IP Library › Granted Patent US 12,559,481
Granted Patent B2
US 12,559,481 · App. 18/063,766 · Granted Feb 24, 2026

Quinoline derivatives

Inventors: Walter Huebsch (Wuppertal, DE); Nils Griebenow (Dormagen, DE); Hans-Georg Schwarz (Dorsten, DE); Daniel Kulke (Leverkusen, DE); Claudia Boehm (Hannover, DE); Kirsten Boerngen (Cologne, DE); Bernd Alig (Koenigswinter, DE); Wei Zhuang (Monheim am Rhein, DE); Iring Heisler (Duesseldorf, DE); Thomas Ilg (Monheim am Rhein, DE); Johannes Koebberling (Neuss, DE); Adeline Koehler (Langenfeld, DE); Niels Lindner (Wuppertal, DE); Ulrich Goergens (Ratingen, DE); Claudia Welz (Dusseldorf, DE); Maike Hink (Vaihingen/Enz, DE)
Assignee: Elanco Animal Health GmbH
C07D405/14A61P33/10C07D405/12
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Quick Facts
Patent No.
US 12,559,481
App. No.
18/063,766
Granted
Feb 24, 2026
Kind
B2
Abstract

The present invention covers new quinoline compounds of general formula (I): in which A, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and Q are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment, control and/or prevention of diseases, in particular of helminth infections, as a sole agent or in combination with other active ingredients.

Claims (165)

1 . A compound of general formula (I):

wherein

A is A1

is 0,1, 2, 3, or 4,

R is selected from the group consisting of hydrogen, halogen, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, and C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms,

R p is selected from the group consisting of hydrogen and C 1 -C 4 -alkyl,

X is O,

Y is CR 7 R 8 ,

R 1 is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halogenocycloalkyl having 1 to 5 halogen atoms, —NH 2 , —NH—C 1 -C 4 -alkyl, and —N(C 1 -C 4 -alkyl) 2 ,

R 2 is selected from the group consisting of tetrahydro-2H-pyran-4-yl, 3,6 dihydro-2H-pyran-4-yl, and 3-fluoroazetidin-1-yl,

R 3 is hydrogen or C 1 -C 4 -alkyl,

R 4 is selected from the group consisting of hydrogen, halogen, and C 1 -C 4 -alkoxy,

R 5 is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, and C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms,

R 6 is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, and C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms,

R 7 is selected from the group consisting of hydrogen, fluorine, and C 1 -C 4 -alkyl,

R 8 is selected from the group consisting of hydrogen, fluorine, and C 1 -C 4 -alkyl,

R 10 is selected from the group consisting of hydrogen, —OH, C 1 -C 4 -alkyl, and C 1 -C 4 -alkoxy,

R 11 is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, and C 1 -C 4 -alkoxy,

Q is 2,3,5-trifluorophenyl,

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

2 . The compound according to claim 1 , wherein:

A is A1

is 0, 1, or 2,

R is selected from the group consisting of hydrogen, halogen, methyl, methoxy, and cyano,

R p is hydrogen,

X is O,

Y is CR 7 R 8 ,

R 1 is selected from the group consisting of hydrogen, —OH, C 1 -C 4 -alkyl, and C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halogenocycloalkyl having 1 to 5 halogen atoms, —NH 2 , —NH—C 1 -C 4 -alkyl, and —N(C 1 -C 4 -alkyl) 2 ,

R 2 is selected from the group consisting of tetrahydro-2H-pyran-4-yl, 3,6 dihydro-2H-pyran-4-yl, and 3-fluoroazetidin-1-yl,

R 3 is hydrogen or C 1 -C 4 -alkyl,

R 4 is selected from the group consisting of hydrogen, halogen, and C 1 -C 4 -alkoxy,

R 5 is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, and C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms,

R 6 is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, and C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms,

R 7 is hydrogen,

R 8 is hydrogen,

R 10 is selected from the group consisting of hydrogen and C 1 -C 4 -alkyl,

R 11 is selected from the group consisting of hydrogen and C 1 -C 4 -alkyl,

Q is 2,3,5-trifluorophenyl,

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

3 . The compound according to claim 1 , wherein:

A is A1

is 0, 1, or 2,

R is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methyl, methoxy, and cyano,

R p is hydrogen,

X is O,

Y is CR 7 R 8 ,

R 1 is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halogenocycloalkyl having 1 to 5 halogen atoms, —NH 2 , —NH—C 1 -C 4 -alkyl, and —N(C 1 -C 4 -alkyl) 2 ,

R 2 is selected from the group consisting of tetrahydro-2H-pyran-4-yl, 3,6 dihydro-2H-pyran-4-yl, and 3-fluoroazetidin-1-yl,

R 3 is hydrogen or C 1 -C 4 -alkyl,

R 4 is selected from the group consisting of hydrogen, halogen, and C 1 -C 4 -alkoxy,

R 5 is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms,

R 6 is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms,

R 7 is hydrogen,

R 8 is hydrogen,

R 10 is selected from the group consisting of hydrogen and methyl,

R 11 is selected from the group consisting of hydrogen and methyl,

Q is 2,3,5-trifluorophenyl,

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

4 . The compound according to claim 1 , wherein:

A is selected from the group consisting of

R 1 is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halogenocycloalkyl having 1 to 5 halogen atoms, —NH 2 , —NH—C 1 -C 4 -alkyl, and —N(C 1 -C 4 -alkyl) 2 ,

R 2 is selected from the group consisting of tetrahydro-2H-pyran-4-yl, 3,6 dihydro-2H-pyran-4-yl, and 3-fluoroazetidin-1-yl,

R 3 is hydrogen or C 1 -C 4 -alkyl,

R 4 is selected from the group consisting of hydrogen, halogen, and C 1 -C 4 -alkoxy,

R 5 is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, and C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms,

R 6 is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, and C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms,

Q is 2,3,5-trifluorophenyl,

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

5 . The compound according to claim 1 , wherein:

A is selected from the group consisting of

R 1 is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halogenocycloalkyl having 1 to 5 halogen atoms, —NH 2 , —NH—C 1 -C 4 -alkyl, and —N(C 1 -C 4 -alkyl) 2 ,

R 2 is selected from the group consisting of tetrahydro-2H-pyran-4-yl, 3,6 dihydro-2H-pyran-4-yl, and 3-fluoroazetidin-1-yl,

R 3 is hydrogen or C 1 -C 4 -alkyl,

R 4 is selected from the group consisting of hydrogen, halogen, and C 1 -C 4 -alkoxy,

R 5 is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, and C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms

R 6 is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, and C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms

Q is 2,3,5-trifluorophenyl,

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

6 . The compound according to claim 1 , wherein:

A1 is

R 1 is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halogenocycloalkyl having 1 to 5 halogen atoms, —NH 2 , —NH—C 1 -C 4 -alkyl, and —N(C 1 -C 4 -alkyl) 2

R 2 is selected from the group consisting of tetrahydro-2H-pyran-4-yl, 3,6 dihydro-2H-pyran-4-yl, and 3-fluoroazetidin-1-yl,

R 3 is hydrogen or C 1 -C 4 -alkyl,

R 4 is selected from the group consisting of hydrogen, halogen, and C 1 -C 4 -alkoxy,

R 5 is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, and C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms,

R 6 is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, and C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms,

Q is 2,3,5-trifluorophenyl,

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

7 . The compound according to claim 1 , wherein:

A1 is

R 1 is selected from the group consisting of hydrogen, —OH, methyl, trifluoromethyl, cyclopropyl, —NH 2 , methylamine, and dimethylamine,

R 2 is selected from the group consisting of tetrahydro-2H-pyran-4-yl, 3,6 dihydro-2H-pyran-4-yl, and 3-fluoroazetidin-1-yl,

R 3 is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, and iso-butyl,

R 4 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, and isopropoxy,

R 5 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, trifluoromethyl, 2,2,2-trifluoroethyl, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethoxy,

R 6 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, trifluoromethyl, 2,2,2-trifluoroethyl, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethoxy,

Q is 2,3,5-trifluorophenyl,

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

8 . The compound according to claim 1 , wherein:

A1 is

R 1 is hydrogen,

R 2 is selected from the group consisting of tetrahydro-2H-pyran-4-yl, 3,6 dihydro-2H-pyran-4-yl, and 3-fluoroazetidin-1-yl,

R 3 is hydrogen,

R 4 is selected from the group consisting of hydrogen, halogen, and C 1 -C 4 -alkoxy,

R 5 is hydrogen,

R 6 is hydrogen,

Q is 2,3,5-trifluorophenyl,

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

9 . The compound according to claim 1 , wherein:

A1 is

R 1 is hydrogen,

R 2 is selected from the group consisting of tetrahydro-2H-pyran-4-yl, 3,6 dihydro-2H-pyran-4-yl, and 3-fluoroazetidin-1-yl,

R 3 is hydrogen,

R 4 is selected from the group consisting of hydrogen, fluorine, chlorine, methoxy, and isopropoxy,

R 5 is hydrogen,

R 6 is hydrogen,

Q is 2,3,5-trifluorophenyl,

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

10 . The compound according to claim 1 , wherein:

R 1 is hydrogen,

R 3 is hydrogen,

R 4 is selected from the group consisting of hydrogen, halogen, and C 1 -C 4 -alkoxy,

R 5 is hydrogen,

R 6 is hydrogen,

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

11 . The compound according to claim 1 , wherein the compound is selected from the group consisting of:

12 . A method of preparing a compound of general formula (I) according to claim 1 said method comprising the step of allowing an intermediate compound of general formula 1N

in which A, R 1 , R 3 , R 4 , R 5 , R 6 , and Q are as defined for the compound of general formula (I) according to claim 1 ,

to react with a compound of general formula 1F:

R 2 H  1F,

in which R 2 is 3-fluoroazetidine,

thereby giving a compound of general formula (I)

in which A, R 1 , R 3 , R 4 , R 5 , R 6 , and Q are as defined for the compound of general formula (I) according to claim 1 and R 2 is 3-fluoroazetidine,

or the step of allowing an intermediate compound of general formula 1T:

in which A, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined for the compound of general formula (I) according to claim 1 , and in which Hal is halogen,

to react with a compound of general formula 1H

Q-B(OR) 2   1H,

in which Q is 2,3,5-trifluorophenyl, and each R may be individually H or Me or both R are pinacolate,

thereby giving a compound of general formula (I)

in which A, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and Q are as defined for the compound of general formula (I) according to claim 1 ,

or the step of allowing an intermediate compound of general formula 1W:

in which Q, R 2 , R 3 , R 4 , R 5 and R 6 are as defined for the compound of general formula (I) according to claim 1 ,

to react with a compound of general formula 1M

in which R 1 and A are as defined for the compound of general formula (I) according to claim 1 ,

thereby giving a compound of general formula (I)

in which A, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and Q are as defined for the compound of general formula (I) according to claim 1 ,

or the step of allowing an intermediate compound of general formula 1N

in which Q, A, R 1 , R 3 , R 4 , R 5 and R 6 are as defined for the compound of general formula (I) according to claim 1 ,

to react with a compound of general formula 2A:

R 2 Met-X  2A,

in which R 2 is 3,6-dihydro-2H-pyran-4-yl,

Met is magnesium or zinc, and X is chlorine, bromine or iodine,

thereby giving a compound of general formula (I)

in which A, R 1 , R 3 , R 4 , R 5 , R 6 , and Q are as defined for the compound of general formula (I) according to claim 1 and R 2 is 3,6-dihydro-2H-pyran-4-yl.

13 . A compound of general formula (II):

in which:

R 2 is —OH or as defined for the compound of general formula (I) according to any one of claims 1 to 10 ,

R 3 , R 4 , R 5 , R 6 , and Q are as defined for the compound of general formula (I) according to any one of claims 1 to 10 , and

R A is H or C 1 -C 4 -alkyl,

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

14 . A pharmaceutical composition comprising a compound of general formula (I) according to claim 1 and one or more pharmaceutically acceptable excipients.

15 . A method for control, treatment and/or prevention of a disease in humans and/or animals, comprising administering to a human or an animal in need thereof an amount of the compound of formula (I) according to claim 1 , or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of the foregoing, wherein the disease is a helminthic infection.

16 . A method for controlling helminth infections in humans and/or animals by administering an anthelminthically effective amount of at least one compound of formula (I) according to claim 1 to a human or an animal in need thereof.

17 . A method for control, treatment and/or prevention of a disease in humans and/or animals, comprising administering to a human or an animal in need thereof a pharmaceutical composition according to claim 14 , wherein the disease is a helminthic infection.

18 . A method according to claim 12 , wherein Hal in 1T is selected from the group consisting of chlorine, bromine and iodine.

Assignments (2)
CHANGE OF NAME Recorded Sep 19, 2024
From: BAYER ANIMAL HEALTH GMBH
To: ELANCO ANIMAL HEALTH GMBH
Reel/Frame 068995/0717 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 9, 2022
From: HUEBSCH, WALTER; GRIEBENOW, NILS; SCHWARZ, HANS-GEORG; KULKE, DANIEL; BOEHM, CLAUDIA; BOERNGEN, KIRSTEN; ALIG, BERND; ZHUANG, WEI; HEISLER, IRING; ILG, THOMAS; KOEBBERLING, JOHANNES; KOEHLER, ADELINE; LINDNER, NIELS; GOERGENS, ULRICH; WELZ, CLAUDIA; HINK, MAIKE
To: BAYER ANIMAL HEALTH GMBH
Reel/Frame 062038/0379 →
Priority Claims (1)
EP 18171490 · May 9, 2018 · regional
Continuity (2)
Continuation 17053680
Related Publication 20230141809A1 · May 11, 2023
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