IP Library › Granted Patent US 12,377,088

Granted Patent B2

US 12,377,088 · App. 17/570,693 · Granted Aug 5, 2025

Substituted tetrahydroquinolinone compounds as ROR gamma modulators

Inventors: Ravi Kotrabasaiah Ujjinamatada (Anekal Taluk, IN); Chetan Pandit (Bangalore, IN)

A61K31/4709 A61K31/4985 A61K31/501 A61K31/506 C07D239/26 C07D401/04 C07D401/14 C07D403/04 C07D405/04 C07D409/04 C07D487/04

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 12,377,088
App. No.: 17/570,693
Granted: Aug 5, 2025
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present invention provides substituted tetrahydroquinolinone and related compounds of formula (I), which are therapeutically useful as modulators of Retinoic acid receptor-related orphan receptors (RORs), more particularly as RORγ modulators. These compounds are useful in the treatment and prevention of diseases and/or disorder, in particular their use in diseases and/or disorder mediated by RORγ receptor. The present invention also provides preparation of the compounds and pharmaceutical formulations comprising at least one of the substituted tetrahydroquinolinone or related compounds of formula (I), together with a pharmaceutically acceptable carrier, diluent or excipient therefor.

Claims (425)

1. A method of making a compound of Formula (I-1) or a pharmaceutically acceptable salt thereof, according to the following scheme:

wherein,

Het is a heterocyclyl; wherein the heterocyclyl is pyridyl, pyridazinyl, pyridazinone, pyrimidinyl, pyrazinyl, pyrazolyl, imidazopyrazinyl, imidazopyridyl, pyrrolopyrazinyl, thienyl, benzodioxolyl, benzimidazolyl, imidazopyridazinyl or tetrahydroisoquinolinonyl,

each Y 1 , Y 2 and Y 3 is independently CR a or N, wherein 0-2 of Y 1 , Y 2 and Y 3 are N;

Z 1 is CR a or N;

each R 1 , R 2 , R 6 and R 7 are independently hydrogen, halo or alkyl;

R 3 at each occurrence is independently hydroxy, halo, alkyl, alkoxy, haloalkyl or cycloalkyl; alternatively, two R 3 on the same carbon atom together form an oxo (═O) group;

R 4 is hydrogen, alkyl or alkoxy;

R 5 is alkyl, —(CH 2 ) n NR b R c or hydroxyalkyl;

R a is hydrogen, alkyl, alkoxy, halo, cycloalkyl or aryl;

R b and R c are each independently hydrogen or alkyl; alternatively, R b and R c on the same atom together form a ring;

m is 0 to 3;

n is 1;

B s is a base;

S v is a solvent;

C t is a transition metal catalyst; and

L g is a phosphorus-containing ligand.

2. The method of claim 1 , wherein the compound of Formula (I-1) is represented by formula (IE-1):

or a

pharmaceutically acceptable salt thereof.

3. The method of claim 1 , wherein Het is

4. The method of claim 1 , wherein is

5. The method of claim 1 , wherein

6. A method of making Compound-1 or a pharmaceutically acceptable salt thereof, according to the following scheme:

7. The method of claim 1 , wherein,

B s is K 2 CO 3 ;

S v is 1,4-dioxane;

C t is Palladium (II) acetate; and

L g is Xantphos.

8. The method of claim 1 , wherein the compound of Formula (I-1) is selected from the group consisting of:

Compound

No.

IUPAC Name

N-(4,6-dimethyl-5-oxo-6-(pyridin-2-yl)-5,6,7,8-tetrahydroquinolin-2-yl)-2-(4-

(ethylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxypyridin-3-yl)-6-methyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(6-(trifluoromethyl)pyridin-3-

yl)-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyridin-2-yl)-7,7-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(4-methoxypyridin-2-yl)-6-methyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(imidazo[1,2-a]pyrazin-8-yl)-6-methyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-

yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(6-methyl-5-oxo-6-(5-(trifluoromethyl)pyridin-2-yl)-5,6,7,8-tetrahydroquinolin-

2-yl)-2-(4-(methylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(2-methylimidazo[1,2-a]pyrazin-8-yl)-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(6-(5-chloropyridin-2-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)-2-(4-

(methylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(imidazo[1,2-a]pyrazin-8-yl)-3,6-dimethyl-5-

oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxypyridazin-3-yl)-6-methyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(6-(imidazo[1,2-a]pyridin-8-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-

yl)-2-(4-(methylsulfonyl)phenyl)acetamide;

N-(6-ethyl-6-(imidazo[1,2-a]pyrazin-8-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)-

2-(4-(ethylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(pyrrolo[1,2-a]pyrazin-1-yl)-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(6-methylimidazo[1,2-a]pyrazin-8-yl)-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxypyridin-3-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(4,6-dimethyl-5-oxo-6-(pyridin-3-yl)-5,6,7,8-tetrahydroquinolin-2-yl)-2-(4-

(ethylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxypyridin-2-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyridin-2-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(4-methoxypyrimidin-2-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(4-methoxypyridin-2-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-fluoropyridin-2-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(6-(5-chloro-3-methoxypyridin-2-yl)-4,6-dimethyl-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-methoxypyrimidin-5-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(imidazo[1,2-a]pyrazin-8-yl)-4,6-dimethyl-5-

oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyrazin-2-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(6-(2,6-dimethylpyrimidin-4-yl)-4,6-dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-

2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(6-(4,6-dimethylpyrimidin-2-yl)-4,6-dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-

2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-methoxypyrimidin-4-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxypyridazin-3-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(4,6-dimethyl-5-oxo-6-(5-(trifluoromethyl)pyridin-2-yl)-5,6,7,8-

tetrahydroquinolin-2-yl)-2-(4-(methylsulfonyl)phenyl)acetamide;

N-(6-(imidazo[1,2-a]pyrazin-8-yl)-4,6-dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-

2-yl)-2-(4-(methylsulfonyl)phenyl)acetamide;

N-(4,6-dimethyl-6-(6-methylpyridazin-3-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-

yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(6-(6-methoxypyridazin-3-yl)-4,6-dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-

yl)-2-(4-(methylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(4-hydroxypyrimidin-2-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-hydroxypyridin-4-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(6-(5-chloro-3-hydroxypyridin-2-yl)-4,6-dimethyl-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-hydroxypyridin-2-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-hydroxypyridin-3-yl)-6-methyl-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)acetamide;

N-(6-(6-ethylpyridazin-3-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)-2-

(4-(ethylsulfonyl)phenyl)acetamide;

N-(6-(benzo[d][1,3]dioxol-5-yl)-4,6-dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-

yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(4,6-dimethyl-6-(1-methyl-1H-benzo[d]imidazol-5-yl)-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(4,6-dimethyl-6-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(5-methylthiophen-2-yl)-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)acetamide;

N-(6-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-

2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(1H-pyrazol-1-yl)-5,6,7,8-

tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(imidazo[1,2-a]pyrazin-8-yl)-6,8-dimethyl-5-

oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(3-methylimidazo[1,2-a]pyrazin-8-yl)-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-isopropylpyrimidin-4-yl)-6-methyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(6-(2,6-dimethylimidazo[1,2-a]pyrazin-8-yl)-6-methyl-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(4,6-dimethyl-6-(2-methylimidazo[1,2-a]pyrazin-8-yl)-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(4,6-dimethyl-5-oxo-6-(6-(trifluoromethyl)pyridazin-3-yl)-5,6,7,8-

tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(imidazo[1,2-a]pyrazin-8-yl)-7-methyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(6-(trifluoromethyl)pyridazin-3-

yl)-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyrimidin-2-yl)-6-methyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-isopropoxypyridazin-3-yl)-6-methyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)-2-fluorophenyl)-N-(6-methyl-6-(2-methylimidazo[1,2-

a]pyrazin-8-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(6-methyl-6-(2-methylimidazo[1,2-a]pyrazin-8-yl)-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)-2-(4-(methylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-isopropylpyrazin-2-yl)-6-methyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyrimidin-2-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-isopropylpyridazin-3-yl)-6-methyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(6-(6-ethylpyridazin-3-yl)-4,6-dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)-

2-(4-(ethylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-methoxy-6-methylpyrimidin-4-yl)-6-methyl-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxy-2-methylpyrimidin-4-yl)-6-methyl-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-fluoro-2-methylimidazo[1,2-a]pyrazin-8-yl)-

6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(2-methyl-6-(trifluoromethyl)-

pyrimidin-4-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(5-methylimidazo[1,2-a]pyrazin-8-yl)-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(6-(2,6-dimethylpyrimidin-4-yl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-

2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(4,6-dimethyl-6-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(6-(3-cyclopropylimidazo[1,2-a]pyrazin-8-yl)-6-methyl-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(2-(trifluoromethyl)-

imidazo[1,2-a]pyrazin-8-yl)-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyridazin-3-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(3-(trifluoromethyl)-

imidazo[1,2-a]pyrazin-8-yl)-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(4,6-dimethyl-6-(2-methylimidazo[1,2-b]pyridazin-6-yl)-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(6-(5-cyclopropyl-6-methoxypyridazin-3-yl)-4,6-dimethyl-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(imidazo[1,2-b]pyridazin-6-yl)-4,6-dimethyl-5-

oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(6-methyl-2-(trifluoromethyl)-

pyrimidin-4-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-

yl)-2-(5-(ethylsulfonyl)pyridin-2-yl)acetamide;

2-(5-(ethylsulfonyl)pyridin-2-yl)-N-(6-(6-methoxypyridazin-3-yl)-4,6-dimethyl-5-

oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(6-(2,6-dimethylpyrimidin-4-yl)-6,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-

2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(6-(2,6-dimethylpyrimidin-4-yl)-7-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-

yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(7-(2,6-dimethylpyrimidin-4-yl)-7-methyl-8-oxo-5,6,7,8-tetrahydroisoquinolin-

3-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-hydroxypyridin-3-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-hydroxypyridin-2-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-hydroxy-4-methylpyridin-3-yl)-4,6-dimethyl-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-hydroxypyridin-2-yl)-7,7-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-hydroxypyridin-2-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(6-(3-hydroxypyridin-2-yl)-4,6-dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-

yl)-2-(4-(methylsulfonyl)phenyl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-hydroxypyridin-2-yl)-7,7-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-hydroxypyridin-2-yl)-7-methyl-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)acetamide;

N-(6-(5-chloroimidazo[1,2-a]pyrazin-8-yl)-6-methyl-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(6-(6-chloropyridazin-3-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)-2-

(4-(ethylsulfonyl)phenyl)acetamide;

3-(2-(2-(4-(ethylsulfonyl)phenyl)acetamido)-4,6-dimethyl-5-oxo-5,6,7,8-

tetrahydroquinolin-6-yl)-6-methoxypyridazine 1-oxide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxy-4-methylpyridazin-3-yl)-4,6-

dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxy-5-methylpyridazin-3-yl)-4,6-

dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-fluoroimidazo[1,2-a]pyrazin-8-yl)-6-methyl-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;

N-(6-(6-(dimethylamino)pyridazin-3-yl)-4,6-dimethyl-5-oxo-5,6,7,8-

tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

6-(2,6-dimethylpyrimidin-4-yl)-N-(4-(ethylsulfonyl)benzyl)-6-methyl-5-oxo-

5,6,7,8-tetrahydroquinoline-2-carboxamide;

100

N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydronaphthalen-

2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

101

2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-hydroxypyridin-2-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of Compound-84);

102

2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-hydroxypyridin-2-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of Compound-84);

103

N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-

yl)-2-(4-(ethylsulfonyl)phenyl)acetamide; (Isomer-1 of Compound-7);

104

N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-

yl)-2-(4-(ethylsulfonyl)phenyl)acetamide; (Isomer-2 of Compound-7);

105

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(2-methylimidazo[1,2-a]pyrazin-8-yl)-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of Compound-9);

106

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(2-methylimidazo[1,2-a]pyrazin-8-yl)-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of Compound-9);

107

N-(6-(2,6-dimethylpyrimidin-4-yl)-4,6-dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-

2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide; (Isomer-1 of Compound-28);

108

N-(6-(2,6-dimethylpyrimidin-4-yl)-4,6-dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-

2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide; (Isomer-2 of Compound-28);

109

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxypyridazin-3-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of Compound-31);

110

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxypyridazin-3-yl)-4,6-dimethyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of Compound-31);

111

2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyrimidin-2-yl)-6-methyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of Compound-56);

112

2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyrimidin-2-yl)-6-methyl-5-oxo-

5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of Compound-56);

113

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(3-methylimidazo[1,2-a]pyrazin-8-yl)-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of Compound-49);

114

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(3-methylimidazo[1,2-a]pyrazin-8-yl)-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of Compound-49);

115

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxy-2-methylpyrimidin-4-yl)-6-methyl-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of Compound-65);

116

2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxy-2-methylpyrimidin-4-yl)-6-methyl-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of Compound-65);

117

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(6-methylimidazo[1,2-a]pyrazin-8-yl)-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of Compound-16);

118

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(6-methylimidazo[1,2-a]pyrazin-8-yl)-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of Compound-16);

119

2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-methoxy-6-methylpyrimidin-4-yl)-6-methyl-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of Compound-64);

120

2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-methoxy-6-methylpyrimidin-4-yl)-6-methyl-

5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of Compound-64);

121

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(3-(trifluoromethyl)imidazo[1,2-

a]pyrazin-8-yl)-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of

Compound-74);

122

2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(3-(trifluoromethyl)imidazo[1,2-

a]pyrazin-8-yl)-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of

Compound-74);

123

N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-

yl)-2-(5-(ethylsulfonyl)pyridin-2-yl)acetamide; (Isomer-1 of Compound-79);

124

N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-

yl)-2-(5-(ethylsulfonyl)pyridin-2-yl)acetamide; (Isomer-2 of Compound-79);

or a pharmaceutically acceptable salt thereof.

9. A method of making Compound-99 or a pharmaceutically acceptable salt thereof, according to the following scheme:

comprising the step of coupling of intermediate-E with (4-(ethylsulfonyl) phenyl) methanamine in presence of a base and a coupling agent in a solvent.

10. The method of claim 9 , comprising an additional step of chiral separation of racemic compound.

11. The method of claim 9 , wherein,

the solvent is N,N-dimethyl formamide (DMF);

the base is N,N-Diisopropylethylamine (DIPEA); and

the coupling agent is an amide coupling agent 1-[Bis (dimethylamino) methylene]-1H-1,2,3-triazolo [4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU).

12. The method of claim 9 , wherein the intermediate-E is synthesized by a process comprising the steps of:

i) reacting intermediate-A with 4-bromo-2,6-dimethylpyrimidine in presence of sodium tert-butoxide and catalyst Pd(amphos)Cl 2 in toluene to afford intermediate-B,

ii) alkylating intermediate-B with methyl iodide in presence of base NaH in DMF to afford intermediate-C,

iii) cyanating intermediate-C with zinc cyanide in presence of catalyst tetrakis (triphenylphosphine) palladium (0) in dimethyl acetamide to afford intermediate-D,

and

iv) hydrolysing the intermediate-D in presence of concentrated HCl to afford intermediate-E,

13. The method of claim 9 , wherein the compound is 6-(2,6-dimethylpyrimidin-4-yl)-N-(4-(ethylsulfonyl) benzyl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinoline-2-carboxamide.

14. The method of claim 9 , wherein the compound is a(S)-enantiomer of 6-(2,6-dimethylpyrimidin-4-yl)-N-(4-(ethylsulfonyl) benzyl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinoline-2-carboxamide.

15. The method of claim 9 , wherein the compound is a (R)-enantiomer of 6-(2,6-dimethylpyrimidin-4-yl)-N-(4-(ethylsulfonyl) benzyl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinoline-2-carboxamide.

Assignments (2)

CHANGE OF NAME Recorded Jul 3, 2025

From: AURIGENE DISCOVERY TECHNOLOGIES LIMITED

To: AURIGENE ONCOLOGY LIMITED

Reel/Frame 071601/0504 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 26, 2025

From: UJJINAMATADA, RAVI KOTRABASAIAH; PANDIT, CHETAN

To: AURIGENE DISCOVERY TECHNOLOGIES LIMITED

Reel/Frame 071537/0290 →

Priority Claims (1)

IN 2448/CHE/2015 · May 15, 2015 · national

Continuity (3)

Continuation 16709692 · Dec 10, 2019

Continuation 15574243

Related Publication 20220125780A1 · Apr 28, 2022

References Cited (68)

US 9481674B1 · Claremon et al. · 2016 [cited by applicant]

US 9663515B2 · Claremon et al. · 2017 [cited by applicant]

US 9845308B2 · Claremon et al. · 2017 [cited by applicant]

US 9855229B2 · Khairatkar-Joshi et al. · 2018 [cited by applicant]

US 20160122318A1 · Claremon et al. · 2016 [cited by applicant]

US 20160122345A1 · Claremon et al. · 2016 [cited by applicant]

US 20160346234A1 · Khairatkar-Joshi et al. · 2016 [cited by applicant]

US 20180200247A1 · Ujjinamatada et al. · 2018 [cited by applicant]

EP 3294713A1 · 2018 [cited by applicant]

JP 2007533752A · 2007 [cited by applicant]

JP 2017505318A · 2017 [cited by applicant]

WO WO0246173A1 · 2002 [cited by applicant]

WO WO2005082856A2 · 2005 [cited by applicant]

WO WO2005103022A1 · 2005 [cited by applicant]

WO WO2012027965A1 · 2012 [cited by applicant]

WO WO2012028100A1 · 2012 [cited by applicant]

WO WO2012100732A1 · 2012 [cited by applicant]

WO WO2012100734A1 · 2012 [cited by applicant]

WO WO2013029338A1 · 2013 [cited by applicant]

WO WO2013166013A1 · 2013 [cited by applicant]

WO WO2013169588A1 · 2013 [cited by applicant]

WO WO2013171729A2 · 2013 [cited by applicant]

WO WO2014125426A1 · 2014 [cited by examiner]

WO WO2014179564A1 · 2014 [cited by applicant]

WO WO2016017335A1 · 2015 [cited by applicant]

WO WO2015035032A1 · 2015 [cited by applicant]

WO WO2015082533A1 · 2015 [cited by applicant]

WO WO2015083130A1 · 2015 [cited by applicant]

WO WO2015101928A1 · 2015 [cited by applicant]

WO WO2015116904A1 · 2015 [cited by applicant]

WO WO2015145371A1 · 2015 [cited by applicant]

WO WO2015159233A1 · 2015 [cited by applicant]

WO WO2015160654A1 · 2015 [cited by applicant]

WO WO2016061160A1 · 2016 [cited by applicant]

WO WO2016185342A1 · 2016 [cited by examiner]

WO WO2017010399A1 · 2017 [cited by applicant]

WO WO2017024018A1 · 2017 [cited by applicant]

WO WO2017087608A1 · 2017 [cited by applicant]

WO WO2017132432A1 · 2017 [cited by applicant]

“Extended European Search Report mailed on Sep. 26, 2018 in Europe Patent Application No. 16795974.1, filed on May 13, 2016”, 9 pages. [cited by applicant]

“International Preliminary Report on Patentability mailed on Nov. 30, 2017 in International Patent Application No. PCT/IB2016/052773, filed on May 13. 2016”, 8 pages. [cited by applicant]

“International Search Report and Written Opinion mailed on Sep. 5, 2016 in International Patent Application No. PCT/IB2016/052773, filed on May 13, 2016”, 10 pages. [cited by applicant]

“Office Action dated Sep. 11. 2019 in U.S. Appl. No. 15/574,243, filed Nov. 15, 2017 and published as US 2018-200247 A1 on Jul. 19, 2018”, 6 pages. [cited by applicant]

“Office Action dated Jan. 11, 2019 in U.S. Appl. No. 15/574,243, filed Nov. 15, 2017 and published as US 2018200247 A1, on Jul. 19, 2018”, 12 pages. [cited by applicant]

“Search Report mailed on Jan. 14, 2020 in Japanese Patent Application No. 2017-559113; filed on May 13, 2016”, 61 pages. (Including partial English translation from Japanese produced by machine translation provided on t… [cited by applicant]

Annunziato, et al., “Type 17 T Helper Cells-Origins, Features and Possible Roles in Rheumatic Disease”, Nature Reviews Rheumatology, 2009, 5:325-331. [cited by applicant]

Buonocore, et al., “Innate Lymphoid Cells Drive Interleukin-23-Dependent Innate Intestinal Pathology”, Nature, Apr. 29, 2010, 464(7293):1371-1375. [cited by applicant]

Chang, et al., “The Therapeutic Potential of RORγ Modulators in the Treatment of Human Disease”, Journal of Experimental Pharmacology, 2012, 4:141-148. [cited by applicant]

Eberl, et al., “An Essential Function for the Nuclear Receptor RORγt in the Generation of Fetal Lymphoid Tissue Inducer Cells”, Nature Immunology, Dec. 21, 2003, 5(1):64-73. [cited by applicant]

Figueroa-Vega, et al., “Increased Circulating Pro-Inflammatory Cytokines and Th17 Lymphocytes in Hashimoto's Thyroiditis”, The Journal of Clinical Endocrinology and Metabolism, Dec. 2009, 95(2):953-962. [cited by applicant]

He, et al., “RORγt, a Novel Isoform of an Orphan Receptor, Negatively Regulates Fas Ligand Expression and IL-2 Production in T Cells”, Immunity, Dec. 1998, 9(6):797- 806. [cited by applicant]

Hueber, et al., “Cutting Edge: Mast Cells Express IL-17A in Rheumatoid Arthritis Synovium”, Joumal of Immunology, 2010, 184(7):3336-3340. [cited by applicant]

Ivanov, et al., “The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells”, Cell, Sep. 22, 2006, 126(6):1121-1133. [cited by applicant]

Jetten, Anton M., “Retinoid-Related Orphan Receptors (RORs): Critical Roles in Development, Immunity, Circadian Rhythm, and Cellular Metabolism”, Nuclear Receptor Signaling, 2009, 7:1-32. [cited by applicant]

Jetten, et al., “Retinoid-related Orphan Receptors (RORs): Roles in Cellular Differentiation and Development”, Advances in Developmental Biology, 2006, 16:313-355. [cited by applicant]

Jetten, et al., “The ROR Nuclear Orphan Receptor Subfamily: Critical Regulators of Multiple Biological Processes”, Progress in Nucleic Acid Research and Molecular Biology, 2001. 69:205-247,. [cited by applicant]

Jia, et al., “The T Helper Type 17/Regulatory T Cell Imbalance in Patients with Acute Kawasaki Disease”, Clinical and Experimental Immunology, 2010, 162(1):131-137. [cited by applicant]

Kastelein, et al., “Discovery and Biology of IL-23 and IL-27: Related but Functionally Distinct Regulators of Inflammation”, Annual Review of Immunology, 2007, 25:221-242. [cited by applicant]

Korn, et al., “IL-17 and Th17 Cells”, Annual Review of Immunology, 2009, 27:485-517. [cited by applicant]

Leung, et al., “The Cytokine Milieu in the Interplay of Pathogenic Th1/Th17 Cells and Regulatory T Cells in Autoimmune Disease”, Cellular & Molecular Immunology, 2010, 7(3):182-189. [cited by applicant]

Louten, et al., “Development and Function of TH17 Cells in Health and Disease”, The Journal of Allergy and Clinical Immunology, May 2009, 123(5):1004-1011. [cited by applicant]

Manel, et al., “The Differentiation of Human TH-17 Cells Requires Transforming Growth Factor-β and Induction of the Nuclear Receptor RORγT”, Nature Immunology, Jun. 2008, 9(6):641-649. [cited by applicant]

Marelli, et al., “Tumor Targeting via Integrin Ligands”, Frontiers in Oncology, Aug. 2013, 3(222):1-12. [cited by applicant]

Miossec, et al., “Interleukin-17 and Type 17 Helper T Cells”, The New England Journal of Medicine, Aug. 27, 2009, 361:888-898. [cited by applicant]

Steinman, Lawrence, “A Rush to Judgment on Th17”, Journal of Experimental Medicine, 2008, 205(7):1517-1522. [cited by applicant]

Sutton, et al., “Interleukin-1 and IL-23 Induce Innate IL-17 Production from γδ T Cells, Amplifying Th17 Responses and Autoimmunity”, Immunity. Aug. 21, 2009, 31(2):331-341. [cited by applicant]

Wang, et al., “Mathematical Modeling in Cancer Drug Discovery”, Drug Discovery Today, 2013, 19(2): 145-150. [cited by applicant]

Zou, et al., “TH17 Cells in Tumour Immunity and Immunotherapy”, Nature Reviews Immunology. Apr. 2010, 10(4):248-256. [cited by applicant]