Granted Patent B2

US 12,655,124 · App. 17/783,947 · Granted Jun 16, 2026

Inventors: Magdalena Izabela Zawadzka (Gdansk, PL); Luigi Piero Stasi (Monza, IT); Maciej Krzysztof Rogacki (Cracow, PL); Grzegorz Wojciech Cwiertnia (Kamesznica, PL); Lukasz Piotr Dudek (Wieliczka, PL); Agnieszka Justyna Gibas (Cracow, PL); Anna Rajda (Wroclaw, PL); Charles-Henry Fabritius (Poznan, PL); Adam Radzimierski (Cracow, PL); Tushar Ravindra Mahajan (Cracow, PL); Marcin Wojciech Les (Mielec, PL); Karol Zuchowicz (Gnojnik, PL); Marek Wronowski (Debowa Góra, PL); David Jörg Synak (Cracow, PL); Sundara Raghuram Tangirala (Cracow, PL)

Assignee: RYVU THERAPEUTICS S.A.

C07D401/14A61P35/00C07D405/14C07D413/14C07D471/04

Abstract

Claims (140)

1 . A compound of formula (I)

or a salt, stereoisomer, tautomer, or N-oxide thereof,

wherein

X 1 is CH or N;

X 2 is CR 3 or N;

R 1 , R 2 and R 3 are independently H, OH, NR C R D , CN, halogen, C 1 -C 4 -alkyl, NR C R D —C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, aryloxy, benzyloxy, C(═O)R E , NR F C(═O)R E , NR F —(C 1 -C 4 -alkylene)-C(═O)R E , NR F —(C 1 -C 4 -alkylene)-NR C R D , O-(C 1 -C 4 -alkylene)-NR C R D , or 4- to 6-membered saturated, partially or fully unsaturated, or aromatic carbocyclyl, carbocyclyl-C 1 -C 2 -alkyl, heterocyclyl, heterocyclyloxy, or heterocyclyl-C 1 -C 2 -alkyl, or 8- to 10-membered saturated, partially or fully unsaturated, or aromatic carbobicyclyl or heterobicyclyl, wherein the aforementioned heterocyclic or heterobicyclic rings comprise one or more, same or different heteroatoms selected from O, N or S, wherein said N- and/or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or heteroatom in the aforementioned groups is independently unsubstituted or substituted with one or more, same or different substituents R X ;

R is a 5- or 6-membered aromatic carbocyclic or heterocyclic ring, or a 9- or 10-membered aromatic carbobicyclic or heterobicyclic ring, wherein the heterocyclic or heterobicyclic ring comprises at least one nitrogen atom and optionally one or more, same or different additional heteroatoms selected from O, N or S, wherein said N- and/or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or heteroatom in the aforementioned cyclic rings is independently unsubstituted or substituted with one or more same or different substituents RX;

R 5 is selected from the group consisting of

and wherein

R N is H, C 1 -C 4 -alkyl, HO(C═O)—C 1 -C 4 -alkyl, NR C R D —C 1 -C 4 -alkyl, C 1 -C 2 -alkoxy-C 1 -C 4 -alkyl, or a 3- or 4-membered saturated carbocyclyl or heterocyclyl, wherein said heterocyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N and/or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or heteroatom in the aforementioned groups is independently unsubstituted or substituted with one or more, same or different substituents R X ;

R C and R D are independently H, or C 1 -C 2 -alkyl; or

R C and R D together with the nitrogen atom to which they are bonded form a 5- or 6-membered saturated, partially or fully unsaturated, or aromatic heterocyclic ring, wherein said heterocyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and/or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or heteroatom in the heterocyclic ring is independently unsubstituted or substituted with one or more, same or different substituents RX;

R E is H, C 1 -C 2 -alkyl, NR C R D —C 1 -C 4 -alkyl, phenyl, benzyl, ORG, or NR H R I ; or a 5- or 6-membered saturated, partially or fully unsaturated heterocyclyl, wherein said heterocyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and/or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or heteroatom in the aforementioned groups is independently unsubstituted or substituted with one or more, same or different substituents RF;

R F is H, C 1 -C 2 -alkyl, C 3 -C 6 -cycloalkyl, phenyl, benzyl, or C(═O)NR H R I ;

R G is H, C 1 -C 2 -alkyl, or 5- or 6-membered aromatic carbocyclyl, carbocyclyl-C 1 -C 2 -alkyl, heterocyclyl, or heterocyclyl-C 1 -C 2 -alkyl, wherein the aforementioned heterocyclic rings comprise one or more, same or different heteroatoms selected from O, N or S, wherein said N-atoms are independently oxidized or non-oxidized;

R H and R I are independently H, C 1 -C 2 -alkyl, or 5- or 6-membered aromatic carbocyclyl, carbocyclyl-C 1 -C 2 -alkyl, heterocyclyl, or heterocyclyl-C 1 -C 2 -alkyl, wherein the aforementioned heterocyclic rings comprise one or more, same or different heteroatoms selected from O, N or S, wherein said N-atoms are independently oxidized or non-oxidized; or

R H and R I together with the nitrogen atom to which they are bonded form a 5- or 6-membered saturated, partially or fully unsaturated, or aromatic heterocyclic ring, wherein said heterocyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and/or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or heteroatom in the heterocyclic ring is independently unsubstituted or substituted with one or more, same or different substituents R X ;

R X is OH, NR C R D , halogen, CN, NO 2 , C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, NR C R D —C 1 -C 4 -alkyl, R C O—C 1 -C 4 -alkyl, C 1 -C 2 -alkoxy, C(═O)R E , or two R X form ═O, or two R X together with the carbon atom to which they are bonded form a 3- to 5-membered saturated, partially or fully unsaturated, or aromatic carbocyclic ring;

with the proviso that at least one of the following conditions is met:

any one of

R 1 , R 2 , or R 3 is independently NR C R D , NR C R D —C 1 -C 4 -alkyl, NR F —(C 1 -C 4 -alkylene)-NR C R D , O-(C 1 -C 4 -alkylene)-NR C R D , and R C is H;

or

any one of

R 1 , R 2 , or R 3 is NR F C(═O)R E , wherein RE is NR C R D —C 1 -C 4 -alkyl, and RC is H;

or

RN is NR C R D —C 1 -C 4 -alkyl and R C is H;

or

any one of the substituents R 1 , R 2 , R 3 , R 4 , R 5 , or RN carries a substituent R X , wherein

R X is OH, NR C R D , NR C R D —C 1 -C 4 -alkyl, or R C O—C 1 -C 4 -alkyl, and R C is H.

2 . The compound according to claim 1 , or the salt, stereoisomer, tautomer, or N-oxide thereof,

with the proviso that at least one of the following conditions is met:

R 2 is NHR D , NHR D —C 1 -C 4 -alkyl, NH-(C 1 -C 4 -alkylene)-NR C R D , NR F —(C 1 -C 4 -alkylene)-NHR D , O-(C 1 -C 4 -alkylene)-NHR D ;

or

R 2 is NR F C(═O)R E , wherein RE is NHR D —C 1 -C 4 -alkyl;

or

RN is NHR D —C 1 -C 4 -alkyl;

or

any one of the substituents R 2 , R 4 , R 5 , or RN carries a substituent R X , wherein

R X is OH, NHR D , NHR D —C 1 -C 4 -alkyl, or HO—C 1 -C 4 -alkyl.

3 . The compound according to claim 1 , or the salt, stereoisomer, tautomer, or N-oxide thereof,

with the proviso that at least one of the following conditions is met: either

R 2 is NH 2 , NH 2 —C 1 -C 2 -alkyl, NH-(C 1 -C 3 -alkylene)-NH 2 , NH-(C 1 -C 3 -alkylene)-NHCH 3 , NH—(C 1 -C 3 -alkylene)-N(CH 3 ) 2 , O-(C 1 -C 3 -alkylene)-NH 2 , or O-(C 1 -C 3 -alkylene)-NHCH 3 ;

or

R 2 is NHC(═O)R E , wherein RE is NH 2 —C 1 -C 4 -alkyl;

or

RN is NH 2 —C 1 -C 3 -alkyl;

or

any one of the substituents R 2 , R 4 , or R 5 carries a substituent R X , wherein

R X is OH, NH 2 , NHCH 3 , NH 2 —C 1 -C 2 -alkyl, or HO—C 1 -C 2 -alkyl.

4 . The compound according to claim 1 , or the salt, stereoisomer, tautomer, or N-oxide thereof, wherein

X 1 is CH; and

X 2 is CR 3 with R 3 being H.

5 . The compound according to claim 1 , or the salt, stereoisomer, tautomer, or N-oxide thereof, wherein

R 1 is H or F.

6 . The compound according to claim 1 , or the salt, stereoisomer, tautomer, or N-oxide thereof, wherein

R 2 is H, OH, NR C R D , CN, halogen, NR C R D —C 1 -C 4 -alkyl, NR F C(═O)R E , NR F —(C 1 -C 4 -alkylene)-C(═O)R E , NR F —(C 1 -C 4 -alkylene)-NR C R D , O-(C 1 -C 4 -alkylene)-NR C R D , or 4- to 6-membered saturated heterocyclyl, or 8- to 10-membered saturated heterobicyclyl, wherein the aforementioned heterocyclic or heterobicyclic rings comprise a nitrogen atom and optionally one or more, same or different heteroatoms selected from O, N or S, wherein said N- and/or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or heteroatom in the aforementioned groups is independently unsubstituted or substituted with one or more, same or different substituents R X .

7 . The compound according to claim 1 , or the salt, stereoisomer, tautomer, or N-oxide thereof, wherein

R N is H, C 1 -C 4 -alkyl, HO(C═O)-C 1 -C 3 -alkyl, NHR D —C 1 -C 3 -alkyl, C 1 -C 2 -alkoxy-C 1 -C 3 -alkyl, or cyclopropyl.

8 . The compound according to claim 1 , or the salt, stereoisomer, tautomer, or N-oxide thereof, wherein

R 4 is pyridinyl, wherein each substitutable carbon atom in the cyclic ring is independently unsubstituted or substituted by one or more, same or different substituents RX.

9 . The compound according to claim 1 , or the salt, stereoisomer, tautomer, or N-oxide thereof, wherein

R C is H or C 1 -C 2 -alkyl;

R D is H or C 1 -C 2 -alkyl;

R E is NH 2 —C 1 -C 4 -alkyl;

R F is H;

R X is halogen, OH, NH 2 , NHCH 3 , C 1 -C 2 -alkyl, C 1 -C 2 -alkoxy, NH 2 —C 1 -C 2 -alkyl, HO—C 1 -C 2 -alkyl, or two RX together with the carbon atom to which they are bonded form a 3-membered saturated carbocyclic ring.

10 . The compound according to claim 1 , wherein the compound according to formula (I) is selected from the group consisting of

3-({[(3S)-1-(6-aminopyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1-methyl-1,4-dihydroquinolin-4-one;

3-({[(3S)-1-(6-aminopyridin-3-yl)piperidin-3-yl][(2-methoxypyridin-4-yl)methyl]amino}methyl)-1-cyclopropyl-6,7-difluoro-1,4-dihydroquinolin-4-one;

7-[(3R)-3-aminopyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

7-[(3S)-3-aminopyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(3R)-3-hydroxypyrrolidin-1-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

7-[(3R)-3-(aminomethyl) pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

7-[(3S)-3-aminopiperidin-1-yl]-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one; and

7-[(3R)-3-aminopiperidin-1-yl]-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one, or the salt, stereoisomer, tautomer, or N-oxide thereof.

11 . The compound according to claim 1 , wherein the compound according to formula (I) is selected from the group consisting of

3-({[(3S)-1-(6-aminopyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1-methyl-1,4-dihydroquinolin-4-one;

3-({[(3S)-1-(6-aminopyridin-3-yl)piperidin-3-yl][(2-methoxypyridin-4-yl)methyl]amino}methyl)-1-cyclopropyl-6,7-difluoro-1,4-dihydroquinolin-4-one;

7-[(3R)-3-aminopyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

7-[(3S)-3-aminopyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(3R)-3-hydroxypyrrolidin-1-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

7-[(3R)-3-(aminomethyl) pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

7-[(3S)-3-aminopiperidin-1-yl]-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

7-[(3R)-3-aminopiperidin-1-yl]-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

3-({[(2-aminopyridin-4-yl)methyl][(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl]amino}methyl)-1-cyclopropyl-6,7-difluoro-1,4-dihydroquinolin-4-one;

7-amino-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

7-[(3S)-3-(aminomethyl) pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

7-{7-amino-5-azaspiro [2.4] heptan-5-yl}-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

3-({[(3S)-1-(6-aminopyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-6,7-difluoro-1-(propan-2-yl)-1,4-dihydroquinolin-4-one;

7-(4-amino-3,3-difluoropiperidin-1-yl)-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[3-(hydroxymethyl) azetidin-1-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(3R)-3-hydroxypiperidin-1-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

3-({[(3S)-1-(6-aminopyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-7-bromo-1-methyl-1,4-dihydroquinolin-4-one;

7-[3-(aminomethyl)-3-fluoropyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(3S)-3-hydroxypiperidin-1-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-(4-hydroxypiperidin-1-yl)-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[3-(methylamino) pyrrolidin-1-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

3-({[(3S)-1-(6-aminopyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1-(propan-2-yl)-1,4-dihydroquinolin-4-one;

7-amino-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydro-1,8-naphthyridin-4-one;

1-cyclopropyl-6-fluoro-7-[(3R)-3-hydroxypyrrolidin-1-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydro-1,8-naphthyridin-4-one;

1-cyclopropyl-6-fluoro-7-[(3S)-3-hydroxypyrrolidin-1-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

6-fluoro-7-[(3R)-3-hydroxypyrrolidin-1-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1-(propan-2-yl)-1,4-dihydro-1,8-naphthyridin-4-one;

1-cyclopropyl-7-[(3R)-3-hydroxypyrrolidin-1-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-(2-hydroxyethoxy)-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

7-[(3R)-3-hydroxypyrrolidin-1-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1-(propan-2-yl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(3R)-3-(methylamino) pyrrolidin-1-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

7-[(4R)-4-amino-3,3-difluoropiperidin-1-yl]-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

7-[(4S)-4-amino-3,3-difluoropiperidin-1-yl]-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(3S)-3-(methylamino) pyrrolidin-1-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(3R)-3-hydroxypyrrolidin-1-yl]-3-({[(2-methoxypyridin-4-yl)methyl][(3S)-1-(pyridin-3-yl)piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[2-(hydroxymethyl) morpholin-4-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(2S)-2-(hydroxymethyl) morpholin-4-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(2R)-2-(hydroxymethyl) morpholin-4-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-3-({[(3S,5S)-5-fluoro-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-7-(2-hydroxyethoxy)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(3R)-3-hydroxypyrrolidin-1-yl]-3-({[(2-methylpyridin-4-yl)methyl][(3S)-1-(pyridin-3-yl)piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[3-(hydroxymethyl) pyrrolidin-1-yl]-3-({[(3S)-1-(6-methylpyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(3S)-3-hydroxypiperidin-1-yl]-3-({[(3S)-1-(5-methylpyrazin-2-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-3-({[(3S,5S)-5-fluoro-1-(5-methylpyrazin-2-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-7-[(3S)-3-hydroxypiperidin-1-yl]-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-(2-hydroxyethoxy)-3-({[(2-methylpyridin-4-yl)methyl][(3S)-1-(pyridin-3-yl)piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-(2-hydroxyethoxy)-3-({[(2-methylpyridin-4-yl)methyl][(3S)-1-(pyrazin-2-yl)piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(3S)-3-hydroxypiperidin-1-yl]-3-({[(2-methylpyridin-4-yl)methyl][(3S)-1-(pyridin-3-yl)piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(3S)-3-(hydroxymethyl) pyrrolidin-1-yl]-3-({[(2-methylpyridin-4-yl)methyl][(3S)-1-(pyridin-3-yl)piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(3R)-3-(hydroxymethyl) pyrrolidin-1-yl]-3-({[(2-methylpyridin-4-yl)methyl][(3S)-1-(pyridin-3-yl)piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-3-({[(3S,5S)-5-fluoro-1-(pyridin-3-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-7-(2-hydroxyethoxy)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(3R)-3-(hydroxymethyl) pyrrolidin-1-yl]-3-({[(2-methylpyridin-4-yl)methyl][(3S)-1-(pyrazin-2-yl)piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-7-[(3S)-3-(hydroxymethyl) pyrrolidin-1-yl]-3-({[(2-methylpyridin-4-yl)methyl][(3S)-1-(pyrazin-2-yl)piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one;

1-cyclopropyl-6-fluoro-3-({[(3S,5S)-5-fluoro-1-(pyrazin-2-yl)piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-7-(2-hydroxyethoxy)-1,4-dihydroquinolin-4-one; and

1-cyclopropyl-6-fluoro-7-[(3S)-3-hydroxypiperidin-1-yl]-3-({[(2-methylpyridin-4-yl)methyl][(3S)-1-(pyrazin-2-yl)piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one, or the salt, stereoisomer, tautomer, or N-oxide thereof.

12 . A pharmaceutical composition comprising a pharmaceutically effective amount of the compound according to claim 1 , or a salt, stereoisomer, tautomer, or N-oxide thereof, and optionally a pharmaceutically acceptable carrier, diluent or excipient.

13 . The compound of claim 1 , or the salt, stereoisomer, tautomer, or N-oxide thereof, wherein X is CH; X 2 is CH or N; and R 1 is H or F.

14 . The compound of claim 13 , or the salt, stereoisomer, tautomer, or N-oxide thereof, wherein

R 2 is H, Br, F, C 1 , NH 2 ,

15 . The compound of claim 14 , or the salt, stereoisomer, tautomer, or N-oxide thereof, wherein

R 2 is H, Br, F, C 1 , or NH 2 .

16 . The compound of claim 14 , or the salt, stereoisomer, tautomer, or N-oxide thereof, wherein R 4 is methylpyridinyl, aminopyridinyl or methoxypyridinyl.

17 . The compound of claim 16 , or the salt, stereoisomer, tautomer, or N-oxide thereof, wherein R 4 is methylpyridinyl.

18 . The compound of claim 16 , or the salt, stereoisomer, tautomer, or N-oxide thereof, wherein R N is H, C 1 -C 4 -alkyl, HO(C═O)—C 1 -C 3 -alkyl, NH 2 —C 1 -C 3 -alkyl, C 1 -C 2 -alkoxy-C 1 -C 3 -alkyl, or cyclopropyl.

19 . The compound of claim 18 , or the salt, stereoisomer, tautomer, or N-oxide thereof, wherein R N is methyl or cyclopropyl.

20 . The compound of claim 18 , or the salt, stereoisomer, tautomer, or N-oxide thereof, wherein R 5 is

Assignments (1)

Priority Claims (1)

Continuity (1)

References Cited (101)