30-4.28 (m, 2H), 3.33-3.30 (m, 2H), 2.34-2.22 (m, 12H), 1.18-1.15 (m, 3H)

[0536]

[0537] [Example 23] Preparation of 1-cyclobutyl-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea hydrochloride

[0538]

[0539] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (19.0 mg, 0.12 mmol), triethylamine (0.06 mL, 0.24 mmol), and cyclobutylamine (8 mg, 0.12 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (19 mg, 40%). After dissolving in ethyl acetate and adding 4 N hydrochloric acid (0.04 mL, 0.5 M) dissolved in 1,4-dioxane, the mixture was stirred at room temperature for 12 hours. After the reaction was completed, the mixture was filtered to obtain the hydrochloride salt of the target compound.

[0540] 1 H NMR (500 MHz, DMSO-d6) δ 13.35 (s, 1H), 8.83 (s, 1H), 8.30 (s, 1H), 7.23-20 (m, 1H), 7.16-7.14 (m, 2H), 6.77-6.75 (m, 2H), 6.13 (s, 1H), 4.31-4.30 (d, 2H), 2.38-2.36 (m, 12H), 2.24-2.22 (m, 2H), 2.20-2.19 (m, 1H), 1.93-1.91 (m, 2H), 1.65-1.62 (m, 2H)

[0541]

[0542] [Example 24] Preparation of 1-cyclopropyl-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea hydrochloride

[0543]

[0544] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50.0 mg, 0.15 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (24.0 mg, 0.15 mmol), triethylamine (0.04 mL, 0.3 mmol), and cyclopropylamine (8 mg, 0.15 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (20 mg, 35%). 4 N hydrochloric acid (0.04 mL, 0.5 M) dissolved in ethyl acetate and 1,4-dioxane was added and stirred at room temperature for 12 h. After the reaction was completed, the hydrochloride salt of the target compound was obtained by filtration.

[0545] 1 H NMR (500 MHz, DMSO-d6) δ 13.47 (s, 1H), 8.90 (s, 1H), 8.34 (s, 1H), 7.23-7.21 (m, 1H), 7.19-7.15 (m, 2H), 6.83-6.81 (m, 2H), 4.31-4.30 (d, 2H), 2.37-2.29 (m, 12H), 0.67-0.65 (m, 2H), 0.52-0.50 (m, 2H)

[0546]

[0547] [Example 25] Preparation of 2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl acetate

[0548]

[0549] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50.0 mg, 0.15 mmol) was dissolved in dichloromethane. Triethylamine (0.06 mL, 0.45 mmol) and 2-chloro-2-oxoethyl acetate (22.0 mg, 0.16 mmol) were added, and the mixture was stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (10 mg, 16%).

[0550] 1 H NMR (500 MHz, CDCl3) δ 8.15 (s, 1H), 7.64 (s, 1H), 7.15-7.13 (m, 1H), 7.06-7.04 (m, 2H), 5.95 (s, 1H), 4.91 (s, 1H), 4.74 (s, 2H), 4.34-4.33 (d, 2H), 2.38-2.33 (m, 12H), 2.29 (s, 3H)

[0551]

[0552] [Example 26] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-hydroxyacetamide

[0553]

[0554] 2-((8-((2,6-Dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl acetate (15.0 mg, 0.03 mmol) was dissolved in tetrahydrofuran (0.1 ml, 0.3 M), ethanol (0.1 ml, 0.3 M), and distilled water (0.1 ml, 0.3 M). Potassium hydroxide (6.0 mg, 0.11 mmol) was added and stirred at room temperature for 16 h. After the reaction was completed, the pressure was reduced, the solvent was removed, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (5 mg, 47%).

[0555] 1 H NMR (500 MHz, DMSO-d6) δ 13.45 (s, 1H), 10.06 (s, 1H), 8.61 (s, 1H), 7.23-7.20 (m, 1H), 7.16-7.14 (m, 2H), 5.92 (s, 1H), 4.32-4.31 (d, 2H), 4.09-4.08 (d, 2H), 2.41-2.37 (m, 12H)

[0556]

[0557] [Example 27] Preparation of 2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methylpropanamide hydrochloride

[0558]

[0559] Step 1: Preparation of tert-butyl (1-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-methyl-1-oxopropan-2-yl)carbamate

[0560] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (Intermediate 1, 45.0 mg, 0.13 mmol) was dissolved in dichloromethane. 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (64.0 mg, 0.16 mmol), diisopropylethylamine (0.09 mL, 0.52 mmol), and 2-((tert-butoxycarbonyl)amino)-2-methylpropanoic acid (30.0 mg, 0.14 mmol) were added and stirred at room temperature for 6 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (16 mg, 25%).

[0561] Step 2: Preparation of 2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methylpropanamide hydrochloride

[0562] Tert-butyl (1-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-methyl-1-oxopropan-2-yl)carbamate (15.0 mg, 0.03 mmol) prepared in Step 1 above was dissolved in ethyl acetate. 4 N hydrochloric acid (0.06 ml, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 6 hours. After the reaction was completed, the mixture was filtered to obtain the target compound (10 mg, 77%).

[0563] 1 H NMR (500 MHz, DMSO-d6) δ 13.74 (s, 1H), 10.65 (s, 1H), 8.48-8.44 (m, 4H), 7.29-7.15 (m, 4H), 4.32-4.31 (d, 2H), 2.43-2.37 (m, 12H), 1.69 (s, 6H)

[0564]

[0565] [Example 28] Preparation of 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidin-2-one

[0566]

[0567] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.14 mmol) and triethylamine (0.06 mL, 0.43 mmol) were dissolved in tetrahydrofuran (2 mL) and dimethylformamide (1 mL), and the mixture was stirred at room temperature for 10 minutes. 3-Bromopropionyl chloride (0.16 mmol) was slowly added dropwise, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (12 mg, 25%).

[0568] 1 H NMR (500 MHz, CDCl3) δ 7.14-7.11 (m, 2H), 7.05-7.04 (m, 2GH), 5.70 (s, 1H), 4.90 (sm 1H), 4.31-4.30 (m, 2H), 3.57-3.54 (t, 2H), 2.78-2.75 (t, 2H), 2.63 (s, 3H), 2.38 (s, 6H), 2.30 (s, 3H)

[0569]

[0570] [Example 29] Preparation of 1-(bicyclo[1.1.1]pentan-1-yl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea hydrochloride

[0571]

[0572] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 80.0 mg, 0.24 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (38.0 mg, 0.24 mmol), triethylamine (0.06 mL, 0.48 mmol), and bicyclo[1.1.1]pentan-1-amine hydrochloride (28 mg, 0.24 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (10 mg, 10%). After dissolving in ethyl acetate and adding 4 N hydrochloric acid (0.12 mL, 0.2 M) dissolved in 1,4-dioxane, the mixture was stirred at room temperature for 12 hours. After the reaction was completed, the mixture was filtered to obtain the hydrochloride salt of the target compound.

[0573] 1 H NMR (500 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.30 (s, 1H), 7.22-7.19 (m, 2H), 7.15-7.11 (m, 2H), 6.71 (s, 1H), 6.19 (s, 1H), 4.31-4.30 (d, 2H), 2.43-2.36 (m, 14H), 2.02 (s, 6H)

[0574]

[0575] [Example 30] Preparation of 1-(cyclopropylmethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea hydrochloride

[0576]

[0577] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40.0 mg, 0.12 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (19.0 mg, 0.12 mmol), triethylamine (0.03 mL, 0.24 mmol), and cyclopropylmethylamine (8.0 mg, 0.12 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (10 mg, 21%). 4 N hydrochloric acid (0.05 mL, 0.5 M) dissolved in ethyl acetate and 1,4-dioxane was added and stirred at room temperature for 12 h. After the reaction was completed, the hydrochloride salt of the target compound was obtained by filtration.

[0578] 1 H NMR (500 MHz, DMSO-d6) δ 13.44 (s, 1H), 9.04 (s, 1H), 8.31 (s, 1H), 7.22-7.19 (m, 3H), 6.73 (s, 1H), 6.57 (s, 1H), 6.18 (s, 1H), 4.30-4.29 (d, 2H), 3.02-2.99 (t, 2H), 2.21-2.19 (m, 12H), 0.98-0.95 (m, 1H) 0.44-0.43 (m, 2H), 0.21-0.20 (m, 2H)

[0579]

[0580] [Example 31] Preparation of 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-isopropylurea hydrochloride

[0581]

[0582] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 80.0 mg, 0.24 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (14.0 mg, 0.24 mmol), triethylamine (0.06 mL, 0.48 mmol), and isopropylamine (14.0 mg, 0.24 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (8 mg, 8%). 4 N hydrochloric acid (0.1 mL, 0.5 M) dissolved in ethyl acetate and 1,4-dioxane was added and stirred at room temperature for 12 h. After the reaction was completed, the hydrochloride salt of the target compound was obtained by filtration.

[0583] 1 H NMR (500 MHz, DMSO-d6) δ 13.41 (s, 1H), 8.86 (s, 1H), 8.31 (s, 1H), 7.23-7.20 (m, 1H), 7.15-7.14 (m, 2H), 6.71 (s, 1H), 6.38-6.36 (d, 1H), 6.17 (s, 1H), 4.31-4.30 (d, 2H), 3.80-3.78 (m, 1H), 2.39-2.37 (m, 12H), 1.14-1.12 (m, 6H)

[0584]

[0585] [Example 32] Preparation of 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-ethyl-1-methylurea hydrochloride

[0586]

[0587] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 60.0 mg, 0.18 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (29.1 mg, 0.18 mmol), triethylamine (0.07 mL, 0.54 mmol), and N-methylethanamine (10.0 mg, 0.18 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (13 mg, 19%). 4 N hydrochloric acid (0.3 mL, 0.5 M) dissolved in ethyl acetate and 1,4-dioxane was added and stirred at room temperature for 12 h. After the reaction was completed, the hydrochloride salt of the target compound was obtained by filtration.

[0588] 1 H NMR (500 MHz, DMSO-d6) δ 13.42 (s, 1H), 8.59 (s, 1H), 8.39 (s, 1H), 7.23-7.20 (m, 2H), 7.15-7.14 (m, 2H), 6.12 (s, 1H), 4.31-4.30 (d, 2H), 3.41-3.40 (m, 2H), 2.99 (s, 3H), 2.39-2.37 (m, 12H), 1.12-1.10 (t, 3H)

[0589]

[0590] [Example 33] Preparation of 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-ethyl-1-methylurea hydrochloride

[0591]

[0592] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 60.0 mg, 0.18 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (29.1 mg, 0.18 mmol), triethylamine (0.07 mL, 0.54 mmol), and methylamine (14.0 mg, 0.45 mmol) diluted 40% in methanol were added, and the mixture was stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (35 mg, 55%). 4 N hydrochloric acid (0.3 mL, 0.5 M) dissolved in ethyl acetate and 1,4-dioxane was added and stirred at room temperature for 12 h. After the reaction was completed, the hydrochloride salt of the target compound was obtained by filtration.

[0593] 1 H NMR (500 MHz, DMSO-d6) δ 13.35 (s, 1H), 9.04 (s, 1H), 8.33 (s, 1H), 7.23-7.20 (m, 1H), 7.16-7.14 (m, 2H), 6.79 (s, 1H), 6.36-6.35 (m, 1H), 6.13 (s, 1H), 4.30-4.29 (d, 2H), 2.69-2.68 (m, 3H), 2.39-2.37 (m, 12H)

[0594]

[0595] [Example 34] Preparation of ethyl 3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-3-oxopropanoate

[0596]

[0597] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.14 mmol) was dissolved in dichloromethane (2 mL). Ethyl hydrogen malonate (22 mg, 0.16 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (74 mg, 0.19 mmol), and diisopropylethylamine (0.9 mL, 0.60 mmol) were added dropwise and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (46 mg, 75%).

[0598] 1 H NMR (500 MHz, CDCl3) δ 9.26 (s, 1H), 8.21 (s, 1H), 7.12-7.10 (m, 1H), 7.05-7.02 (m, 2H), 6.06 (s, 1H), 4.88 (s, 1H), 4.32-4.28 (m, 4H), 3.53(s, 2H), 2.35-2.31 (m, 12H), 1.37-1.34 (t, 3H)

[0599]

[0600] [Example 35] Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide hydrochloride

[0601]

[0602] Step 1: Preparation of tert-butyl (S)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)carbamoyl)azetidine-1-carboxylate

[0603] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (Intermediate 1, 50.0 mg, 0.15 mmol) was dissolved in dichloromethane. 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (74.0 mg, 0.19 mmol), diisopropylethylamine (0.1 mL, 0.60 mmol), (S)-1-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (30.0 mg, 0.15 mmol) were added and stirred at room temperature for 6 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (20 mg, 27%).

[0604] Step 2: Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide hydrochloride

[0605] Tert-butyl (S)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)carbamoyl)azetidine-1-carboxylate (20.0 mg, 0.04 mmol) prepared in Step 1 above was dissolved in ethyl acetate. 4 N hydrochloric acid (0.08 ml, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 6 hours. After the reaction was completed, the mixture was filtered to obtain the target compound (8 mg, 48%).

[0606] 1H NMR (500 MHz, DMSO-d6) δ 13.89 (s, 1H), 11.28 (s, 1H), 9.50 (s, 1H), 9.02 (s, 1H), 8.52 (s, 1H), 7.23-7.20 (m, 1H), 7.05-7.04 (m, 2H), 7.02 (s, 1H), 6.47 (s, 1H), 5.22-5.20 (m, 1H), 4.31-4.30 (m, 2H), 4.05-4.03 (m, 1H), 3.86-3.82 (m, 1H), 2.79-2.77 (m, 1H), 2.43-2.39 (m, 12H)

[0607]

[0608] [Example 36] Preparation of (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide hydrochloride

[0609]

[0610] Step 1: Preparation of tert-butyl (R)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)carbamoyl)azetidine-1-carboxylate

[0611] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (Intermediate 1, 50.0 mg, 0.15 mmol) was dissolved in dichloromethane. 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (74.0 mg, 0.19 mmol), diisopropylethylamine (0.1 mL, 0.60 mmol), (R)-1-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (30.0 mg, 0.15 mmol) were added and stirred at room temperature for 6 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (20 mg, 27%).

[0612] Step 2: Preparation of (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide hydrochloride

[0613] Tert-butyl (R)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)carbamoyl)azetidine-1-carboxylate (20.0 mg, 0.04 mmol) prepared in Step 1 above was dissolved in ethyl acetate. 4 N hydrochloric acid (0.08 ml, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 6 hours. After the reaction was completed, the mixture was filtered to obtain the target compound (8 mg, 48%).

[0614] 1H NMR (500 MHz, DMSO-d6) δ 14.05 (s, 1H), 11.42 (s, 1H), 9.62 (s, 1H), 9.02 (s, 1H), 8.52 (s, 1H), 7.22-7.06 (m, 4H), 6.54 (s, 1H), 5.21-5.20 (m, 1H), 4.31-4.30 (m, 2H), 4.05-4.04 (m, 1H), 3.84-3.81 (m, 1H), 2.42-2.36 (m, 12H)

[0615]

[0616] [Example 37] Preparation of 1-(2-aminoethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea hydrochloride

[0617]

[0618] Step 1: Preparation of tert-butyl (2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)ethyl)carbamate

[0619] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 60.0 mg, 0.18 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (58.0 mg, 0.36 mmol), triethylamine (0.07 mL, 0.54 mmol), and tert-butyl(2-aminoethyl)carbamate (28.0 mg, 0.18 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (20 mg, 23%).

[0620] Step 2: Preparation of 1-(2-aminoethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea hydrochloride

[0621] Tert-butyl (2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)ethyl)carbamate (15.0 mg, 0.03 mmol) prepared in Step 1 above was dissolved in ethyl acetate. 4 N hydrochloric acid (0.6 mL, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 12 h. After the reaction was completed, filtration was performed to obtain the target compound (10 mg, 77%).

[0622] 1 H NMR (500 MHz, DMSO-d6) δ 13.72 (s, 1H), 9.52 (s, 1H), 8.29 (s, 1H), 7.96 (s, 3H), 7.21-7.12 (m, 3H), 6.86-6.84 (m, 2H), 6.33 (s, 1H), 4.30-4.29 (m, 2H), 3.39-3.26 (m, 2H), 2.93-2.90 (m, 2H), 2.41-2.38 (m, 12H)

[0623]

[0624] [Example 38] Preparation of 4-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-4-oxobutanoic acid

[0625]

[0626] 4-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-4-oxobutanoic acid (Example 38, 37 mg, 0.09 mmol) was dissolved in tetrahydrofuran (1 ml), methanol (1 ml), and distilled water (1 ml). Potassium hydroxide (15 mg, 0.26 mmol) was added, and the mixture was stirred at room temperature for 5 hours. The reaction was terminated by adding 1 N aqueous hydrochloric acid solution, and the pH of the mixture was maintained at 2. After extraction with ethyl acetate, the organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The concentrated residue was dried to obtain the target compound (21 mg, 60%).

[0627] 1 H NMR (500 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.21 (s, 1H), 7.16-7.08 (m, 3H), 6.25 (s, 1H), 4.97 (s, 1H), 4.30-4.29 (m, 2H), 2.59-2.55 (m, 2H), 2.34-2.20 (m, 12H)

[0628]

[0629] [Example 39] Preparation of 3-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl)propanoic acid

[0630]

[0631] Tert-Butyl 3-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl)propanoate (Example 40, 30 mg, 0.06 mmol) was dissolved in dichloromethane (2 ml). Trifluoroacetic acid (0.02 ml, 0.30 mmol) was added, and the mixture was stirred at room temperature for 3 hours. After the reaction was completed, the mixture was reduced in pressure and concentrated to obtain the target compound (13 mg, 49%).

[0632] 1H NMR (500 MHz, DMSO-d6) δ 10.35 (s, 1H), 8.53 (s, 1H), 7.23-7.14 (m, 3H), 6.90-6.84 (m, 1H), 6.10-6.08 (m, 1H), 4.31-4.30 (m, 2H), 3.63-3.61 (m, 4H), 2.61-2.50 (m, 2H), 2.46-2.36 (m, 15H)

[0633]

[0634] [Example 40] Preparation of ethyl 4-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-4-oxobutanoate

[0635]

[0636] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.14 mmol) and triethylamine (0.05 ml, 0.35 mmol) were dissolved in dichloromethane (2 mL). Ethyl succinyl chloride (19 mg, 0.16 mmol) was slowly added dropwise and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (42 mg, 62%).

[0637] 1 H NMR (500 MHz, DMSO-d6) δ 8.16 (s, 1H), 7.46 (s, 1H), 7.26-7.03 (m, 3H), 5.92 (s, 1H), 4.91 (s, 2H), 4.31 (s, 2H), 4.22-4.17 (m, 2H), 2.78-2.77 (m, 2H), 2.71-2.70 (m, 2H), 2.37-2.31 (m, 12H), 1.30-1.25 (m, 3H)

[0638]

[0639] [Example 41] Preparation of tert-butyl 3-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl)propanoate

[0640]

[0641] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol) was dissolved in dichloromethane (2 mL). 3-(3-(tert-butoxy)-3-oxopropoxy)propionic acid (28 mg, 0.12 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (74 mg, 0.19 mmol), and diisopropylethylamine (0.9 ml, 0.60 mmol) were added dropwise and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo and the residue was purified by column chromatography to obtain the target compound (34 mg, 46%).

[0642] 1 H NMR (500 MHz, DMSO-d6) δ 8.36 (s, 1H), 7.32-7.01 (m, 3H), 6.31-6.30 (m, 1H), 5.35-5.34 (m, 1H), 4.85 (s, 1H), 4.36-4.35 (m, 2H), 2.71-2.70 (m, 2H), 2.59-2.57 (m, 2H), 1.66-1.62 (m, 12H), 1.42-1.31 (m, 9H)

[0643]

[0644] [Example 42] Preparation of tert-butyl (2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)ethyl)carbamate hydrochloride

[0645]

[0646] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 60.0 mg, 0.18 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (58.0 mg, 0.36 mmol), triethylamine (0.07 mL, 0.54 mmol), and tert-butyl(2-aminoethyl)carbamate (28.0 mg, 0.18 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (20 mg, 23%). 4 N hydrochloric acid (0.6 mL, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 12 h. After the reaction was completed, the hydrochloride salt of the target compound was obtained by filtration.

[0647] 1 H NMR (500 MHz, DMSO-d6) δ 8.52 (s, 1H), 8.44 (s, 1H), 7.21-7.13 (m, 3H), 6.95 (s, 1H), 5.78-5.76 (m, 2H), 4.24-4.23 (m, 2H), 2.35 (s, 12H)

[0648]

[0649] [Example 43] Preparation of 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,1-dimethylurea hydrochloride

[0650]

[0651] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50.0 mg, 0.15 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (48.0 mg, 0.3 mmol), triethylamine (0.06 mL, 0.45 mmol), and 10% dimethylamine diluted in methanol (67.0 mg, 1.5 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (20 mg, 36%). 4 N hydrochloric acid (0.2 mL, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 12 h. After the reaction was completed, the hydrochloride salt of the target compound was obtained by filtration.

[0652] 1 H NMR (500 MHz, DMSO-d6) δ 13.46 (s, 1H), 8.66 (s, 1H), 8.36 (s, 1H), 7.23-7.14 (m, 4H), 6.12 (s, 1H), 4.31-4.30 (m, 2H), 2.99 (s, 6H), 2.38-2.37 (m, 12H)

[0653]

[0654] [Example 44] Preparation of 1-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-methylurea hydrochloride

[0655]

[0656] N 8-(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (Intermediate 2, 70.0 mg, 0.20 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (64.0 mg, 0.4 mmol), triethylamine (0.08 mL, 0.6 mmol), and 40% methylamine diluted in methanol (15.5 mg, 0.5 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (10 mg, 13%). 4 N hydrochloric acid (0.1 mL, 0.2 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 12 h. After the reaction was completed, the hydrochloride salt of the target compound was obtained by filtration.

[0657] 1 H NMR (500 MHz, DMSO-d6) δ 13.74 (s, 1H), 9.16 (s, 1H), 8.32 (s, 1H), 7.01-6.99 (m, 2H), 6.77 (s, 1H), 6.44 (s, 1H), 6.41 (s, 1H), 6.26 (s, 1H), 4.26-4.25 (m, 2H), 2.68 (s, 3H), 2.38-2.37 (m, 12H)

[0658]

[0659] [Example 45] Preparation of N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide hydrochloride

[0660]

[0661] N 8-(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (Intermediate 2, 70.0 mg, 0.2 mmol) was dissolved in dichloromethane. Triethylamine (0.05 mL, 0.4 mmol) and acetic anhydride (0.01 mL, 0.2 mmol) were added, and the mixture was stirred at room temperature for 6 hours. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (45 mg, 60%). 4 N hydrochloric acid (0.25 mL, 0.5 M) dissolved in 1,4-dioxane was added, and the mixture was stirred at room temperature for 12 hours. When the reaction was complete, the solution was filtered to obtain the hydrochloride salt of the target compound.

[0662] 1 H NMR (500 MHz, DMSO-d6) δ 13.67 (s, 1H), 10.38 (s, 1H), 8.47 (s, 1H), 7.02-7.00 (m, 2H), 6.83 (s, 1H), 6.20-6.16 (brs, 1H), 4.26-4.25 (m, 2H), 2.38-2.37 (m, 12H), 2.12 (s, 3H)

[0663]

[0664] [Example 46] Preparation of methyl((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)carbamoyl)glycinate hydrochloride

[0665]

[0666] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50.0 mg, 0.15 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (48.0 mg, 0.3 mmol), triethylamine (0.06 mL, 0.45 mmol), and methyl glycinate (13.0 mg, 0.15 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (10 mg, 16%). 4 N hydrochloric acid (0.04 mL, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 12 hours. After the reaction was completed, the hydrochloride salt of the target compound was obtained by filtration.

[0667] 1 H NMR (500 MHz, DMSO-d6) δ 13.41 (s, 1H), 9.35 (s, 1H), 8.30 (s, 1H), 7.23-7.20 (m, 2H), 7.15-7.14 (m, 1H), 6.82-6.77 (m, 1H), 6.16 (s, 1H), 4.31-4.30 (m, 2H), 3.92-3.91 (m, 2H), 3.66 (s, 3H), 2.38-2.37 (m, 12H)

[0668]

[0669] [Example 47] Preparation of 2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)-N-methylacetamide hydrochloride

[0670]

[0671] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50.0 mg, 0.15 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (48.0 mg, 0.3 mmol), triethylamine (0.06 mL, 0.45 mmol), and 2-amino-N-methylacetamide (13.0 mg, 0.15 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (10 mg, 16%). 4 N hydrochloric acid (0.08 mL, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 12 hours. After the reaction was completed, the hydrochloride salt of the target compound was obtained by filtration.

[0672] 1 H NMR (500 MHz, DMSO-d6) δ 13.57 (s, 1H), 9.32 (s, 1H), 8.30 (s, 1H), 7.91 (s, 1H), 7.22-7.20 (m, 1H), 7.14-7.13 (m, 2H), 6.73 (s, 1H), 6.67-6.65 (m, 2H), 6.24 (s, 1H), 4.31-4.30 (m, 2H), 3.73-3.72 (m, 2H), 2.62 (s, 3H), 2.38-2.37 (m, 12H)

[0673]

[0674] [Example 48] Preparation of 2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)-N,N-dimethylacetamide hydrochloride

[0675]

[0676] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50.0 mg, 0.15 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (48.0 mg, 0.3 mmol), triethylamine (0.06 mL, 0.45 mmol), and 2-amino-N,N-dimethylacetamide (15.0 mg, 0.15 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (11 mg, 17%). 4 N hydrochloric acid (0.04 mL, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 12 hours. After the reaction was completed, the hydrochloride salt of the target compound was obtained by filtration.

[0677] 1 H NMR (500 MHz, DMSO-d6) δ 13.51 (s, 1H), 9.40 (s, 1H), 8.31 (s, 1H), 7.22-7.19 (m, 1H), 7.15-7.13 (m, 2H), 6.71 (s, 1H), 6.59-6.57 (m, 2H), 6.22 (s, 1H), 4.31-4.30 (m, 2H), 3.99-3.98 (m, 2H), 2.97 (s, 3H), 2.87 (s, 3H), 2.38-2.37 (m, 12H)

[0678]

[0679] [Example 49] Preparation of 3-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,1-dimethylurea hydrochloride

[0680]

[0681] N 8-(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (Intermediate 2, 50.0 mg, 0.14 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (46.0 mg, 0.28 mmol), triethylamine (0.06 mL, 0.42 mmol), and 10% dimethylamine diluted in methanol (70.0 mg, 1.43 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (16 mg, 29%). 4 N hydrochloric acid (0.08 mL, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 12 hours. After the reaction was completed, the hydrochloride salt of the target compound was obtained by filtration.

[0682] 1 H NMR (500 MHz, DMSO-d6) δ 13.33 (s, 1H), 8.64 (s, 1H), 8.35 (s, 1H), 7.17 (s, 1H), 7.04-7.02 (m, 2H), 6.05 (s, 1H), 4.27-4.26 (m, 2H), 2.98 (s, 6H), 2.39-2.37 (m, 12H)

[0683]

[0684] [Example 50] Preparation of 1-cyclopropyl-3-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)urea hydrochloride

[0685]

[0686] N 8-(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (Intermediate 2, 50 mg, 0.14 mmol) and 1,1'-carbonyldiimidazole (45 mg, 0.28 mmol) were dissolved in dichloromethane (0.7 mL) and stirred at room temperature for 1 h. Cyclopropanamine (0.009 mL, 0.14 mmol) and triethylamine (0.05 mL, 0.42 mmol) were added and stirred at room temperature for 6 h. The reaction mixture was purified by column chromatography, dissolved in ethyl acetate, and 4 N hydrochloric acid diluted in 1,4-dioxane (0.28 mL) was added and stirred at room temperature for 2 h. The resulting solid was filtered and dried to obtain the target compound (18 mg, 34%).

[0687] 1 H NMR (500 MHz, DMSO-d6) δ 13.42 (s, 1H), 8.80 (s, 1H), 8.32 (s, 1H), 7.03-7.01 (m, 2H), 6.78-6.67 (m, 2H), 6.02 (s, 1H), 4.27-4.26 (m, 2H), 2.98 (s, 6H), 2.38-2.37 (m, 12H), 1.19-1.16 (m, 1H), 0.85-0.68 (m, 2H), 0.45-0.44 (m, 2H)

[0688]

[0689] [Example 51] Preparation of N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)azetidine-1-carboxamide citrate

[0690]

[0691] N 8-(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (Intermediate 2, 80 mg, 0.22 mmol) and 1,1'-carbonyldiimidazole (35 mg, 0.22 mmol) were dissolved in dichloromethane (3.14 mL) and stirred at room temperature for 1 h. Azetidine (0.01 mL, 0.22 mmol) and triethylamine (0.06 mL, 0.44 mmol) were added and stirred at room temperature for 12 h. The reaction mixture was purified by column chromatography to obtain the target compound (10 mg, 11%). This was then dissolved in acetone, citric acid (9 mg, 0.05 mmol) was added, and stirred at room temperature for 12 h. The resulting solid was filtered and dried to obtain the citrate salt of the target compound.

[0692] 1 H NMR (500 MHz, DMSO-d6) δ 8.40 (s, 1H), 8.08 (s, 1H), 6.99-6.97 (m, 2H), 6.67-6.59 (m, 1H), 5.33-5.32 (m, 1H), 4.24-4.23 (m, 2H), 3.99-3.97 (m, 4H), 2.69-2.57 (m, 4H), 2.38-2.35 (m, 12H)

[0693]

[0694] [Example 52] Preparation of 2-acetamido-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide

[0695]

[0696] 2-Amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide (Example 10, 80 mg, 0.23 mmol) and trimethylamine (0.06 ml, 0.45 mmol) were dissolved in dimethylformamide (4 ml). Acetic anhydride (0.03 ml, 0.34 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction was quenched by adding saturated aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The concentrated residue was dissolved in dichloromethane, and a 2 M hydrochloric acid solution (0.5 ml) diluted with diethyl ether was added, and the mixture was stirred at room temperature for 12 hours. The target compound (24 mg, 24%) was obtained by reducing pressure and concentrating.

[0697] 1 H NMR (500 MHz, DMSO-d6) δ 13.70 (s, 1H), 10.47 (s, 1H), 8.50 (s, 1H), 8.34-8.31 (m, 1H), 7.23-7.20 (m, 4H), 6.97 (s, 1H), 4.31-4.30 (m, 2H), 3.93-3.91 (m, 2H), 2.37 (s, 12H), 1.98 (s, 3H)

[0698]

[0699] [Example 53] Preparation of 2-(dimethylamino)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide

[0700]

[0701] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.14 mmol) was dissolved in dichloromethane (2 mL). 2-(Dimethylamino)acetic acid (16 mg, 0.16 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (74 mg, 0.19 mmol), and diisopropylethylamine (0.9 ml, 0.60 mmol) were added dropwise and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (24 mg, 42%).

[0702] 1 H NMR (500 MHz, DMSO-d6) δ 9.74-9.70 (m, 1H), 8.23-8.16 (m, 1H), 7.20-7.08 (m, 4H), 6.67-6.45 (m, 1H), 4.31-4.30 (m, 2H), 2.34 (s, 14H), 1.29-1.27 (m, 6H)

[0703]

[0704] [Example 54] Preparation of 1-butyl-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea

[0705]

[0706] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.14 mmol) and 1,1'-carbonyldiimidazole (49 mg, 0.30 mmol) were dissolved in dichloromethane (2 mL) and stirred at room temperature for 1 h. Triethylamine (0.06 ml, 0.45 mmol) and propylamine hydrochloride (14 mg, 0.15 mmol) were added and stirred at room temperature for 6 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (22 mg, 37%).

[0707] 1 H NMR (500 MHz, DMSO-d6) δ 8.23 ​​(s, 1H), 7.98 (m, 1H), 7.16-7.07 (m, 4H), 6.16-6.14 (m, 1H), 6.07-6.01 (m, 1H), 4.30-4.29 (m, 2H), 3.05-3.04 (m, 2H), 2.35-2.22 (m, 12H), 1.47-1.46 (m, 2H), 0.89-0.86 (m, 3H)

[0708]

[0709] [Example 55] Preparation of N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)pivalamide

[0710]

[0711] 2-Amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide (Example 10, 40 mg, 0.10 mmol) was dissolved in dichloromethane (2 mL). Parvalic acid (11 mg, 0.11 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (51 mg, 0.13 mmol), and diisopropylethylamine (0.07 ml, 0.41 mmol) were added dropwise and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (32 mg, 73%).

[0712] 1 H NMR (500 MHz, DMSO-d6) δ 9.89 (s, 1H), 8.17 (s, 1H), 7.77 (s, 1H), 7.15-7.09 (m, 3H), 6.21 (s, 1H), 5.02 (s, 1H), 4.31-4.30 (m, 2H), 3.87-3.85 (m, 2H), 2.35-2.21 (m, 12H), 1.24 (s, 9H)

[0713]

[0714] [Example 56] Preparation of N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-2,2-difluoroacetamide

[0715]

[0716] 2-Amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide (Example 10, 40 mg, 0.10 mmol) was dissolved in dichloromethane (2 mL). Difluoroacetic acid (11 mg, 0.11 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (51 mg, 0.13 mmol), and diisopropylethylamine (0.07 ml, 0.41 mmol) were added dropwise and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (29 mg, 68%).

[0717] 1 H NMR (500 MHz, DMSO-d6) δ 10.05 (s, 1H), 8.97-8.95 (m, 1H), 8.16 (s, 1H), 7.15-7.08 (m, 3H), 6.22 (s, 1H), 5.03 (s, 1H), 4.31-4.30 (m, 2H), 3.97-3.96 (m, 2H), 2.35-2.28 (m, 12H), 1.83-1.79 (m, 1H)

[0718]

[0719] [Example 57] Preparation of N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-2,2-difluoropropanamide

[0720]

[0721] 2-Amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide (Example 10, 40 mg, 0.10 mmol) was dissolved in dichloromethane (2 mL). 2,2-Difluoropropionic acid (12 mg, 0.11 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (51 mg, 0.13 mmol), and diisopropylethylamine (0.07 ml, 0.41 mmol) were added dropwise and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo and the residue was purified by column chromatography to obtain the target compound (31 mg, 70%).

[0722] 1 H NMR (500 MHz, DMSO-d6) δ 10.06 (s, 1H), 9.15-9.12 (m, 1H), 8.16 (s, 1H), 7.16-7.09 (m, 3H), 6.44-6.24 (m, 1H), 5.06 (s, 1H), 4.31-4.30 (m, 2H), 4.01-4.00 (m, 2H), 2.69 (s, 3H), 2.35-2.28 (m, 12H)

[0723]

[0724] [Example 58] Preparation of N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-3-hydroxycyclobutane-1-carboxamide

[0725]

[0726] 2-Amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide (Example 10, 40 mg, 0.10 mmol) was dissolved in dichloromethane (2 mL). 3-Hydroxycyclobutanecarboxylic acid (12 mg, 0.11 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (51 mg, 0.13 mmol), and diisopropylethylamine (0.07 ml, 0.41 mmol) were added dropwise and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (4 mg, 9%).

[0727] 1 H NMR (500 MHz, DMSO-d6) δ 10.06 (s, 1H), 8.25-8.09 (m, 2H), 7.17-7.10 (m, 3H), 6.42 (s, 1H), 5.11-5.09 (m, 1H), 4.30 (s, 2H), 3.92-3.90 (m, 2H), 2.30-2.28 (m, 12H), 1.99-1.97 (m, 3H), 1.40-1.35 (m, 2H), 1.29-1.20 (m, 2H)

[0728]

[0729] [Example 59] Preparation of N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-3-fluorocyclobutane-1-carboxamide

[0730]

[0731] 2-Amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide (Example 10, 40 mg, 0.10 mmol) was dissolved in dichloromethane (2 mL). 3-Fluorocyclobutanecarboxylic acid (13 mg, 0.11 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (51 mg, 0.13 mmol), and diisopropylethylamine (0.07 ml, 0.41 mmol) were added dropwise and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (23 mg, 51%).

[0732] 1 H NMR (500 MHz, DMSO-d6) δ 9.95-9.93 (m, 1H), 8.28-8.27 (m, 1H), 8.15 (s, 1H), 7.15-7.08 (m, 3H), 6.23 (s, 1H), 5.04-5.01 (m, 1H), 4.30-4.29 (m, 2H), 3.91-3.90 (m, 2H), 2.28-2.21 (m, 12H), 1.26-1.24 (m, 6H)

[0733]

[0734] [Example 60] Preparation of 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)imidazolidine-2,4-dione

[0735]

[0736] 2-Amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide (Example 10, 40 mg, 0.10 mmol) and 1,1'-carbonyldiimidazole (22 mg, 0.10 mmol) were dissolved in dichloromethane (2 mL) and stirred at room temperature for 1 h. Triethylamine (0.06 ml, 0.45 mmol) and a 40% solution of methylamine diluted in methanol (8 mg, 0.26 mmol) were added and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (10 mg, 26%).

[0737] 1 H NMR (500 MHz, DMSO-d6) δ 8.33 (s, 1H), 7.62 (s, 1H), 7.15-7.13 (m, 2H), 7.09-7.07 (m, 1H), 6.21 (s, 1H), 5.08-5.07 (m, 1H), 4.30-4.29 (m, 2H), 4.09 (s, 2H), 2.34-2.32 (m, 9H), 2.25 (s, 3H)

[0738]

[0739] [Example 61] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)morpholine-4-carboxamide citrate

[0740]

[0741] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol) and 1,1'-carbonyldiimidazole (48 mg, 0.30 mmol) were dissolved in dichloromethane (0.7 mL) and stirred at room temperature for 1 h. Morpholine (0.01 mL, 0.15 mmol) and triethylamine (0.06 mL, 0.45 mmol) were added and stirred at room temperature for 6 h. The reaction mixture was purified by column chromatography to obtain the target compound (20 mg, 32%). This was then dissolved in acetone, citric acid (9 mg, 0.05 mmol) was added, and stirred at room temperature for 12 h. The resulting solid was filtered and dried to obtain the citrate salt of the target compound.

[0742] 1 H NMR (500 MHz, DMSO-d6) δ 8.54 (s, 1H), 8.04 (s, 1H), 7.20-7.15 (m, 3H), 6.67-6.60 (m, 1H), 5.33-5.32 (m, 1H), 4.29-4.28 (m, 2H), 3.64-3.62 (m, 4H), 3.47-3.45 (m, 4H), 2.68-2.64 (m, 4H), 2.37-2.36 (m, 12H)

[0743]

[0744] [Example 62] Preparation of 2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)ureido)ethyl acetate hydrochloride

[0745]

[0746] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol) and 1,1'-carbonyldiimidazole (48 mg, 0.30 mmol) were dissolved in dichloromethane (0.7 mL) and stirred at room temperature for 1 h. 2-Aminoethyl acetate (15 mg, 0.15 mmol) and triethylamine (0.06 mL, 0.45 mmol) were added and stirred at room temperature for 6 h. The reaction was quenched by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography, dissolved in ethyl acetate, and 4 N hydrochloric acid (0.3 mL) dissolved in 1,4-dioxane was added, followed by stirring at room temperature for 2 hours. The resulting solid was filtered and dried to obtain the target compound (10 mg, 15%).

[0747] 1 H NMR (500 MHz, DMSO-d6) δ 9.08 (s, 1H), 8.34-8.31 (m, 1H), 7.23-7.14 (m, 3H), 6.76-6.60 (m, 2H), 6.14 (s, 1H), 4.36-4.35 (m, 2H), 4.05-4.01 (m, 2H), 2.38-2.36 (m, 12H), 2.04-1.99 (m, 3H), 1.24-1.17 (m, 2H)

[0748]

[0749] [Example 63] Preparation of (S)-2-amino-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)propanamide hydrochloride

[0750]

[0751] Step 1: Preparation of tert-butyl (S)-(1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl)carbamate

[0752] N 8 -(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 2, 50 mg, 0.14 mmol), tert-Butyl (S)-(1-amino-1-oxopropan-2-yl)carbamate (29 mg, 0.15 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (69 mg, 0.18 mmol), and diisopropylethylamine (0.09 mL, 0.56 mmol) were dissolved in dichloromethane (0.7 mL), and the mixture was stirred at room temperature for 12 h. The reaction was terminated by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, then concentrated under reduced pressure. The residue was purified by column chromatography to obtain the target compound (28 mg, 44%).

[0753] Step 2: Preparation of (S)-2-amino-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)propanamide hydrochloride

[0754] Tert-butyl (R)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)-2-methylazetidine-1-carboxylate (26 mg, 0.053 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.25 mL), and 4 N hydrochloric acid (0.1 mL) diluted in 1,4-dioxane was added, followed by stirring at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (10 mg, 45%).

[0755] 1 H NMR (500 MHz, DMSO-d6) δ 11.32 (s, 1H), 8.44-8.37 (m, 4H), 7.02-7.00 (m, 3H), 4.28-4.27 (m, 2H), 4.05-4.01 (m, 1H), 2.41-2.40 (m, 12H), 1.53-1.51 (m, 3H)

[0756]

[0757] [Example 64] Preparation of 2-amino-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)acetamide hydrochloride

[0758]

[0759] Step 1: Preparation of tert-butyl (2-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)carbamate

[0760] N 8 -(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 2, 50 mg, 0.14 mmol), (tert-butoxycarbonyl)glycine (30 mg, 0.17 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (69 mg, 0.18 mmol), and diisopropylethylamine (0.07 mL, 0.42 mmol) were dissolved in dichloromethane (0.7 mL), and stirred at room temperature for 12 hours. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (28 mg, 44%).

[0761] Step 2: Preparation of 2-amino-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)acetamide hydrochloride

[0762] Tert-butyl (2-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)carbamate (28 mg, 0.06 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.31 mL), and 4 N hydrochloric acid (0.31 mL) diluted in 1,4-dioxane was added, followed by stirring at 50°C for 16 hours. The resulting solid was filtered and dried to obtain the target compound (16 mg, 68%).

[0763] 1 H NMR (500 MHz, DMSO-d6) δ 11.28 (s, 1H), 8.42-8.28 (m, 4H), 7.01-6.94 (m, 3H), 4.27 (s, 2H), 3.89 (s, 2H), 2.41-2.39 (m, 12H)

[0764]

[0765] [Example 65] Preparation of (S)-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide hydrochloride

[0766]

[0767] N 8-(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 2, 50 mg, 0.14 mmol), (S)-1-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (31 mg, 0.15 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (69 mg, 0.18 mmol), and diisopropylethylamine (0.09 mL, 0.56 mmol) were dissolved in dichloromethane (0.7 mL), and the mixture was stirred at room temperature for 12 h. The reaction was quenched by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, then concentrated under reduced pressure. The residue was purified by column chromatography, dissolved in ethyl acetate, and 4 N hydrochloric acid (0.3 mL) diluted in 1,4-dioxane was added. The mixture was stirred at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (26 mg, 38%).

[0768] 1 H NMR (500 MHz, DMSO-d6) δ 11.57-11.28 (m, 1H), 8.58-8.36 (m, 3H), 7.08-6.99 (m, 3H), 5.21 (s, 1H), 4.27-4.24 (m, 2H), 3.82-3.79 (m, 2H), 2.44-2.41 (m, 12H), 1.30-1.26 (m, 2H)

[0769]

[0770] [Example 66] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-azaspiro[3.3]heptane-2-carboxamide citrate

[0771]

[0772] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 60 mg, 0.18 mmol) and 1,1'-carbonyldiimidazole (58 mg, 0.36 mmol) were dissolved in dichloromethane (2.57 mL) and stirred at room temperature for 1 h. 2-Azaspiro[3.3]heptane (17 mg, 0.18 mmol) and triethylamine (0.07 mL, 0.54 mmol) were added and stirred at room temperature for 6 h. The reaction mixture was purified by column chromatography, dissolved in acetone, and citric acid (34 mg, 0.18 mmol) was added and stirred at room temperature for 1 h. The resulting solid was filtered and dried to obtain the target compound (33 mg, 30%).

[0773] 1 H NMR (500 MHz, DMSO-d6) δ 8.44 (s, 1H), 8.08 (s, 1H), 7.19-7.12 (m, 3H), 6.62 (s, 1H), 5.32-5.23 (m, 1H), 4.28-4.27 (m, 2H), 3.94 (s, 4H), 2.69-2.60 (m, 4H), 2.35-2.30 (m, 12H), 2.17-2.15 (m, 4H), 1.79-1.76 (m, 2H)

[0774]

[0775] [Example 67] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)isoindoline-2-carboxamide

[0776]

[0777] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40 mg, 0.12 mmol) and 1,1'-carbonyldiimidazole (39 mg, 0.24 mmol) were dissolved in dichloromethane (2 mL) and stirred at room temperature for 1 h. Triethylamine (0.05 ml, 0.36 mmol) and isoindole (14 mg, 0.12 mmol) were added and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (11 mg, 21%).

[0778] 1 H NMR (500 MHz, DMSO-d6) δ 10.21 (s, 1H), 8.23 ​​(s, 1H), 8.03 (s, 1H), 7.39-7.38 (m, 4H), 7.17-7.15 (m, 1H), 7.11-7.09 (m, 3H), 4.79 (s, 4H), 4.32-4.31 (m, 2H), 2.36-2.29 (m, 12H)

[0779]

[0780] [Example 68] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide

[0781]

[0782] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40 mg, 0.12 mmol) and 1,1'-carbonyldiimidazole (39 mg, 0.24 mmol) were dissolved in dichloromethane (2 mL) and stirred at room temperature for 1 h. Triethylamine (0.05 ml, 0.36 mmol) and 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine (15 mg, 0.12 mmol) were added and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (10 mg, 19%).

[0783] 1 H NMR (500 MHz, DMSO-d6) δ 8.63-8.62 (m, 2H), 8.52-8.51 (m, 2H), 7.46-7.45 (m, 1H), 7.17-7.09 (m, 5H), 4.84-4.82 (m, 4H), 4.32-4.31 (m, 2H), 2.37-2.36 (m, 12H)

[0784]

[0785] [Example 69] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-oxoazetidine-1-carboxamide citrate

[0786]

[0787] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 60 mg, 0.18 mmol) and 1,1'-carbonyldiimidazole (58 mg, 0.36 mmol) were dissolved in dichloromethane (0.9 mL) and stirred at room temperature for 1 h. Azetidine-3-one hydrochloride (19 mg, 0.18 mmol) and triethylamine (0.07 mL, 0.54 mmol) were added and stirred at room temperature for 6 h. The reaction mixture was purified by column chromatography, dissolved in acetone, and citric acid (34 mg, 0.18 mmol) was added and stirred at room temperature for 1 h. The resulting solid was filtered and dried to obtain the target compound (30 mg, 43%).

[0788] 1 H NMR (500 MHz, DMSO-d6) δ 8.93 (s, 1H), 8.11 (s, 1H), 7.19-7.10 (m, 4H), 6.66-6.49 (m, 1H), 4.82 (s, 4H), 4.30-4.29 (m, 2H), 2.70-2.64 (m, 4H), 2.35-2.31 (m, 12H)

[0789]

[0790] [Example 70] Preparation of ((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)carbamoyl)glycine hydrochloride

[0791]

[0792] Step 1: Preparation of methyl((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)glycinate

[0793] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 100 mg, 0.30 mmol) and 1,1'-carbonyldiimidazole (98 mg, 0.61 mmol) were dissolved in dichloromethane (1.5 mL) and stirred at room temperature for 1 h. Methyl glycinate (27 mg, 0.30 mmol) and triethylamine (0.13 mL, 0.91 mmol) were added and stirred at room temperature for 12 h. The reaction was quenched by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (32 mg, 26%).

[0794] Step 2: Preparation of ((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)carbamoyl)glycine hydrochloride

[0795] Methyl((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)glycinate (32 mg, 0.079 mmol) prepared in Step 1 above was dissolved in tetrahydrofuran (0.5 mL), methanol (0.5 mL), and distilled water (0.5 mL), then potassium hydroxide (22 mg, 0.40 mmol) was added and stirred at room temperature for 12 hours. The reaction mixture was acidified with a 4 N hydrochloric acid aqueous solution, and the resulting solid was filtered and dried to obtain the target compound (16 mg, 46%).

[0796] 1 H NMR (500 MHz, DMSO-d6) δ 12.69-12.51 (brs, 1H), 8.67 (s, 1H), 7.96 (s, 1H), 7.21-7.09 (m, 3H), 6.41-6.40 (m, 1H), 6.09 (s, 1H), 4.31-4.30 (m, 2H), 3.80-3.79 (m, 2H), 2.35-2.27 (m, 12H)

[0797]

[0798] [Example 71] Preparation of 3-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)propionic acid citrate

[0799]

[0800] Step 1: Preparation of methyl 3-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)ureido)propanoate

[0801] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 60 mg, 0.18 mmol) and 1,1'-carbonyldiimidazole (58 mg, 0.36 mmol) were dissolved in dichloromethane (2.5 mL) and stirred at room temperature for 1 h. Methyl 3-aminopropanoate (18 mg, 0.18 mmol) and triethylamine (0.07 mL, 0.54 mmol) were added and stirred at room temperature for 6 h. The reaction mixture was purified by column chromatography to obtain the target compound (18 mg, 26%).

[0802] Step 2: Preparation of 3-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)propionic acid citrate

[0803] Methyl 3-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)ureido)propanoate (30 mg, 0.07 mmol) was dissolved in tetrahydrofuran (0.3 mL), methanol (0.3 mL), and distilled water (0.3 mL), potassium hydroxide (19 mg, 0.35 mmol) was added, and the mixture was stirred at room temperature for 12 h. The solvent was removed, and the resulting solid was filtered and dried using dichloromethane to obtain the target compound (16 mg, 55%). After this, the mixture was dissolved in acetone, citric acid (7 mg, 0.04 mmol) was added, and the mixture was stirred at room temperature for 12 h. The resulting solid was filtered and dried to obtain the citrate salt of the target compound.

[0804] 1 H NMR (500 MHz, DMSO-d6) δ 12.31-12.03 (brs, 1H), 7.95-7.94 (m, 1H), 7.15-7.04 (m, 4H), 6.67-6.45 (m, 1H), 6.08-6.04 (m, 1H), 4.88-4.87 (m, 1H), 4.29-4.28 (m, 2H), 2.46-2.40 (m, 4H), 2.37-2.34 (m, 12H)

[0805]

[0806] [Example 72] Preparation of 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,3,5-triazepane-2,4-dione

[0807]

[0808] 1-(2-Aminoethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea hydrochloride (Example 99, 40 mg, 0.10 mmol) and 1,1'-carbonyldiimidazole (31 mg, 0.19 mmol) were dissolved in dichloromethane (2 mL) and stirred at room temperature for 1 h. Triethylamine (0.04 ml, 0.29 mmol) and 40% methylamine solution (7 mg, 0.24 mmol) were added and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (11 mg, 28%).

[0809] 1 H NMR (500 MHz, DMSO-d6) δ 10.31-10.21 (brs, 1H), 8.04-8.02 (m, 1H), 7.90 (s, 1H), 7.21-7.05 (m, 5H), 4.35-4.34 (m, 2H), 3.88-3.85 (m, 2H), 3.38-3.37 (m, 2H), 2.30-2.29 (m, 12H)

[0810]

[0811] [Example 73] Preparation of N-(2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)ethyl)acetamide

[0812]

[0813] 1-(2-Aminoethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea hydrochloride (Example 99, 40 mg, 0.10 mmol) and triethylamine (0.03 ml, 0.19 mmol) were dissolved in dimethylformamide (2 mL). Acetic anhydride (0.01 ml, 0.14 mmol) was added and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (13 mg, 32%).

[0814] 1 H NMR (500 MHz, DMSO-d6) δ 8.45 (s, 1H), 7.97-7.94 (m, 2H), 7.20-7.03 (m, 5H), 6.21-6.11 (m, 1H), 4.29 (s, 2H), 3.28-3.27 (m, 4H), 2.36-2.35 (m, 12H), 1.98 (s, 3H)

[0815]

[0816] [Example 74] Preparation of 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-((tetrohydrofuran-3-yl)methyl)urea hydrochloride

[0817]

[0818] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 60 mg, 0.18 mmol) and 1,1'-carbonyldiimidazole (58 mg, 0.36 mmol) were dissolved in dichloromethane (2.5 mL) and stirred at room temperature for 1 h. (Tetrahydrofuran-3-yl)methanamine (18 mg, 0.18 mmol) and triethylamine (0.07 mL, 0.54 mmol) were added and stirred at room temperature for 6 h. The reaction was quenched by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography, dissolved in ethyl acetate, and 4 N hydrochloric acid (0.3 mL) diluted in 1,4-dioxane was added, followed by stirring at room temperature for 6 hours. The resulting solid was filtered and dried to obtain the target compound (14 mg, 18%).

[0819] 1H NMR (500 MHz, DMSO-d6) δ 13.48 (s, 1H), 8.83 (s, 1H), 8.17 (s, 1H), 7.18-7.11 (m, 3H), 6.59-6.49 (m, 2H), 4.30-4.29 (m, 2H), 3.76-3.74 (m, 3H), 3.44-3.41 (m, 1H), 3.13-3.10 (m, 2H), 2.38-2.34 (m, 12H), 1.99-1.95 (m, 1H)

[0820]

[0821] [Example 75] Preparation of (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methylazetidine-2-carboxamide hydrochloride

[0822]

[0823] Step 1: Preparation of tert-butyl (R)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)-2-methylazetidine-1-carboxylate

[0824] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol), (2R)-1-[(tert-butoxy)carbonyl]-2-methylazetidine-2-carboxylic acid (36 mg, 0.17 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (75 mg, 0.20 mmol), and diisopropylethylamine (0.11 mL, 0.61 mmol) were dissolved in dichloromethane (0.7 ml), and stirred at room temperature for 5 hours. The reaction was quenched by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, then concentrated under reduced pressure. The residue was purified by column chromatography, dissolved in ethyl acetate, and hexane was added to precipitate a solid to obtain the target compound (27 mg, 37%).

[0825] Step 2: Preparation of (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methylazetidine-2-carboxamide hydrochloride

[0826] Tert-butyl (R)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)-2-methylazetidine-1-carboxylate (27 mg, 0.056 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.28 mL), and 2 M hydrochloric acid (0.11 mL) diluted in diethyl ether was added, followed by stirring at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (19 mg, 78%).

[0827] 1 H NMR (500 MHz, DMSO-d6) δ 14.09 (s, 1H), 11.26 (s, 1H), 9.68 (s, 1H), 9.13 (s, 1H), 8.50 (s, 1H), 7.30-7.13 (m, 4H), 6.53 (s, 1H), 4.31 (s, 2H), 4.00-3.71 (m, 2H), 2.88-2.86 (m, 1H), 2.36-2.34 (m, 12H), 1.99 (s, 3H)

[0828]

[0829] [Example 76] Preparation of (R)-2-(azetidin-2-yl)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)acetamide hydrochloride

[0830]

[0831] Step 1: Preparation of tert-butyl (R)-2-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)azetidine-1-carboxylate

[0832] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol), (R)-2-(1-(tert-butoxycarbonyl)azetidin-2-yl)acetic acid (36 mg, 0.17 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (75 mg, 0.20 mmol), and diisopropylethylamine (0.11 mL, 0.61 mmol) were dissolved in dichloromethane (0.7 ml), and the mixture was stirred at room temperature for 12 h. The reaction was quenched by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, then concentrated under reduced pressure. The residue was purified by column chromatography, dissolved in ethyl acetate, and hexane was added to precipitate a solid to obtain the target compound (20 mg, 27%).

[0833] Step 2: Preparation of (R)-2-(azetidin-2-yl)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)acetamide hydrochloride

[0834] Tert-butyl (R)-2-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)azetidine-1-carboxylate (20 mg, 0.041 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.21 mL), and 2 M hydrochloric acid (0.08 mL) diluted in diethyl ether was added, followed by stirring at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (14 mg, 81%).

[0835] 1H NMR (500 MHz, DMSO-d6) δ 13.81 (s, 1H), 10.89-10.84 (m, 1H), 8.97-8.96 (m, 1H), 8.54-8.47 (m, 1H), 8.19 (s, 1H), 7.22-7.13 (m, 4H), 4.30 (s, 2H), 3.83-3.80 (m, 2H), 3.23-3.20 (m, 2H), 2.89-2.87 (m, 2H), 2.36-2.33 (m, 12H)

[0836]

[0837] [Example 77] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-phenylazetidine-1-carboxamide citrate

[0838]

[0839] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 60 mg, 0.18 mmol) and 1,1'-carbonyldiimidazole (58 mg, 0.36 mmol) were dissolved in dichloromethane (0.9 mL) and stirred at room temperature for 1 h. 3-Phenylazetidine (24 mg, 0.18 mmol) and triethylamine (0.07 mL, 0.54 mmol) were added and stirred at room temperature for 6 h. The reaction mixture was purified by column chromatography, dissolved in acetone, and citric acid (34 mg, 0.18 mmol) was added and stirred at room temperature for 3 h. The resulting solid was filtered and dried to obtain the target compound (29 mg, 25%).

[0840] 1H NMR (500 MHz, DMSO-d6) δ 8.59 (s, 1H), 8.12 (s, 1H), 7.41-7.37 (m, 4H), 7.30-7.26 (m, 1H), 7.19-7.11 (m, 3H), 6.64 (s, 1H), 4.43-4.39 (m, 2H), 4.29-4.28 (m, 2H), 3.99-3.98 (m, 2H), 3.88-3.87 (m, 1H), 2.69-2.66 (m, 4H), 2.35-2.31 (m, 12H)

[0841]

[0842] [Example 78] Preparation of (S)-1-(2,3-dihydro-1H-inden-1-yl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)urea hydrochloride

[0843]

[0844] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 60 mg, 0.18 mmol) and 1,1'-carbonyldiimidazole (58 mg, 0.36 mmol) were dissolved in dichloromethane (2.57 mL) and stirred at room temperature for 1 h. (S)-2,3-dihydro-1H-inden-1-amine (23 mg, 0.18 mmol) and triethylamine (0.07 mL, 0.54 mmol) were added and stirred at room temperature for 6 h. The reaction mixture was purified by column chromatography, dissolved in ethyl acetate, and 2 M hydrochloric acid diluted in diethyl ether (0.36 mL) was added and stirred at room temperature for 6 h. The resulting solid was filtered and dried to obtain the target compound (16 mg, 22%).

[0845] 1H NMR (500 MHz, DMSO-d6) δ 13.50 (s, 1H), 8.92 (s, 1H), 8.30 (s, 1H), 7.30-7.12 (m, 7H), 6.88 (s, 1H), 6.65-6.64 (m, 1H), 5.22-5.21 (m, 1H), 4.31-4.30 (m, 2H), 2.98-2.92 (m, 2H), 2.45-2.44 (m, 12H), 1.99 (s, 1H)

[0846]

[0847] [Example 79] Preparation of (S)-N2-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-N1-methylazetidine-1,2-dicarboxamide

[0848]

[0849] (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide (Example 65, 40 mg, 0.12 mmol) and 1,1'-carbonyldiimidazole (31 mg, 0.19 mmol) were dissolved in dichloromethane (2 mL) and stirred at room temperature for 1 h. Triethylamine (0.04 ml, 0.29 mmol) and 40% methylamine solution (8 mg, 0.24 mmol) were added and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (12 mg, 28%).

[0850] 1 H NMR (500 MHz, DMSO-d6) δ 8.01-7.95 (m, 1H), 7.18-7.14 (m, 4H), 4.61-4.58 (m, 1H), 4.32-4.28 (m, 2H), 3.95-3.92 (m, 1H), 3.18-3.16 (m, 1H), 2.66 (s, 3H), 2.35 (s, 6H), 2.31 (s, 3H), 2.28 (s, 3H), 2.16-2.13 (m, 2H)

[0851]

[0852] [Example 80] Preparation of (R)-1-(2,3-dihydro-1H-inden-1-yl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)urea hydrochloride

[0853]

[0854] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 60 mg, 0.18 mmol) and 1,1'-carbonyldiimidazole (58 mg, 0.36 mmol) were dissolved in dichloromethane (0.9 mL) and stirred at room temperature for 1 h. (R)-2,3-dihydro-1H-inden-1-amine (23 mg, 0.18 mmol) and triethylamine (0.07 mL, 0.54 mmol) were added and stirred at room temperature for 6 h. The reaction mixture was purified by column chromatography, dissolved in ethyl acetate, and 2 M hydrochloric acid diluted in diethyl ether (0.36 mL) was added and stirred at room temperature for 10 h. The resulting solid was filtered and dried to obtain the target compound (10 mg, 3%).

[0855] 1 H NMR (500 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.37 (s, 1H), 7.30-7.28 (m, 2H), 7.26-7.23 (m, 4H), 7.23-7.21 (m, 2H), 6.94-6.92 (d, 1H), 6.77 (s, 1H), 6.19 (s, 1H), 5.23-5.20 (m, 1H), 4.32-4.31 (d, 2H), 2.41-2.37 (m, 12H)

[0856]

[0857] [Example 81] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(2-oxoazetidin-1-yl)acetamide

[0858]

[0859] 2-Amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide (Example 10, 50 mg, 0.13 mmol) and triethylamine (0.05 ml, 0.39 mmol) were dissolved in tetrahydrofuran (2 ml). 3-Bromopropionyl chloride (24 mg, 0.14 mmol) was added and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (17 mg, 32%).

[0860] 1 H NMR (500 MHz, DMSO-d6) δ 10.02 (s, 1H), 8.51 (s, 1H), 8.19 (s, 1H), 7.17-7.15 (m, 1H), 7.14-7.08 (m, 2H), 6.38-6.36 (m, 1H), 6.35-6.33 (m, 1H), 6.15-6.12 (d, 1H), 5.66-5.64 (d, 1H), 4.31-4.30 (d, 1H), 4.01-4.00 (d, 1H), 2.35 (s, 6H), 2.29 (s, 3H), 2.22 (s, 3H)

[0861]

[0862] [Example 82] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-4-phenylpiperidine-1-carboxamide

[0863]

[0864] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40 mg, 0.12 mmol) and 1,1'-carbonyldiimidazole (39 mg, 0.24 mmol) were dissolved in dichloromethane (2 mL) and stirred at room temperature for 1 h. Triethylamine (0.05 ml, 0.36 mmol) and 4-methylpiperidine (19 mg, 0.12 mmol) were added and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (12 mg, 21%).

[0865] 1 H NMR (500 MHz, DMSO-d6) δ 8.39 (s, 1H), 7.96 (s, 1H), 7.32-7.29 (m, 5H), 7.27-7.10 (m, 4H), 6.46 (s, 1H), 4.81 (s, 1H), 4.33-4.29 (m, 4H), 2.93-2.88 (t, 1H), 2.77-2.75 (m, 1H), 2.35 (s, 6H), 2.28(s, 3H), 2.22 (s, 3H), 1.84-1.82 (d, 2H), 1.61-1.59 (m, 2H)

[0866]

[0867] [Example 83] Preparation of N-(8-((2,6-dimethylbenzyl l) amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-phenylpiperidine-1-carboxamide

[0868]

[0869] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40 mg, 0.12 mmol) and 1,1'-carbonyldiimidazole (39 mg, 0.24 mmol) were dissolved in dichloromethane (2 mL) and stirred at room temperature for 1 h. Triethylamine (0.05 ml, 0.36 mmol) and 3-phenylpyrrolidine (18 mg, 0.12 mmol) were added and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (28 mg, 48%).

[0870] 1 H NMR (500 MHz, DMSO-d6) δ 8.37 (s, 1H), 7.95 (s, 1H), 7.35-7.33 (m, 5H), 7.26-7.25 (m, 1H), 7.15-7.14 (m, 1H), 7.10-7.08 (m, 2H), 6.43 (s, 1H), 4.78 (s, 1H), 4.27-4.23 (m, 4H), 2.93-2.84 (m, 2H), 2.71-2.69 (m, 1H), 2.34 (s, 6H), 2.27(s, 3H), 2.20 (s, 3H), 1.94-1.93 (m, 2H), 1.77-1.74 (m, 2H), 1.70-1.68 (m, 1H)

[0871]

[0872] [Example 84] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-phenylpyrrolidine-1-carboxamide

[0873]

[0874] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 40 mg, 0.12 mmol) and 1,1'-carbonyldiimidazole (39 mg, 0.24 mmol) were dissolved in dichloromethane (2 mL) and stirred at room temperature for 1 h. Triethylamine (0.05 ml, 0.36 mmol) and 3-phenylpyrrolidine (18 mg, 0.12 mmol) were added and stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography to obtain the target compound (4 mg, 7%).

[0875] 1 H NMR (500 MHz, DMSO-d6) δ 8.05-7.99 (m, 2H), 7.36-7.35 (m, 5H), 7.27-7.26 (m, 1H), 7.17-7.16 (m, 1H), 7.10-7.09 (m, 2H), 6.48 (s, 1H), 4.78 (s, 1H), 4.29-4.28 (m, 2H), 3.93-3.89 (t, 1H), 3.67-3.65 (m, 1H), 3.47-3.45 (m, 2H), 2.35 (s, 6H), 2.28, (s, 3H), 2.20 (s, 3H), 1.48-146 (m, 2H)

[0876]

[0877] [Example 85] Preparation of (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-2-carboxamide hydrochloride

[0878]

[0879] Step 1: Preparation of di-tert-butyl (R)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)piperazine-1,4-dicarboxylate

[0880] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol), (R)-1,4-bis(tert-butoxycarbonyl)piperazine-2-carboxylic acid (55 mg, 0.17 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (75 mg, 0.20 mmol), and diisopropylethylamine (0.11 mL, 0.61 mmol) were dissolved in dichloromethane (0.7 mL), and stirred at room temperature for 12 h. The reaction was quenched by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, then concentrated under reduced pressure. The residue was purified by column chromatography to obtain the target compound (91 mg, 99%).

[0881] Step 2: Preparation of (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-2-carboxamide hydrochloride

[0882] Di-tert-butyl (R)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)piperazine-1,4-dicarboxylate (91 mg, 0.15 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.7 ml), and 2 M hydrochloric acid (0.30 mL) diluted in diethyl ether was added, followed by stirring at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (63 mg, 95%).

[0883] 1H NMR (500 MHz, DMSO-d6) δ 8.44 (s, 1H), 7.22-7.21 (m, 1H), 7.16-7.15 (m, 3H), 6.46 (s, 1H), 4.32-4.31 (m, 2H), 2.69 (s, 2H), 2.46-2.43 (m, 6H), 2.40-2.37 (m, 6H), 2.01-1.99 (m, 2H), 1.48-1.46 (m, 2H)

[0884]

[0885] [Example 86] Preparation of N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxyacetamide citrate

[0886]

[0887] Step 1: Preparation of 2-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-2-oxoethylacetate

[0888] N 8 -(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (Intermediate 2, 80 mg, 0.22 mmol) and triethylamine (0.092 mL, 0.66 mmol) were dissolved in dichloromethane (3.14 mL), and the mixture was stirred at room temperature for 10 minutes. 2-Chloro-2-oxoethyl acetate (0.032 mL, 0.29 mmol) was slowly added dropwise, and the mixture was stirred at room temperature for 12 hours. The reaction mixture was purified by column chromatography to obtain the target compound (18 mg, 20%).

[0889] Step 2: Preparation of N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxyacetamide citrate

[0890] 2-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl acetate (50 mg, 0.12 mmol) prepared in Step 1 above was dissolved in tetrahydrofuran (1 mL), methanol (1 mL), and distilled water (1 mL), potassium hydroxide (33 mg, 0.60 mmol) was added, and the mixture was stirred at room temperature for 12 hours. The reaction was quenched by adding distilled water, extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (20 mg, 45%). After this, the mixture was dissolved in acetone, citric acid (10 mg, 0.05 mmol) was added, and the mixture was stirred at room temperature for 12 hours. The resulting solid was filtered and dried to obtain the citrate salt of the target compound.

[0891] 1 H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 8.33 (s, 1H), 6.98-6.96 (d, 2H), 6.74-6.67 (m, 1H), 5.80-5.77 (m, 1H), 5.33-5.31 (m, 1H), 4.28-4.27 (d, 2H), 4.03-4.03 (d, 2H), 2.71-2.59 (m, 6H), 2.36-2.26 (m, 12H)

[0892]

[0893] [Example 87] Preparation of 1-(2-aminoethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-methylurea hydrochloride

[0894]

[0895] Step 1: Preparation of tert-butyl (2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)ethyl)carbamate

[0896] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 60.0 mg, 0.18 mmol) was dissolved in dichloromethane. 1,1'-Carbonyldiimidazole (58.0 mg, 0.36 mmol), triethylamine (0.07 mL, 0.54 mmol), and tert-butyl (2-(methylamino)ethyl)carbamate (30.0 mg, 0.18 mmol) were added and stirred at room temperature for 16 h. When the reaction was complete, dichloromethane (50 mL) and distilled water (50 mL) were added, the layers were separated, and the organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the target compound (22 mg, 23%).

[0897] Step 2: Preparation of 1-(2-aminoethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-methylurea hydrochloride

[0898] Tert-butyl (2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)ethyl)carbamate (15.0 mg, 0.03 mmol) prepared in Step 1 above was dissolved in ethyl acetate. 4 N hydrochloric acid (0.6 mL, 0.5 M) dissolved in 1,4-dioxane was added and stirred at room temperature for 12 h. After the reaction was completed, filtration was performed to obtain the target compound (12 mg, 78%).

[0899] 1 H NMR (500 MHz, DMSO-d6) δ 8.83 (s, 1H), 8.39 (s, 1H), 8.01 (s, 3H), 7.41 (s, 1H), 7.21-7.14 (m, 3H), 6.26 (s, 1H), 4.31-4.30 (d, 2H), 3.63-3.61 (t, 1H), 3.07 (s, 3H), 3.03-3.02 (m, 2H), 2.39-2.37 (m, 12H)

[0900]

[0901] [Example 88] Preparation of 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-(2-hydroxyethyl)urea citrate

[0902]

[0903] Step 1: Preparation of 2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)ureido)ethyl acetate

[0904] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 80 mg, 0.24 mmol) and 1,1'-carbonyldiimidazole (77 mg, 0.48 mmol) were dissolved in dichloromethane (3.4 mL) and stirred at room temperature for 1 h. 2-Aminoethyl acetate hydrochloride (33 mg, 0.24 mmol) and triethylamine (0.1 mL, 0.72 mmol) were added and stirred at room temperature for 6 h. The reaction mixture was purified by column chromatography to obtain the target compound (33 mg, 30%).

[0905] Step 2: Preparation of 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-(2-hydroxyethyl)urea citrate

[0906] 2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)ureido)ethyl acetate (100 mg, 0.23 mmol) prepared in Step 1 above was dissolved in tetrahydrofuran (1.15 mL), methanol (1.15 mL), and distilled water (1.15 mL), potassium hydroxide (66 mg, 1.18 mmol) was added, and the mixture was stirred at room temperature for 12 hours. The solvent was removed, distilled water was added, and the reaction was quenched, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the target compound (70 mg, 80%) was obtained. This was dissolved in acetone, citric acid (35 mg, 0.18 mmol) was added, and the mixture was stirred at room temperature for 12 hours. The resulting solid was filtered and dried to obtain the citrate salt of the target compound.

[0907] 1 H NMR (500 MHz, DMSO-d6) δ 8.06 (s, 1H), 7.21-7.11 (m, 3H), 6.28 (s, 1H), 4.77-4.75 (m, 1H), 4.31-4.30 (d, 2H), 3.47-3.46 (m, 2H), 3.18-3.17 (m, 2H), 2.69-2.64 (m, 4H), 2.36-2.26 (m, 12H), 2.01-2.00 (m, 2H)

[0908]

[0909] [Example 89] Preparation of (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)pyrrolidine-3-carboxamide hydrochloride

[0910]

[0911] Step 1: Preparation of tert-butyl (R)-3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)pyrrolidine-1-carboxylate

[0912] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol), (R)-1-bak-3-pyrrolidinecarboxylic acid (36 mg, 0.17 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (75 mg, 0.20 mmol), and diisopropylethylamine (0.11 mL, 0.61 mmol) were dissolved in dichloromethane (0.7 ml) and stirred at room temperature for 12 hours. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (73 mg, 99%).

[0913] Step 2: Preparation of (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)pyrrolidine-3-carboxamide hydrochloride

[0914] Tert-butyl (R)-3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)pyrrolidine-1-carboxylate (73 mg, 0.15 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.7 ml), and 2 M hydrochloric acid (0.30 mL) diluted in diethyl ether was added, followed by stirring at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (55 mg, 85%).

[0915] 1 H NMR (500 MHz, DMSO-d6) δ 14.06 (s, 1H), 11.09 (s, 1H), 9.43-9.27 (m, 2H), 8.52 (sm 1H), 7.22-7.13 (m, 4H), 6.51 (s, 1H), 4.31-4.3- (d, 1H), 3.28-3.27 (m, 2H), 2.40-2.37 (m, 12H), 2.11-2.08 (m, 2H)

[0916]

[0917] [Example 90] Preparation of (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-2-carboxamide hydrochloride

[0918]

[0919] Step 1: Preparation of tert-butyl (R)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)piperidine-1-carboxylate

[0920] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol), (R)-(+)-N-bak-2-piperidinecarboxylic acid (38 mg, 0.17 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (75 mg, 0.20 mmol), and diisopropylethylamine (0.11 mL, 0.61 mmol) were dissolved in dichloromethane (0.7 ml) and stirred at room temperature for 12 hours. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (75 mg, 98%).

[0921] Step 2: Preparation of (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-2-carboxamide hydrochloride

[0922] Tert-butyl (R)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)piperidine-1-carboxylate (75 mg, 0.15 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.7 ml), and 2 M hydrochloric acid (0.30 mL) diluted in diethyl ether was added, followed by stirring at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (55 mg, 83%).

[0923] 1 H NMR (500 MHz, DMSO-d6) δ 13.86 (s, 1H), 11.28 (s, 1H), 9.31-9.29 (m, 1H), 8.89-8.87 (m, 1H), 8.44 (s, 1H), 7.23-7.16 (m, 4H), 6.44 (s, 1H), 4.31-4.30 (d, 2H), 4.05-4.01 (m, 1H), 3.06-3.02 (m, 2H), 2.42-2.37 (m, 14H), 2.01-2.00 (m, 2H), 1.88-1.76 (m, 2H), 1.69-1.59 (m, 4H), 1.47-1.45 (m, 2H)

[0924]

[0925] [Example 91] Preparation of (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(pyrrolidin-2-yl)acetamide hydrochloride

[0926]

[0927] Step 1: Preparation of tert-butyl (R)-2-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)pyrrolidine-1-carboxylate

[0928] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol), (R)-2-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)acetic acid (38 mg, 0.17 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (75 mg, 0.20 mmol), and diisopropylethylamine (0.11 mL, 0.61 mmol) were dissolved in dichloromethane (0.7 ml), and the mixture was stirred at room temperature for 12 h. The reaction was terminated by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, then concentrated under reduced pressure. The residue was purified by column chromatography to obtain the target compound (76 mg, 99%).

[0929] Step 2: Preparation of (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(pyrrolidin-2-yl)acetamide hydrochloride

[0930] Tert-butyl (R)-2-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)pyrrolidine-1-carboxylate (76 mg, 0.15 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.7 ml), and 2 M hydrochloric acid (0.30 mL) diluted in diethyl ether was added, followed by stirring at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (54 mg, 82%).

[0931] 1H NMR (500 MHz, DMSO-d6) δ 14.12 (s, 1H), 11.01 (s, 1H), 9.30-9.20 (m, 2H), 8.52 (s, 1H), 7.21-7.07 (m, 4H), 6.55 (s, 1H), 4.31 (s, 1H), 3.82-3.80 (m, 1H), 3.19-3.18 (m, 2H), 3.03-2.99 (m, 2H), 2.40-2.37 (m, 12H), 2.18-2.17 (m, 1H), 1.99-1.87 (m, 2H), 1.66-1.64 (m, 1H)

[0932]

[0933] [Example 92] Preparation of N8-(2,6-dimethylbenzyl)-N6-isopropyl-2,3-dimethylimadazo[1,2-a]pyridine-6,8-diamine

[0934]

[0935] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol), acetone (0.016 mL, 0.22 mmol), and acetic acid (0.012 mL, 0.22 mmol) were dissolved in tetrahydrofuran (2.16 mL), and the mixture was stirred at room temperature for 2 hours. Sodium triacetoxyborohydride (46 mg, 0.22 mmol) was slowly added, and the mixture was stirred at room temperature for 12 hours. The reaction was quenched by adding aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the target compound (8 mg, 16%) was obtained.

[0936] 1H NMR (500 MHz, DMSO-d6) δ 8.47-8.45 (d, 1H), 7.15-7.13 (m, 2H), 7.10-7.09 (m, 2H), 6.65 (s, 1H), 5.50-5.49 (m, 1H), 4.48-4.47 (d, 2H), 2.76 (s, 3H), 2.55 (s, 3H), 2.27-2.01 (m, 12H), 2.00-1.98 (m, 1H)

[0937]

[0938] [Example 93] Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(pyrrolidin-2-yl)acetamide hydrochloride

[0939]

[0940] Step 1: Preparation of tert-butyl (S)-2-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)pyrrolidine-1-carboxylate

[0941] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol), (S)-2-(1-bak-2-pyrrolidinyl)acetic acid (38 mg, 0.17 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (75 mg, 0.20 mmol), and diisopropylethylamine (0.11 mL, 0.61 mmol) were dissolved in dichloromethane (0.7 ml) and stirred at room temperature for 12 hours. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (75 mg, 98%).

[0942] Step 2: Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(pyrrolidin-2-yl)acetamide hydrochloride

[0943] Tert-butyl (S)-2-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)pyrrolidine-1-carboxylate (75 mg, 0.15 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.7 ml), and 2 M hydrochloric acid (0.30 mL) diluted in diethyl ether was added, followed by stirring at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (52 mg, 79%).

[0944] 1 H NMR (500 MHz, DMSO-d6) δ 13.90 (s, 1H), 10.90 (s, 1H), 9.20-9.03 (m, 2H), 8.50 (s, 1H), 7.23-7.21 (m, 1H), 7.15-7.14 (m, 2H), 7.00 (s, 1H), 4.31-4.30 (d, 2H), 3.83-3.80 (m, 2H), 2.40-2.37 (m, 12H), 2.18-2.16 (m, 1H), 1.99-90 (m, 2H), 1.66-1.63 (m, 1H)

[0945]

[0946] [Example 94] Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-2-carboxamide hydrochloride

[0947]

[0948] Step 1: Preparation of di-tert-butyl (S)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)piperazine-1,4-dicarboxylate

[0949] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol), (S)-1,4-bis(tert-butoxycarbonyl)piperazine-2-carboxylic acid (55 mg, 0.17 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (75 mg, 0.20 mmol), and diisopropylethylamine (0.11 mL, 0.61 mmol) were dissolved in dichloromethane (0.7 ml), and stirred at room temperature for 12 h. The reaction was quenched by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, then concentrated under reduced pressure. The residue was purified by column chromatography to obtain the target compound (91 mg, 99%).

[0950] Step 2: Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-2-carboxamide hydrochloride

[0951] Di-tert-butyl (S)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)piperazine-1,4-dicarboxylate (91 mg, 0.15 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.7 ml), and 2 M hydrochloric acid (0.30 mL) diluted in diethyl ether was added, followed by stirring at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (61 mg, 92%).

[0952] 1 H NMR (500 MHz, DMSO-d6) δ 8.44 (s, 1H), 7.23-7.14 (m, 4H), 6.46 (s, 1H), 4.45-4.42 (m, 1H), 4.32-4.31 (d, 2H), 2.69 (s, 3H), 2.43-2.42 (m, 12H), 2.01-1.99 (m, 2H), 1.48-14.6 (m, 2H)

[0953]

[0954] [Example 95] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(2-hydroxyacetamido)acetamide

[0955]

[0956] 2-Amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide (Example 10, 40 mg, 0.12 mmol) was dissolved in tetrahydrofuran (1 ml), methanol (1 ml), and distilled water (1 ml). Potassium hydroxide (11 mg, 0.19 mmol) was added, and the mixture was stirred at room temperature for 12 hours. The reaction was terminated by adding 1 N aqueous hydrochloric acid solution, and the pH of the mixture was maintained at 2. After extraction with ethyl acetate, the organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The concentrated residue was dried to obtain the target compound (9 mg, 58%).

[0957] 1 H NMR (500 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.16 (s, 1H), 8.03-8.01 (m, 1H), 7.17-7.14 (m, 1H), 7.12-7.09 (m, 3H), 6.26 (s, 1H), 5.01 (s, 1H), 4.31-4.30 (d, 2H), 3.97-3.96 (d, 2H), 3.79 (s, 2H), 2.35 (s, 6H), 2.28-2.21 (m, 6H)

[0958]

[0959] [Example 96] Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide citrate

[0960]

[0961] Step 1: Preparation of (S)-1-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl acetate

[0962] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 80 mg, 0.24 mmol), (S)-2-acetoxypropionic acid (35 mg, 0.26 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (118 mg, 0.31 mmol), and diisopropylethylamine (0.12 mL, 0.72 mmol) were dissolved in dichloromethane (3.42 mL) and stirred at room temperature for 11 hours. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (39 mg, 40%).

[0963] Step 2: Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide citrate

[0964] (S)-1-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl acetate (39 mg, 0.09 mmol) prepared in Step 1 above was dissolved in tetrahydrofuran (0.45 mL), methanol (0.45 mL), and distilled water (0.45 mL), potassium hydroxide (26 mg, 0.47 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The solvent was removed, distilled water was added, and the reaction was quenched, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the target compound (20 mg, 61%) was obtained. This was dissolved in acetone, citric acid (10 mg, 0.054 mmol) was added, and the mixture was stirred at room temperature for 12 hours. The resulting solid was filtered and dried to obtain the citrate salt of the target compound.

[0965] 1 H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 8.38 (s, 1H), 7.21-7.19 (m, 1H), 7.17-7.16 (m, 2H), 6.80-6.67 (m, 1H), 5.87-5.86 (m, 1H), 5.34-5.32 (m, 1H), 4.31-4.30 (d, 2H), 4.20-4.19 (m, 1H), 2.71-2.58 (m, 4H), 2.35-2.26 (m, 12H), 1.35-1.33 (d, 3H)

[0966]

[0967] [Example 97] Preparation of (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide citrate

[0968]

[0969] Step 1: Preparation of (R)-1-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl acetate

[0970] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 80 mg, 0.24 mmol), (R)-2-acetoxypropionic acid (35 mg, 0.26 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (118 mg, 0.31 mmol), and diisopropylethylamine (0.12 mL, 0.72 mmol) were dissolved in dichloromethane (3.42 mL) and stirred at room temperature for 16 hours. Distilled water was added to quench the reaction, and extraction was performed with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (40 mg, 40%).

[0971] Step 2: Preparation of (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide citrate

[0972] (R)-1-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl acetate (40 mg, 0.09 mmol) prepared in the above step 1 was dissolved in tetrahydrofuran (0.9 mL), methanol (0.9 mL), and distilled water (0.9 mL), potassium hydroxide (26 mg, 0.47 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The solvent was removed, distilled water was added, and the reaction was quenched, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, dissolved in dichloromethane, and diethyl ether was added to precipitate a solid to obtain the target compound (20 mg, 60%). After this, it was dissolved in acetone, citric acid (10 mg, 0.054 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The resulting solid was filtered and dried to obtain the citrate salt of the target compound.

[0973] 1 H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 8.39 (s, 1H), 7.21-7.12 (m, 3H), 6.81-6.74 (m, 1H), 5.87-5.86 (d, 2H), 4.20-4.19 (m, 1H), 2.71-2.62 (m, 4H), 2.35-2.27 (m, 12H), 2.09-2.07 (m, 2H), 1.35-1.33 (d, 3H)

[0974]

[0975] [Example 98] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(methylamino)acetamide hydrochloride

[0976]

[0977] Step 1: Preparation of tert-butyl (2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)(methyl)carbamate

[0978] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol), N-(tert-butoxycarbonyl)-N-methylglycine (31 mg, 0.17 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (75 mg, 0.20 mmol), and diisopropylethylamine (0.11 mL, 0.61 mmol) were dissolved in dichloromethane (0.7 ml) and stirred at room temperature for 12 hours. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (70 mg, 99%).

[0979] Step 2: Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(methylamino)acetamide hydrochloride

[0980] Tert-butyl (2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)(methyl)carbamate (70 mg, 0.15 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.7 ml), and 2 M hydrochloric acid (0.30 mL) diluted in diethyl ether was added, followed by stirring at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (42 mg, 69%).

[0981] 1 H NMR (500 MHz, DMSO-d6) δ 11.42 (s, 1H), 9.16 (s, 1H), 8.41 (s, 1H), 7.22-7.18 (m, 1H), 7.13-7.11 (m, 2H), 6.99 (s, 1H), 6.53-6.52 (m, 1H), 4.31-4.30 (d, 2H), 4.04-4.03 (m, 2H), 2.66 (s, 2H), 2.41-2.37 (m, 12H)

[0982]

[0983] [Example 99] Preparation of 3-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)propanamide hydrochloride

[0984]

[0985] Step 1: Preparation of tert-butyl (3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl)carbamate

[0986] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol), Boc-beta-alanine (31 mg, 0.17 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (75 mg, 0.20 mmol), and diisopropylethylamine (0.11 mL, 0.61 mmol) were dissolved in dichloromethane (0.7 ml) and stirred at room temperature for 12 hours. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (70 mg, 99%).

[0987] Step 2: Preparation of 3-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)propanamide hydrochloride

[0988] Tert-butyl (3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl)carbamate (70 mg, 0.15 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.7 ml), and 2 M hydrochloric acid (0.30 mL) diluted in diethyl ether was added, followed by stirring at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (40 mg, 67%).

[0989] 1 H NMR (500 MHz, DMSO-d6) δ 10.88 (s, 1H), 8.49 (s, 1H), 8.01 (s, 1H), 7.21-7.13 (m, 3H), 7.01 (s, 1H), 6.46 (s, 1H), 4.31-4.30 (d, 2H), 3.12-3.09 (m, 2H), 2.86-2.83 (m, 2H), 2.40-2.37 (m, 12H)

[0990]

[0991] [Example 100] Preparation of N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-methoxyacetamide citrate

[0992]

[0993] N 8 -(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (Intermediate 2, 80 mg, 0.22 mmol) and triethylamine (0.092 mL, 0.66 mmol) were dissolved in dichloromethane (3.14 mL) and stirred at room temperature for 5 minutes. 2-Methoxyacetyl chloride (0.023 mL, 0.25 mmol) was slowly added dropwise and stirred at room temperature for 16 hours. The reaction was quenched by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (20 mg, 23%). After this, it was dissolved in acetone, citric acid (10 mg, 0.05 mmol) was added, and the mixture was stirred at room temperature for 12 hours. The resulting solid was filtered and dried to obtain the citrate salt of the target compound.

[0994] 1 H NMR (500 MHz, DMSO-d6) δ 9.76 (s, 1H), 8.28 (s, 1H), 7.21 (s, 1H), 6.98-6.96 (d, 2H), 6.67 (s, 1H), 5.34-5.33 (m, 1H), 4.27-4.26 (d, 2H), 4.03 (s, 2H), 3.41 (s, 3H), 2.72-2.60 (m, 4H), 2.32-2.26 (m, 12H)

[0995]

[0996] [Example 101] Preparation of N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-hydroxypropanamide citrate

[0997]

[0998] Step 1: Preparation of 3-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl acetate

[0999] N 8 -(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 2, 80 mg, 0.22 mmol), 3-acetoxypyropionic acid (31 mg, 0.24 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (108 mg, 0.28 mmol), and diisopropylethylamine (0.15 mL, 0.88 mmol) were dissolved in dichloromethane (3.1 mL), and the mixture was stirred at room temperature for 12 hours. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (20 mg, 22%).

[1000] Step 2: Preparation of N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-hydroxypropanamide citrate

[1001] 3-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl acetate (20 mg, 0.046 mmol) prepared in Step 1 above was dissolved in tetrahydrofuran (0.22 mL), methanol (0.22 mL), and distilled water (0.22 mL), potassium hydroxide (13 mg, 0.23 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The solvent was removed, distilled water was added to stop the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (10 mg, 56%). After this, it was dissolved in acetone, citric acid (5 mg, 0.025 mmol) was added, and the mixture was stirred at room temperature for 12 hours. The resulting solid was filtered and dried to obtain the citrate salt of the target compound.

[1002] 1 H NMR (500 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.28 (s, 1H), 6.97-6.95 (d, 2H), 6.32 (s, 1H), 5.20 (s, 1H), 4.26-4.25 (d, 2H), 3.73-3.72 (m, 2H), 2.64-2.58 (m, 4H), 2.36-2.23 (m, 12H)

[1003]

[1004] [Example 102] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-hydroxypropanamide citrate

[1005]

[1006] Step 1: Preparation of 3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl acetate

[1007] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 1.0 g, 3.03 mmol), 3-acetoxypyropionic acid (0.33 mL, 3.33 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (1.49 g, 3.93 mmol), and diisopropylethylamine (1.5 mL, 9.09 mmol) were dissolved in dichloromethane (30 mL) and stirred at room temperature for 16 h. Distilled water was added to quench the reaction, and extraction was performed with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. After the residue was purified by column chromatography, it was dissolved in dichloromethane and diethyl ether was added to precipitate a solid to obtain the target compound (0.6 g, 49%).

[1008] Step 2: Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-hydroxypropanamide citrate

[1009] 3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl acetate (600 mg, 1.47 mmol) prepared in Step 1 above was dissolved in tetrahydrofuran (4.9 mL), methanol (4.9 mL), and distilled water (4.9 mL), potassium hydroxide (411 mg, 7.35 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The solvent was removed, distilled water was added to stop the reaction, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the residue was precipitated as a solid by adding dichloromethane to obtain the target compound (238 mg, 44%). After this, it was dissolved in acetone, citric acid (124 mg, 0.65 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The resulting solid was filtered and dried to obtain the citrate salt of the target compound.

[1010] 1 H NMR (500 MHz, DMSO-d6) δ 9.93 (s, 1H), 8.31 (s, 1H), 7.18-7.11 (m, 3H), 6.37 (s, 1H), 5.33-5.32 (m, 1H), 4.72-4.71 (d, 2H), 3.74-3.73 (m, 2H), 2.68-2.56 (m, 4H), 2.35-2.24 (m, 12H)

[1011]

[1012] [Example 103] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-1-carboxamide hydrochloride

[1013]

[1014] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 70 mg, 0.21 mmol) and 1,1'-carbonyldiimidazole (68 mg, 0.42 mmol) were dissolved in dichloromethane (1.05 mL) and stirred at room temperature for 1 h. Tert-Butyl piperazine-1-carboxylate (39 mg, 0.21 mmol) and triethylamine (0.08 mL, 0.63 mmol) were added and stirred at room temperature for 6 h. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography, dissolved in ethyl acetate, and 4 N hydrochloric acid (0.42 mL) diluted in 1,4-dioxane was added. The mixture was stirred at room temperature for 6 hours. The resulting solid was filtered and dried to obtain the target compound (19 mg, 20%).

[1015] 1H NMR (500 MHz, DMSO-d6) δ 9.37-9.33 (m, 2H), 8.33 (s, 1H), 7.28-13 (m, 4H), 6.34 (s, 1H), 4.31-4.30 (d, 2H), 3.80-3.78 (m, 4H), 3.17-3.16 (m, 4H), 2.39-2.37 (m, 12H)

[1016]

[1017] [Example 104] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)benzamide citrate

[1018]

[1019] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 80 mg, 0.24 mmol), benzoic acid (29 mg, 0.24 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (118 mg, 0.31 mmol), and diisopropylethylamine (0.12 mL, 0.72 mmol) were dissolved in dichloromethane (3.4 mL) and stirred at room temperature for 12 hours. Distilled water was added to quench the reaction, and extraction was performed with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography, dissolved in acetone, and citric acid (11 mg, 0.06 mmol) was added. The mixture was stirred at room temperature for 12 hours. The resulting solid was filtered and dried to obtain the target compound (20 mg, 14%).

[1020] 1H NMR (500 MHz, DMSO-d6) δ 10.41 (s, 1H), 8.56 (s, 1H), 8.03-8.01 (d, 2H), 7.66-7.57 (m, 3H), 7.22-7.13 (m, 4H), 4.35-4.34 (d, 2H), 2.75-2.63 (m, 4H), 2.40-2.34 (m, 12H)

[1021]

[1022] [Example 105] Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)pyrrolidine-3-carboxamide hydrochloride

[1023]

[1024] Step 1: Preparation of tert-butyl (S)-3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)pyrrolidine-1-carboxylate

[1025] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol), (S)-1-bak-3-pyrrolidinecarboxylic acid (36 mg, 0.17 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (75 mg, 0.20 mmol), and diisopropylethylamine (0.11 mL, 0.61 mmol) were dissolved in dichloromethane (0.7 ml) and stirred at room temperature for 12 hours. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (72 mg, 96%).

[1026] Step 2: Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)pyrrolidine-3-carboxamide hydrochloride

[1027] Tert-butyl (S)-3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)pyrrolidine-1-carboxylate (72 mg, 0.15 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.73 mL), and 2 M hydrochloric acid (0.29 mL) diluted in diethyl ether was added, followed by stirring at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (52 mg, 83%).

[1028] 1 H NMR (500 MHz, DMSO-d6) δ 10.91-10.74 (m, 1H), 9.19-9.11 (m, 2H), 8.50-8.42 (m, 1H), 7.22-7.14 (m, 4H), 5.34-5.32 (m, 1H), 4.31-4.30 (d, 2H), 2.43-2.40 (m, 12H), 2.38-2.37 (m, 2H), 2.09-2.01 (m, 4H)

[1029]

[1030] [Example 106] Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-2-carboxamide hydrochloride

[1031]

[1032] Step 1: Preparation of tert-butyl (S)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)piperidine-1-carboxylate

[1033] N 8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol), (S)-1-bak-piperidine-2-carboxylic acid (38 mg, 0.17 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (75 mg, 0.20 mmol), and diisopropylethylamine (0.11 mL, 0.61 mmol) were dissolved in dichloromethane (0.7 ml) and stirred at room temperature for 12 hours. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (75 mg, 98%).

[1034] Step 2: Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-2-carboxamide hydrochloride

[1035] Tert-butyl (S)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)piperidine-1-carboxylate (75 mg, 0.15 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.7 ml), and 2 M hydrochloric acid (0.30 mL) diluted in diethyl ether was added, followed by stirring at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (59 mg, 89%).

[1036] 1H NMR (500 MHz, DMSO-d6) δ 11.32 (s, 1H), 9.35-9.33 (m, 1H), 8.89-8.87 (m, 1H), 8.44 (s, 1H), 7.23-7.14 (m, 3H), 7.04 (s, 1H), 6.45 (s, 1H), 4.31-4.30 (d, 2H), 4.03-4.02 (m, 1H), 3.07-3.05 (m, 2H), 2.42-2.31 (m, 14H), 1.69-1.64 (m, 4H)

[1037]

[1038] [Example 107] Preparation of (E)-4-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-3-oxoprop-1-en-1-yl)phenyl acetate

[1039]

[1040] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 80 mg, 0.24 mmol), (E)-3-(4-acetoxyphenyl)acrylic acid (54 mg, 0.26 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (68 mg, 0.36 mmol), 1-hydroxybenzotriazole hydrate (48 mg, 0.36 mmol), and triethylamine (0.1 mL, 0.72 mmol) were dissolved in dichloromethane (1.2 mL) and stirred at room temperature for 12 hours. Distilled water was added to quench the reaction, and extraction was performed with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (22 mg, 19%).

[1041] 1H NMR (500 MHz, DMSO-d6) δ 9.95 (s, 1H), 7.17-7.06 (m, 7H), 6.09 (s, 1H), 5.19-5.18 (m, 1H), 5.11-5.10 (m, 1h), 4.32-4.31 (d, 2H), 2.37-2.24 (m, 12H), 2.11 (s, 3H)

[1042]

[1043] [Example 108] Preparation of (E)-4-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-3-oxoprop-1-en-1-yl)-2-methoxyphenyl acetate

[1044]

[1045] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 80 mg, 0.24 mmol), (E)-3-(4-ethoxy-3-methoxyphenyl)acrylic acid (61 mg, 0.26 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (59 mg, 0.31 mmol), 1-hydroxybenzotriazole hydrate (42 mg, 0.31 mmol), and diisopropylethylamine (0.2 mL, 1.20 mmol) were dissolved in dichloromethane (1.2 mL), and the mixture was stirred at room temperature for 12 hours. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (30 mg, 24%).

[1046] 1H NMR (500 MHz, DMSO-d6) δ 9.94 (s, 1H), 7.17-7.06 (m, 4H), 6.96-6.94 (d, 1H), 6.35-6.34 (d, 1H), 6.08 (s, 1H), 5.18-5.17 (d, 1H), 5.11-5.10 (m, 1H), 4.33-4.32 (d, 2H), 3.86-3.84 (m, 1H), 3.75 (s, 3H), 2.37-2.35 (m, 9H), 2.23 (s, 3H), 2.11 (s, 3H)

[1047]

[1048] [Example 109] Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)aziridine-2-carboxamide hydrochloride

[1049]

[1050] Step 1: Preparation of tert-butyl (S)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)aziridine-1-carboxylate

[1051] N 8 -(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 80 mg, 0.24 mmol), (S)-1-(tert-butoxycarbonyl)aziridine-2-carboxylic acid (50 mg, 0.26 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (118 mg, 0.31 mmol), and diisopropylethylamine (0.12 mL, 0.72 mmol) were dissolved in dichloromethane (3.42 mL), and the mixture was stirred at room temperature for 12 h. The reaction was quenched by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, then concentrated under reduced pressure. The residue was purified by column chromatography to obtain the target compound (31 mg, 28%).

[1052] Step 2: Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)aziridine-2-carboxamide hydrochloride

[1053] Tert-butyl (S)-2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)aziridine-1-carboxylate (30 mg, 0.06 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.3 mL), and 2 N hydrochloric acid (0.12 mL) diluted in diethyl ether was added, followed by stirring at room temperature for 16 hours. The resulting solid was filtered and dried to obtain the target compound (7 mg, 29%).

[1054] 1 H NMR (500 MHz, DMSO-d6) δ 8.34-8.33 (m, 2H), 7.21-7.10 (m, 4H), 4.32-4.30 (m, 2H), 4.29-4.26 (m, 1H), 4.24-4.21 (m, 1H), 2.38-2.34 (m, 12H)

[1055]

[1056] [Example 110] Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-1-(2-hydroxyacetyl)pyrrolidine-3-carboxamide citrate

[1057]

[1058] Step 1: Preparation of (S)-2-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)pyrrolidin-1-yl)-2-oxoethyl acetate

[1059] (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)pyrrolidine-3-carboxamide hydrochloride (Example 105, 40 mg, 0.093 mmol) and triethylamine (39 μL, 0.28 mmol) were dissolved in dichloromethane (0.47 mL), and the mixture was stirred at room temperature for 5 minutes. 2-Chloro-2-oxoethyl acetate (12 μL, 0.11 mmol) was slowly added dropwise, and the mixture was stirred at room temperature for 4 hours. The reaction was quenched by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (24 mg, 51%).

[1060] Step 2: Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-1-(2-hydroxyacetyl)pyrrolidine-3-carboxamide citrate

[1061] (S)-2-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)pyrrolidin-1-yl)-2-oxoethyl acetate (24 mg, 0.048 mmol) prepared in the above step 1 was dissolved in tetrahydrofuran (0.3 mL), methanol (0.3 mL), and distilled water (0.3 mL), potassium hydroxide (13 mg, 0.24 mmol) was added, and the mixture was stirred at room temperature for 5 hours. The solvent was removed, distilled water was added, and the reaction was terminated, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the target compound (21 mg, 97%) was obtained. After this, it was dissolved in acetone, citric acid (9 mg, 0.047 mmol) was added, and the mixture was stirred at room temperature for 12 hours. The resulting solid was filtered and dried to obtain the citrate salt of the target compound.

[1062] 1H NMR (500 MHz, DMSO-d6) δ 10.09-10.08 (m, 1H), 8.25 (s, 1H), 7.18-7.11 (m, 3H), 6.31-6.26 (m, 1H), 5.08 (s, 1H), 4.59-4.58 (m, 1H), 4.31-4.30 (d, 2H), 4.02 (s, 1H), 3.68-3.67 (m, 1H), 3.65-3.63 (m, 2H), 2.64-2.53 (m, 4H), 2.35-2.22 (m, 12H)

[1063]

[1064] [Example 111] Preparation of (R)-1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl acetate

[1065]

[1066] N 8 -(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 2, 80 mg, 0.22 mmol), (R)-2-acetoxypyropionic acid (32 mg, 0.24 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (130 mg, 0.34 mmol), and diisopropylethylamine (0.16 mL, 0.88 mmol) were dissolved in dichloromethane (3.14 mL), and the mixture was stirred at room temperature for 12 hours. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (45 mg, 48%).

[1067] 1H NMR (500 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.37 (s, 1H), 7.02-7.00 (d, 2H), 6.71 (s, 1H), 5.10-5.09 (m, 1H), 4.28-4.27 (d, 2H), 3.64-3.62 (m, 1H), 3.16-3.15 (m, 1H), 2.70 (s, 3H), 2.37-2.33 (m, 12H), 2.11 (s, 3H)

[1068]

[1069] [Example 112] Preparation of (S)-1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl acetate

[1070]

[1071] N 8 -(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 2, 80 mg, 0.22 mmol), (S)-2-acetoxypyropionic acid (29 mg, 0.22 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (110 mg, 0.29 mmol), and diisopropylethylamine (0.15 mL, 0.88 mmol) were dissolved in dichloromethane (3.14 mL) and stirred at room temperature for 16 hours. Distilled water was added to quench the reaction, and extraction was performed with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (45 mg, 48%).

[1072] 1H NMR (500 MHz, DMSO-d6) δ 10.31 (s, 1H), 8.39 (s, 1H), 7.21 (s, 1H), 7.00-6.98 (d, 2H), 6.67 (s, 1H), 5.10-5.07 (m, 1H), 4.28-4.27 (m, 2H), 2.70 (s, 3H), 2.37-2.34 (m, 12H), 2.11 (s, 3H)

[1073]

[1074] [Example 113] Preparation of 1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)cyclopropyl acetate

[1075]

[1076] N 8 -(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 2, 80 mg, 0.22 mmol), 1-acetoxycyclopropane-1-carboxylic acid (31 mg, 0.22 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (108 mg, 0.28 mmol), and diisopropylethylamine (0.15 mL, 0.88 mmol) were dissolved in dichloromethane (3.14 mL), and the mixture was stirred at room temperature for 16 hours. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (40 mg, 42%).

[1077] 1H NMR (500 MHz, DMSO-d6) δ 9.77 (s, 1H), 8.24 (s, 1H), 7.21 (s, 1H), 6.99-6.97 (d, 2H), 6.67 (s, 1H), 5.33-5.32 (m, 2H), 4.27-4.26 (d, 2H), 2.69 (s, 2H), 2.33-2.28 (m, 12H), 2.15 (s, 3H), 2.01-1.98 (m, 2H)

[1078]

[1079] [Example 114] Preparation of (S)-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide

[1080]

[1081] (S)-1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl acetate (Example 112, 20 mg, 0.04 mmol) was dissolved in tetrahydrofuran (0.4 mL), methanol (0.4 mL), and distilled water (0.4 mL), potassium hydroxide (13 mg, 0.23 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The solvent was removed, distilled water was added to stop the reaction, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (10 mg, 65%).

[1082] 1 H NMR (500 MHz, DMSO-d6) δ 9.52 (s, 1H), 8.28 (s, 1H), 6.96-6.94 (d, 2H), 5.82-5.81 (m, 1H), 4.27-4.26 (d, 2H), 4.18-4.16 (m, 1H), 2.35 (s, 6H), 2.29 (s, 3H), 2.21 (s, 3H)1.34-1.33 (d, 3H)

[1083]

[1084] [Example 115] Preparation of N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-1-hydroxycyclopropane-1-carboxamide

[1085]

[1086] 1-((8-((4-Fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)cyclopropyl acetate (Example 113, 30 mg, 0.068 mmol) was dissolved in tetrahydrofuran (0.68 mL), methanol (0.68 mL), and distilled water (0.68 mL), potassium hydroxide (19 mg, 0.34 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The solvent was removed, distilled water was added to quench the reaction, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography, dissolved in ethyl acetate, and hexane was added to precipitate a solid to obtain the target compound (16 mg, 59%).

[1087] 1 H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 8.26 (s, 1H), 6.96-6.94 (d, 2H), 6.70 (s, 1H), 6.59 (s, 1H), 5.02 (s, 1H), 4.28-4.27 (d, 2H), 2.35 (s, 6H), 2.78 (s, 3H), 2.22 (s, 3H), 1.18-1.17 (m, 2H), 0.99-0.98 (m, 2H)

[1088]

[1089] [Example 116] Preparation of 3-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazolidine[1,2-a]pyridin-6-yl)-1-methylimidazolidine-2,4-dione

[1090]

[1091] N 8 -(4-Fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 2, 60 mg, 0.17 mmol) and 1,1'-carbonyldiimidazole (55 mg, 0.34 mmol) were dissolved in dichloromethane (2 mL) and stirred at room temperature for 1 h. Methylglycine hydrochloride (21 mg, 0.17 mmol) and triethylamine (0.09 mL, 0.68 mmol) were added and stirred at room temperature for 12 h. The reaction was quenched by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (18 mg, 25%).

[1092] 1 H NMR (500 MHz, DMSO-d6) δ 7.61 (s, 1H), 6.95-6.93 (d, 2H), 6.20 (s, 1H), 5.23-5.21 (m, 1H), 4.26-4.25 (d, 2H), 4.14 (s, 2H), 2.95 (sm 3H), 2.35-2.26 (m, 12H)

[1093]

[1094] [Example 117] Preparation of (R)-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide

[1095]

[1096] (R)-1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl acetate (Example 111, 20 mg, 0.04 mmol) was dissolved in tetrahydrofuran (0.4 mL), methanol (0.4 mL), and distilled water (0.4 mL), potassium hydroxide (13 mg, 0.23 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The solvent was removed, distilled water was added to stop the reaction, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (10 mg, 65%).

[1097] 1 H NMR (500 MHz, DMSO-d6) δ 9.51 (s, 1H), 8.27 (s, 1H), 6.96-6.94 (d, 2H), 6.56 (s, 1H), 5.81-5.80 (d, 1H), 5.04 (s, 1H), 4.27-4.26 (d, 2H), 4.18-4.16 (m, 1H), 2.35 (s, 6H), 2.29 (s, 3H), 2.22 (s, 3H), 1.34-1.32 (d, 3H)

[1098]

[1099] [Example 118] Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-3-carboxamide hydrochloride

[1100]

[1101] Step 1: Preparation of tert-butyl (S)-3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)piperidine-1-carboxylate

[1102] N8-(2,6-Dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine hydrochloride (intermediate 1, 50 mg, 0.15 mmol), (S)-1-bak-piperidine-3-carboxylic acid (38 mg, 0.17 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-B]pyridinium 3-oxide hexafluorophosphate (75 mg, 0.20 mmol), and diisopropylethylamine (0.11 mL, 0.61 mmol) were dissolved in dichloromethane (0.7 ml) and stirred at room temperature for 12 h. Distilled water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (75 mg, 98%).

[1103] Step 2: Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-3-carboxamide hydrochloride

[1104] Tert-butyl (S)-3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)piperidine-1-carboxylate (75 mg, 0.15 mmol) prepared in the above step 1 was dissolved in ethyl acetate (0.7 ml), and 2 M hydrochloric acid (0.30 mL) diluted in diethyl ether was added, followed by stirring at 50°C for 12 hours. The resulting solid was filtered and dried to obtain the target compound (60 mg, 91%).

[1105] 1 H NMR (500 MHz, DMSO-d6) δ 10.78 (s, 1H), 8.52 (s, 1H), 7.22-7.13 (m, 3H), 6.56 (s, 1H), 4.31-4.30 (d, 2H), 3.13-3.10 (m, 4H), 2.40-2.34 (m, 12H), 1.90-1.58 (m, 4H)

[1106]

[1107] [Example 119] Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-(2-hydroxyacetamido)propanamide

[1108]

[1109] Step 1: Preparation of 2-((3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl)amino)-2-oxoethylacetate

[1110] 3-Amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)propanamide hydrochloride (Example 99, 28 mg, 0.069 mmol) and triethylamine (29 μL, 0.21 mmol) were dissolved in dichloromethane (0.35 mL), and the mixture was stirred at room temperature for 5 minutes. 2-Chloro-2-oxoethyl acetate (9 μL, 0.083 mmol) was slowly added dropwise, and the mixture was stirred at room temperature for 12 hours. The reaction was quenched by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (23 mg, 72%).

[1111] Step 2: Preparation of N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-(2-hydroxyacetamido)propanamide

[1112] 2-((3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl)amino)-2-oxoethyl acetate (23 mg, 0.050 mmol) prepared in the above step 1 was dissolved in tetrahydrofuran (0.3 mL), methanol (0.3 mL), and distilled water (0.3 mL), then potassium hydroxide (14 mg, 0.25 mmol) was added and stirred at room temperature for 2 hours. The solvent was removed, distilled water was added to terminate the reaction, and extraction was performed with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the target compound (15 mg, 71%) was obtained.

[1113] 1 H NMR (500 MHz, DMSO-d6) δ 9.93 (s, 1H), 8.22 (s, 1H), 7.84-7.82 (m, 1H), 7.17-7.09 (m, 3H), 6.24 (s, 1H), 5.54 (s, 1H), 4.98-4.97 (m, 1H), 4.30-4.29 (d, 2H), 3.81-3.80 (m, 2H), 3.61-3.60 (m, 1H), 3.42-3.41 (m, 2H), 2.56-2.55 (m, 2H), 2.35-2.21 (m, 12H)

[1114]

[1115] [Example 120] Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-1-(2-hydroxyacetyl)piperidine-3-carboxamide

[1116]

[1117] Step 1: Preparation of (S)-2-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)piperidin-1-yl)-2-oxoethyl acetate

[1118] (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-3-carboxamide hydrochloride (Example 118, 43 mg, 0.097 mmol) and triethylamine (41 μL, 0.29 mmol) were dissolved in dichloromethane (0.49 mL), and the mixture was stirred at room temperature for 5 minutes. 2-Chloro-2-oxoethyl acetate (13 μL, 0.12 mmol) was slowly added dropwise, and the mixture was stirred at room temperature for 5 hours. The reaction was quenched by adding distilled water, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, reduced pressure, and concentrated. The residue was purified by column chromatography to obtain the target compound (22 mg, 45%).

[1119] Step 2: Preparation of (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-1-(2-hydroxyacetyl)piperidine-3-carboxamide

[1120] (S)-2-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)piperidin-1-yl)-2-oxoethyl acetate (22 mg, 0.044 mmol) prepared in the above step 1 was dissolved in tetrahydrofuran (0.3 mL), methanol (0.3 mL), and distilled water (0.3 mL), potassium hydroxide (12 mg, 0.22 mmol) was added, and the mixture was stirred at room temperature for 3 hours. The solvent was removed, distilled water was added to stop the reaction, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the target compound (16 mg, 80%) was obtained.

[1121] 1H NMR (500 MHz, DMSO-d6) δ 9.98-9.97 (m, 1H), 8.24 (s, 1H), 7.17-7.09 (m, 3H), 6.88 (s, 1H), 4.97-4.96 (m, 1H), 4.55-4.44 (m, 1H), 4.31-4.30 (d, 2H), 4.16-4.01 (m, 2H), 3.78-3.68 (m, 1H), 2.33-2.19 (m, 12H), 2.10-2.08 (m, 2H), 1.75-1.71 (m, 2H)

[1122]

[1123] [Comparative Example 1]

[1124] The following compounds were prepared.

[1125]

[1126]

[1127] [Comparative Example 2]

[1128] The following compounds were prepared.

[1129]

[1130]

[1131] Experimental Example 1: Measurement of inhibitory activity against proton pump (H+,K+-ATPase) activity

[1132] The inhibitory ability of the compounds prepared in Preliminary Examples 1 and 2 and Examples 1 to 120 on proton pump activity was measured as follows.

[1133] Specifically, gastric vesicles were isolated from porcine stomachs, and the protein content of the vesicles was quantified using a BSA kit (Bio-Rad, 5000205). All reactions were performed in 96-well plates with a reaction volume of 80 mL containing 100 ng of vesicles. 10 mM valinomycin and test compounds were added at various concentrations to the reaction buffer (50 mM Tris-HEPES, 5 mM MgCl2, 8 mM KCl, pH 6.5) containing porcine gastric liver vesicles, and incubated at 37°C for 30 minutes. DMSO or test compounds at various concentrations were added after being diluted to a final DMSO concentration of 0.1%. Subsequently, 0.2 mM adenosine triphosphate (ATP) was added to the reaction buffer, and incubated at 37°C for 20 minutes. The reaction was stopped by adding 0.2% Tween 20, and then malachite green (Malachite green reagent, Sigma Aldrich, MAK307) was added and incubated at room temperature for 30 minutes. The optical density (OD) value was measured at 620 nm using a microplate reader (Specramax M5e, Molecular devices). The inhibition rate (% inhibition) was derived from the OD value of the control group and the OD values ​​of various concentrations of the test compound, and the IC of the test compound 50 Nonlinear regression analysis was performed using the % inhibition value for each concentration using the GraphPad Prism8 program. The results are shown in Table 1 below.

[1134] (AA < 50 nM, 50 nM ≤ A < 100 nM, 100 nM ≤ B < 500 nM, 500 nM ≤ C)

[1135]

[1136] Number IC 50 (nM) number IC 50 (nM) number IC50 (nM) Example 1B Example 43AA Example 85B Example 2B Example 44AA Example 86AA Example 3C Example 45AA Example 87AA Example 4AA Example 46A Example 88AA Example 5B Example 47A Example 89A Example 6A Example 48A Example 90A Example 7B Example 49AA Example 91A Example 8C Example 50AA Example 92C Example 9C Example 51AA Example 93AA Example 10AA Example 52B Example 94AA Example 11B Example 53B Example 95AA Example 12B Example 54B Example 96B Embodiment 13A Embodiment 55C Embodiment 97A Embodiment 14B Embodiment 56C Embodiment 98A Embodiment 15AA Embodiment 57B Embodiment 99A Embodiment 16B Embodiment 58B Embodiment 100AA Embodiment 17B Embodiment 59B Embodiment 101AA Embodiment 18C Embodiment 60AA Embodiment 102AA Embodiment 19A Embodiment 61A Embodiment 103B Embodiment 20A Embodiment 62B Embodiment 104B Embodiment 21AA Embodiment 63A Embodiment 105B Embodiment 22A Embodiment 64AA Embodiment 106B Embodiment 23A Embodiment 65A Embodiment 107C Embodiment 24AA Embodiment 66B Embodiment 108C Embodiment 25B Embodiment 67A Embodiment 109B Embodiment 26AA Embodiment 68A Embodiment 110B Embodiment 27A Embodiment 69AA Embodiment 111B Embodiment 28C Embodiment 70B Embodiment 112C Embodiment 29C Embodiment 71B Embodiment 113B Embodiment 30B Embodiment 72B Embodiment 114B Embodiment 31B Embodiment 73B Embodiment 115AA Embodiment 32A Embodiment 74A Embodiment 116A Embodiment 33AA Embodiment 75B Embodiment 117AA Embodiment 34C Embodiment 76A Embodiment 118B Embodiment 35A Example 77AA Example 119A Example 36A Example 78B Example 120B Example 37A Example 79B Preliminary Example 1A Example 38C Example 80C Preliminary Example 2A Example 39C Example 81A Comparative Example 1B Example 40B Example 82B Comparative Example 2C Example 41C Example 83B Tegoprazan C Example 42B Example 84B

[1137] As shown in Table 1, the compounds prepared in Preliminary Examples 1 and 2 and Examples 1 to 120 were all confirmed to have inhibitory activity against proton pump activity. They were confirmed to have inhibitory activity against proton pump activity that was equivalent to or greater than that of Tegoprazan, a previously known representative proton pump inhibitor. On the other hand, the compounds prepared in Comparative Examples 1 and 2 were confirmed to have reduced inhibitory activity against proton pump activity.

[1138] Among the compounds prepared in Preliminary Examples 1 and 2 and Examples 1 to 120, the compounds prepared in Examples 4, 10, 15, 21, 24, 26, 33, 43-45, 49-51, 60, 64, 77, 86-88, 93-95, 100-102, 115, and 117 were confirmed to have excellent inhibitory abilities against proton pump activity.

[1139]

[1140] Experimental Example 2: Measurement of the inhibitory effect on basal gastric acid secretion in pylorus-ligated rats.

[1141] The Shay's rat model was applied to evaluate the inhibitory ability of the compounds prepared in Examples 4, 15, 21, 26, 45, 60, 86, 100, 101, and 102 on basal gastric acid secretion.

[1142] Specifically, male Sprague Dawley (SD) rats (weighing 180-220 g) were fasted for 24 h with only water, and then randomly assigned to groups (n=4-5) after measuring body weight. The negative control group was orally administered 2 mL / kg of 10% dimethylsulfoxide (DMSO) / 10% Cremophor EL / 80% DW, and the test group was orally administered the test compound at a dose of 2 mg / kg / 2 mL. One hour after administration, the rats' abdominal cavity was incised under isoflurane anesthesia, the stomach was exposed, and the pylorus was ligated. Three hours after ligation, the test animals were sacrificed and the stomach contents were collected by laparotomy again. The contents were centrifuged (3,000 rpm, 10 min), and only the supernatant was separated to obtain gastric juice. Afterwards, gastric fluid volume measurement, gastric fluid pH measurement, NaOH titration, and total gastric acid secretion calculation (gastric fluid volume × 0.1 N NaOH titer × 100) were sequentially performed. The final % inhibitory activity of the test compound was calculated according to the following formula. The results are shown in Table 2 below.

[1143]

[1144] % inhibitory activity of test compound = [(total gastric acid secretion of negative control group - total gastric acid secretion of test compound treated group) / total gastric acid secretion of negative control group] × 100

[1145] (A ≥ 90%, 90% > B ≥ 80%, 80% > C ≥ 70%)

[1146]

[1147] Number GERD (rat / mpk) Number GERD (rat / mpk) Example 4A Example 60A Example 15A Example 86A Example 21A Example 100A Example 26A Example 101C Example 45A Example 102A

[1148]

[1149] As shown in Table 2, the compounds prepared in Examples 4, 15, 21, 26, 45, 60, 86, 100, 101, and 102 were all found to have inhibitory effects on basal gastric acid secretion in pyloric-ligated rats. Meanwhile, Example 101 has considerable structural similarity to Example 102, but its inhibitory effect is somewhat reduced due to the substituted fluorine group.

[1150]

[1151] The foregoing description of the present invention is provided for illustrative purposes only. Those skilled in the art will readily appreciate that the present invention can be readily modified into other specific forms without altering the technical spirit or essential characteristics of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive.

Claims

1. An imidazopyridine compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof: [Chemical Formula 1] In the above chemical formula 1, R1 is , , , , or And, At this time, R 1a Inland R 1k is independently hydrogen, a cyano group, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C1 to C30 heteroalkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C2 to C30 alkynyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group, or R 1a Inland R 1k Among them, adjacent groups are connected to each other to form a substituted or unsubstituted aliphatic ring structure or a substituted or unsubstituted aromatic ring structure; R2 is -NR 2a R 2b And, at this time, R 2a R 2b is independently hydrogen, a cyano group, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C2 to C30 alkynyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group; R3 or R4 is independently hydrogen, a cyano group, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C2 to C30 alkenyl group, a substituted or unsubstituted C2 to C30 alkynyl group, a substituted or unsubstituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C7 to C30 arylalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, or a substituted or unsubstituted C3 to C30 heteroarylalkyl group.

2. In paragraph 1, The above R1 is , , or And, At this time, R 1c Inland R 1i is independently hydrogen, a substituted or unsubstituted C1 to C12 alkyl group, a substituted or unsubstituted C1 to C12 heteroalkyl group, a substituted or unsubstituted C3 to C12 cycloalkyl group, a substituted or unsubstituted C6 to C12 aryl group, a substituted or unsubstituted C7 to C12 arylalkyl group, a substituted or unsubstituted C2 to C12 heteroaryl group, or a substituted or unsubstituted C3 to C12 heteroarylalkyl group, or R 1c Inland R 1i An imidazopyridine compound or a pharmaceutically acceptable salt thereof, characterized in that adjacent groups among them are connected to each other to form a substituted or unsubstituted 12-membered or less aliphatic ring structure or a substituted or unsubstituted 12-membered or less aromatic ring structure.

3. In paragraph 1, The above R2 is -NR 2a R 2b And, at this time, R 2a is hydrogen, and R 2b An imidazopyridine compound or a pharmaceutically acceptable salt thereof, characterized in that it is a substituted or unsubstituted C7 to C12 arylalkyl group.

4. In paragraph 1, An imidazopyridine compound or a pharmaceutically acceptable salt thereof, characterized in that the above R3 or R4 is independently hydrogen or a substituted or unsubstituted C1 to C12 alkyl group.

5. In paragraph 1, The above compound or a pharmaceutically acceptable salt thereof (1) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclopentanecarboxamide; (2) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclopropanecarboxamide; (3) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclohexanecarboxamide; (4) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide; (5) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclobutanecarboxamide; (6) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-1-carboxamide; (7) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)isobutyramide; (8) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)pivalamide; (9) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2,2-difluoroacetamide; (10) 2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide; (11) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)pyrrolidine-1-carboxamide; (12) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)bicyclo[1.1.1]pentane-1-carboxamide; (13) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)propionamide; (14) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)oxazole-2-carboxamide; (15) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methoxyacetamide; (16) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2,2-difluoropropanamide; (17) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-fluorocyclobutane-1-carboxamide; (18) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)cyclobutanesulfonamide; (19) (S)-2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)propanamide; (20) (R)-2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)propanamide; (21) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide; (22) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-ethylurea; (23) 1-Cyclobutyl-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea; (24) 1-Cyclopropyl-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea; (25) 2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl acetate; (26) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-hydroxyacetamide; (27) 2-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methylpropanamide; (28) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidin-2-one; (29) 1-(bicyclo[1.1.1]pentan-1-yl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea; (30) 1-(cyclopropylmethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea; (31) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-isopropylurea; (32) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-ethyl-1-methylurea; (33) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-ethyl-1-methylurea; (34) 3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-3-oxopropanoate; (35) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide; (36) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide; (37) 1-(2-aminoethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea; (38) 4-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-4-oxobutanoic acid; (39) 3-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl)propanoic acid; (40) Ethyl 4-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-4-oxobutanoate; (41) tert-Butyl 3-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-3-oxopropyl)propanoate; (42) tert-butyl (2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)ethyl)carbamate; (43) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,1-dimethylurea; (44) 1-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-methylurea; (45) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide; (46) Methyl((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)carbamoyl)glycinate; (47) 2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)-N-methylacetamide; (48) 2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)-N,N-dimethylacetamide; (49) 3-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,1-dimethylurea; (50) 1-Cyclopropyl-3-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)urea; (51) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)azetidine-1-carboxamide; (52) 2-Acetamido-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide; (53) 2-(dimethylamino)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)acetamide; (54) 1-Butyl-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)urea; (55) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)pivalamide; (56) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-2,2-difluoroacetamide; (57) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-2,2-difluoropropanamide; (58) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-3-hydroxycyclobutane-1-carboxamide; (59) N-(2-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)amino)-2-oxoethyl)-3-fluorocyclobutane-1-carboxamide; (60) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)imidazolidine-2,4-dione; (61) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)morpholine-4-carboxamide; (62) 2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)ureido)ethyl acetate; (63) (S)-2-amino-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)propanamide; (64) 2-amino-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)acetamide; (65) (S)-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)azetidine-2-carboxamide; (66) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-2-azaspiro[3.3]heptane-2-carboxamide; (67) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-2-azaspiro[3.3]heptane-2-carboxamide; (68) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; (69) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-3-oxoazetidine-1-carboxamide; (70) ((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)carbamoyl)glycine; (71) 3-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)propionic acid; (72) 3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1,3,5-triazepane-2,4-dione; (73) N-(2-(3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)ureido)ethyl)acetamide; (74) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-3-((tetrohydrofuran-3-yl)methyl)urea; (75) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-methylazetidine-2-carboxamide; (76) (R)-2-(azetidin-2-yl)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)acetamide; (77) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-phenylazetidine-1-carboxamide; (78) (S)-1-(2,3-dihydro-1H-inden-1-yl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)urea; (79) (S)-N2-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-N1-methylazetidine-1,2-dicarboxamide; (80) (R)-1-(2,3-dihydro-1H-inden-1-yl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)urea; (81) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(2-oxoazetidin-1-yl)acetamide; (82) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-4-phenylpiperidine-1-carboxamide; (83) N-(8-((2,6-dimethylbenzyl l)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-phenylpiperidine-1-carboxamide; (84) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-phenylpyrrolidine-1-carboxamide; (85) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-2-carboxamide; (86) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxyacetamide; (87) 1-(2-aminoethyl)-3-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-1-methylurea; (88) 1-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-3-(2-hydroxyethyl)urea; (89) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)pyrrolidine-3-carboxamide; (90) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-2-carboxamide; (91) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(pyrrolidin-2-yl)acetamide; (92) N 8 -(2,6-dimethylbenzyl)-N6-isopropyl-2,3-dimethylimadzo[1,2-a]pyridine-6,8-diamine; (93) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(pyrrolidin-2-yl)acetamide; (94) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-2-carboxamide; (95) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(2-hydroxyacetamido)acetamide; (96) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide; (97) (R)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide; (98) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-(methylamino)acetamide; (99) 3-amino-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)propanamide; (100) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-methoxyacetamide; (101) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-hydroxypropanamide; (102) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-3-hydroxypropanamide; (103) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperazine-1-carboxamide; (104) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)benzamide; (105) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)pyrrolidine-3-carboxamide; (106) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-2-carboxamide; (107) (E)-4-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)amino)-3-oxoprop-1-en-1-yl)phenyl acetate; (108) (E)-4-(3-((8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)amino)-3-oxoprop-1-en-1-yl)-2-methoxyphenyl acetate; (109) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)aziridine-2-carboxamide; (110) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-1-(2-hydroxyacetyl)pyrrolidine-3-carboxamide; (111) (R)-1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl acetate; (112) (S)-1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)amino)-1-oxopropan-2-yl acetate; (113) 1-((8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)carbamoyl)cyclopropyl acetate; (114) (S)-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide; (115) N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-1-hydroxycyclopropane-1-carboxamide; (116) 3-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimidazolidine[1,2-a]pyridin-6-yl)-1-methylimidazolidine-2,4-dione; (117) (R)-N-(8-((4-fluoro-2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)-2-hydroxypropanamide; (118) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadazo[1,2-a]pyridin-6-yl)piperidine-3-carboxamide; (119) N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-3-(2-hydroxyacetamido)propanamide; (120) (S)-N-(8-((2,6-dimethylbenzyl)amino)-2,3-dimethylimadzo[1,2-a]pyridin-6-yl)-1-(2-hydroxyacetyl)piperidine-3-carboxamide; (121) N 8 -(2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine; and (122) N 8 An imidazopyridine compound or a pharmaceutically acceptable salt thereof, characterized in that at least one is selected from the group consisting of -(4-fluoro-2,6-dimethylbenzyl)-2,3-dimethylimidazo[1,2-a]pyridine-6,8-diamine.

6. In paragraph 1, An imidazopyridine compound or a pharmaceutically acceptable salt thereof, characterized in that the compound or a pharmaceutically acceptable salt thereof has an inhibitory ability against proton pump activity.

7. A pharmaceutical composition for preventing or treating gastrointestinal inflammatory disease or gastric acid-related disease, comprising an imidazopyridine compound according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof as an active ingredient.

8. In paragraph 7, A pharmaceutical composition for preventing or treating gastrointestinal inflammatory diseases or gastric acid-related diseases, characterized in that the compound or a pharmaceutically acceptable salt thereof acts as a reversible proton pump inhibitor.

9. In paragraph 7, A pharmaceutical composition for preventing or treating gastrointestinal inflammatory diseases or gastric acid-related diseases, characterized in that the compound or a pharmaceutically acceptable salt thereof suppresses gastric acid secretion.

10. In paragraph 7, A pharmaceutical composition for preventing or treating a gastrointestinal inflammatory disease or gastric acid-related disease, characterized in that the gastrointestinal inflammatory disease or gastric acid-related disease is at least one selected from the group consisting of peptic ulcer, gastric / duodenal ulcer, nonsteroidal anti-inflammatory drug (NSAID)-induced ulcer, Helicobacter pylori infection, functional dyspepsia, Zollinger-Ellison syndrome, gastritis, gastroesophageal reflux disease (GERD), and non-erosive reflux disease (NERD).

11. A health functional food composition for preventing or improving gastrointestinal inflammatory disease or gastric acid-related disease, comprising an imidazopyridine compound according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof as an active ingredient.