IP Library Granted Patent US 8,022,218
Granted Patent B2
US 8,022,218 · App. 11/912,736 · Granted Sep 20, 2011

4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives for the treatment of infertility

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Quick Facts
Patent No.
US 8,022,218
App. No.
11/912,736
Granted
Sep 20, 2011
Kind
B2
Abstract

The present invention relates to 4-phenyl-5-oxo-1,4)5,6,7,8-hexahydroquinoline derivatives according to Formula I, Formula I or a pharmaceutically acceptable salt thereof, wherein R 1 is (1-6C)alkyl, (2-6C)alkenyl or (2-6C)aDcynyl; R 2 , R 3 are independently halogen, (1-4C)allcyl, (2-4C)alkenyl, (2-4C)-alkynyl, (1-4C)aBcoxy, (3-4C)alkenyloxy or (3-4C)alkynyloxy; R 4 is phenyl or (2-5C)-heteroaryl, both substituted with R 7 and optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)alkylthio and (di)(1-4C)-alkylamino. The invention also relates to pharmaceutical compositions comprising said derivatives, as well as to the use of these 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydro-quinoline derivatives in therapy, more specifically for the treatment of infertility.

Claims (94)

1. A 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to Formula I,

or a pharmaceutically acceptable salt thereof, wherein

R 1 is (1-6C)alkyl, (2-6C)alkenyl or (2-6C)alkynyl;

R 2 , R 3 are independently halogen, (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkoxy, (3-4C)alkenyloxy or (3-4C)alkynyloxy;

R 4 is phenyl or (2-5C)heteroaryl, both substituted with R 7 and optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)alkylthio and (di)(1-4C)alkylamino;

R 7 is H, (1-4C)alkylthio, (1-4C)alkylsulfonyl, (di)(1-4C)alkylamino, R 8 R 9 -amino, R 10 R 11 -aminocarbonyl, R 12 R 13 -amino(1-4C)alkylcarbonylamino, R 14 R 15 -amino(1-4C)alkyl, R 16 -oxy, R 17 R 18 -aminocarbonyl(1-4C)alkoxy, R 19 -oxy(1-4C)alkyl, R 19 -oxycarbonyl(1-4C)alkyl, R 20 R 21 -aminosulfonyl, R 20 -oxysulfonyl, aminoiminomethyl, (di)(1-4C)alkylaminoiminomethyl or (2-6C)-heterocycloalkyliminomethyl, trifluoromethylsulfonyl; R 23 -oxycarbonyl, R 23 -carbonyl or R 23 R 24 -aminocarbonyl;

R 8 is H or (1-4C)alkyl;

R 9 is (1-4C)alkylsulfonyl, (1-6C)alkylcarbonyl, (2-6C)alkenylcarbonyl, (2-6C)-alkynylcarbonyl, (3-6C)cycloalkylcarbonyl, (3-6C)cycloalkyl(1-4C)alkylcarbonyl, (1-4C)alkoxycarbonyl, (3-4C)alkenyloxycarbonyl, (3-4C)alkynyloxycarbonyl, (di)(1-4C)alkylaminocarbonyl, (2-6C)heterocycloalkylcarbonyl, (5-8C)alkyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl(1-4C)alkyl, (di)(1-4C)alkylamino(2-4C)alkyl, (2-6C)heterocycloalkyl(2-4C)alkyl or phenylcarbonyl, phenylsulfonyl, phenyl(1-4C)alkoxy(1-4C)alkylcarbonyl, phenyl(1-4C)alkyl, (2-5C)heteroarylcarbonyl, (2-5C)heteroarylsulfonyl, (2-5C)heteroaryl(1-4C)alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (1-4C)alkyl, (1-4C)alkoxy or (di)(1-4C)alkylamino;

R 10 is H or (1-4C)alkyl;

R 11 is hydroxy(2-4C)alkyl, amino(2-4C)alkyl, (1-4C)alkoxy(2-4C)alkyl or (di)-(1-4C)alkylamino(2-4C)alkyl; or

R 10 R 11 in R 10 R 11 -aminocarbonyl may be joined in a (4-6C)heterocycloalkenyl ring or a (2-6C)heterocycloalkyl ring substituted with one or more substituents selected from (1-4C)alkyl, (1-4C)alkoxy(1-4C)alkyl and hydroxy(1-4C)alkyl;

R 12 , R 13 are independently H, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (3-6C)-cycloalkyl, hydroxy(2-4C)alkyl, (1-4C)alkoxy(2-4C)alkyl, (3-6C)cycloalkyl-(1-4C)alkyl, (2-6C)heterocycloalkyl(1-4C)alkyl, amino(2-4C)alkyl, (di)(1-4C)alkylamino(2-4C)alkyl or phenyl(1-4C)alkyl, (2-5C)heteroaryl(1-4C)alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (1-4C)-alkyl, (1-4C)alkoxy and (di)(1-4C)alkylamino; or

R 12 R 13 in R 12 R 13 -amino(1-4C)alkylcarbonylamino may be joined in a (4-6C)-heterocycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (1-4C)alkyl, (1-4C)alkoxy(1-4C)alkyl and hydroxy(1-4C)alkyl;

R 14 , R 15 are independently H, (1-6C)alkyl, (2-6C)heterocycloalkyl(1-4C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl, (1-4C)alkoxy(2-4C)alkyl, hydroxy(2-4C)alkyl, (di)(1-4C)alkylamino(2-4C)alkyl, amino(2-4C)alkyl, (1-4C)alkoxycarbonyl-(1-4C)alkyl, (1-6C)alkylcarbonyl, (3-6C)cycloalkylcarbonyl, (1-4C)alkoxycarbonyl, (3-4C)alkenyloxycarbonyl, (di)(1-4C)alkylaminocarbonyl, (2-6C)heterocycloalkylcarbonyl or (2-5C)heteroaryl(1-4C)alkyl, phenyl(1-4C)alkyl, (2-5C)heteroarylcarbonyl, phenylcarbonyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (1-4C)alkyl or (1-4C)alkoxy, (di)(1-4C)alkylamino; or

R 14 R 15 in R 14 R 15 -amino(1-4C)alkyl may be joined in a (4-6C)heterocycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (1-4C)alkyl, (1-4C)alkoxy(1-4C)alkyl and hydroxy(1-4C)alkyl;

R 16 is (2-6C)heterocycloalkyl(1-4C)alkyl, (di)(1-4C)alkylamino(2-4C)alkyl, (2-4C)alkoxy(1-4C)alkyl, hydroxy(2-4C)alkyl, amino(2-4C)alkyl, hydroxycarbonyl(1-4C)alkyl, (1-4C)alkoxycarbonyl(1-4C)alkyl, (1-4C)alkoxycarbonyl, (3-4C)alkenyloxycarbonyl, (3-4C)alkynyloxycarbonyl, (di)(1-4C)alkylaminocarbonyl, (2-6C)heterocycloalkylcarbonyl, or phenyl(1-4C)alkyl, (2-5C)heteroaryl(1-4C)alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (1-4C)alkyl, (1-4C)alkoxy and (di)(1-4C)alkylamino;

R 17 , R 18 are independently H, (1-6C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl, (1-4C)-alkoxy(2-4C)alkyl, hydroxy(2-4C)alkyl, amino(2-4C)alkyl, (di)(1-4C)alkylamino(2-4C)alkyl, (2-6C)heterocycloalkyl(2-4C)alkyl, or phenyl(1-4C)alkyl, (2-5C)heteroaryl(1-4C)alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (1-4C)alkyl, (1-4C)alkoxy and (di)(1-4C)alkylamino; or

R 17 R 18 in R 17 R 18 -aminocarbonyl(1-4C)alkoxy may be joined in a (4-6C)hetero-cycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (1-4C)alkyl, (1-4C)alkoxy(1-4C)alkyl and hydroxy(1-4C)alkyl;

R 19 is H or (1-6C)alkyl;

R 20 , R 21 are independently H, (1-6C)alkyl, (1-6C)alkenyl, (1-6C)alkynyl or (1-4C)-alkoxy(1-4C)alkyl; or

R 20 R 21 in R 20 R 21 -aminosulfonyl may be joined in a (4-6C)heterocycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (1-4C)alkyl, (1-4C)alkoxy(1-4C)alkyl and hydroxy-(1-4C)alkyl;

X is O or N—R 22 ;

Y is CH 2 , C(O) or SO 2 ;

Z is CN or NO 2 ;

R 22 is H, (1-4C)alkyl;

R 23 , R 24 are independently H, (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (3-6C)-cycloalkyl, (3-6C)cycloalkyl(1-4C)alkyl, (2-6C)heterocycloalkyl, (2-6C)heterocycloalkyl(1-4C)alkyl, (1-4C)alkoxycarbonyl(1-4C)alkyl, (di)(1-4C)alkylaminocarbonyl(1-4C)alkyl or phenylaminocarbonyl(1-4C)alkyl, (2-5C)heteroarylaminocarbonyl(1-4C)alkyl, phenyl, (2-5C)heteroaryl, phenyl(1-4C)alkyl, (2-5C)heteroaryl(1-4C)alkyl, optionally substituted at the (hetero)atom with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkoxy and (di)(1-4C)-alkylamino; or

R 23 R 24 in R 23 R 24 -aminocarbonyl may be joined in a (4-6C)heterocycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (1-4C)alkyl, (1-4C)alkoxy(1-4C)alkyl and hydroxy-(1-4C)alkyl; with the proviso that the compounds of formula I wherein X is O, R 4 is phenyl and R 7 is selected from H, (1-4C)alkylthio, (1-4C)alkylsulfonyl, di(1-4C)alkylamino, R 23 -oxycarbonyl, R 23 -carbonyl and R 23 R 24 -aminocarbonyl, and the compounds of formula I wherein X is O, R 4 is (2-5C)heteroaryl and R 7 is H or (di)(1-4C)-alkylamino, are excluded.

2. The 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to claim 1 wherein R 1 is (1-6C)alkyl.

3. The 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to claim 1 wherein R 2 is halogen.

4. The 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to claim 1 wherein R 3 is (1-4C)alkoxy.

5. The 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to claim 1 wherein Z is CN.

6. The 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to claim 1 wherein X is O.

7. The 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to claim 1 wherein Y is CH 2 .

8. The 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to claim 1 wherein R 7 is R 8 R 9 -amino, R 10 R 11 -aminocarbonyl, R 12 R 13 -amino-(1-4C)alkylcarbonylamino, R 14 R 15 -amino(1-4C)alkyl or R 17 R 18 -aminocarbonyl(1-4C)alkoxy.

9. The 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to claim 1 wherein

R 8 is H;

R 9 is (1-4C)alkylsulfonyl, (1-6C)alkylcarbonyl, (3-6C)cycloalkylcarbonyl, (1-4C)alkoxycarbonyl, (3-4C)alkenyloxycarbonyl, (di)(1-4C)alkylaminocarbonyl, (2-6C)heterocycloalkylcarbonyl, or phenylcarbonyl, phenyl(1-4C)alkoxy(1-4C)alkylcarbonyl, (2-5C)heteroarylcarbonyl, (2-5C)heteroarylsulfonyl or (2-5C)heteroaryl(1-4C)alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from, halogen or (1-4C)alkoxy;

R 10 is H or (1-4C)alkyl;

R 11 is hydroxy(2-4C)alkyl, amino(2-4C)alkyl, (1-4C)alkoxy(2-4C)alkyl or (di)-(1-4C)alkylamino(2-4C)alkyl; or

R 10 R 11 in R 10 R 11 -aminocarbonyl may be joined in a (4-6C)heterocycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (1-4C)alkyl;

R 12 , R 13 are independently H, (1-6C)alkyl, (3-6C)cycloalkyl, hydroxy(2-4C)alkyl, (1-4C)alkoxy(2-4C)alkyl, (2-6C)heterocycloalkyl(1-4C)alkyl or (di)-(1-4C)alkylamino(2-4C)alkyl or phenyl(1-4C)alkyl or (2-5C)heteroaryl(1-4C)alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from halogen; or

R 12 R 13 in R 12 R 13 -amino(1-4C)alkylcarbonylamino may be joined in a (4-6C)-heterocycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (1-4C)alkyl or hydroxy(1-4C)alkyl; R 14 , R 15 are independently H, (1-6C)alkyl, hydroxy(2-4C)alkyl, (1-4C)alkoxycarbonyl(1-4C)alkyl, (1-6C)alkylcarbonyl, (3-6C)cycloalkylcarbonyl, (1-4C)alkoxycarbonyl, (2-5C)heteroaryl(1-4C)alkyl, (2-5C)heteroarylcarbonyl or phenylcarbonyl;

R 16 is (2-6C)heterocycloalkyl(1-4C)alkyl, (di)(1-4C)alkylamino(2-4C)alkyl, (2-4C)alkoxy(1-4C)alkyl, hydroxycarbonyl(1-4C)alkyl, (1-4C)alkoxycarbonyl-(1-4C)alkyl; or phenyl(1-4C)alkyl or (2-5C)heteroaryl(1-4C)alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from halogen or (1-4C)alkoxy;

R 17 , R 18 are independently H, (1-6C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl, (1-4C)-alkoxy(2-4C)alkyl or (2-6C)heterocycloalkyl(2-4C)alkyl; or phenyl(1-4C)alkyl or (2-5C)heteroaryl(1-4C)alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from halogen; or

R 17 R 18 in R 17 R 18 -aminocarbonyl(1-4C)alkoxy may be joined in a (4-6C)hetero-cycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (1-4C)alkyl or hydroxy(1-4C)alkyl.

10. The 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to claim 8 wherein R 7 is R 8 R 9 -amino.

11. The 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to claim 10 wherein R 8 is H and R 9 is (1-4C)alkylsulfonyl.

12. The 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative or a pharmaceutically acceptable salt thereof according to claim 1 selected from the group of

N-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-3,4,5-trimethoxy-benzamide;

N-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-2-[(pyridin-4-ylmethyl)-amino]-acetamide;

N-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-2-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-acetamide;

4-{3-Bromo-4-[3-(3,6-dihydro-2H-pyridine-1-carbonyl)-benzyloxy]-5-ethoxy-phenyl}-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile;

3-[Bis-(2-methoxy-ethyl)-amino]-N-{3-[2-bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-propionamide;

2-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenoxy}-N,N-dimethyl-acetamide;

4-{3-Bromo-5-ethoxy-4-[3-(2-morpholin-4-yl-2-oxo-ethoxy)-benzyloxy]-phenyl}-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile;

Furan-2-carboxylic acid {2-[2-bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-amide;

N-{2-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-acrylamide;

Cyclopropanecarboxylic acid {2-[2-bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-amide;

2-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-carbamic acid methyl ester;

1-{2-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-3-methyl-urea

{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-pyridin-2-yl}-carbamic acid methyl ester

4-(3-Bromo-5-ethoxy-4-{3-[(1H-imidazol-4-ylmethyl)-amino]-benzyloxy}-phenyl)-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile;

N-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-methanesulfonamide;

{4-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-carbamic acid allyl ester;

4-[3-Bromo-5-ethoxy-4-(1-methanesulfonyl-1H-pyrrol-2-ylmethoxy)-phenyl]-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile;

4-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-N-methyl-benzamidine;

4-{3-Bromo-5-ethoxy-4-[(pyridin-3-ylmethyl)-amino]-phenyl}-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile;

N-(2-{[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenylamino]-methyl}-phenyl)-methanesulfonamide;

4-{3-Bromo-4-[2-(cyclopropylmethyl-amino)-benzyloxy]-5-ethoxy-phenyl}-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile; or

N-{2-[2-Bromo-4-((4R,7S)-3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-4,5-difluoro-phenyl}-methanesulfonamide.

13. A pharmaceutical composition comprising a 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative or a pharmaceutically acceptable salt thereof according to claim 1 , and pharmaceutically suitable auxiliaries.

14. The pharmaceutical composition of claim 13 wherein the 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative is selected from

N-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-3,4,5-trimethoxy-benzamide;

N-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propy 1 -1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-2-[(pyridin-4-ylmethyl)-amino]-acetamide;

N-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-2-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-acetamide;

4-{3-Bromo-4-[3-(3,6-dihydro-2H-pyridine-1-carbonyl)-benzyloxy]-5-ethoxy-phenyl}-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile;

3-[Bis-(2-methoxy-ethyl)-amino]-N-{3-[2-bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-propionamide;

2-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenoxy}-N,N-dimethyl-acetamide;

4-{3-Bromo-5-ethoxy-4-[3-(2-morpholin-4-yl-2-oxo-ethoxy)-benzyloxy]-phenyl}-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile;

Furan-2-carboxylic acid {2-[2-bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-amide;

N-{2-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-acrylamide;

Cyclopropanecarboxylic acid {2-[2-bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-amide;

2-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-carbamic acid methyl ester;

1-{2-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-3-methyl-urea

{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-pyridin-2-yl}-carbamic acid methyl ester

4-(3-Bromo-5-ethoxy-4-{3-[(1H-imidazol-4-ylmethyl)-amino]-benzyloxy}-phenyl)-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile;

N-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-methanesulfonamide;

{4-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-carbamic acid allyl ester;

4-[3-Bromo-5-ethoxy-4-(1-methanesulfonyl-1H-pyrrol-2-ylmethoxy)-phenyl]-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile;

4-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-N-methyl-benzamidine;

4-{3-Bromo-5-ethoxy-4-[(pyridin-3-ylmethyl)-amino]-phenyl}-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile;

N-(2-{[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenylamino]-methyl}-phenyl)-methanesulfonamide;

4-{3-Bromo-4-[2-(cyclopropylmethyl-amino)-benzyloxy]-5-ethoxy-phenyl}-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile; or

N-{2-[2-Bromo-4-((4R,7S)-3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-4,5-difluoro-phenyl}-methanesulfonamide, or a pharmaceutically acceptable salt thereof.

Assignments (4)
MERGER Recorded Mar 8, 2013
From: ORGANON BIOSCIENCES NEDERLAND B.V.
To: MERCK SHARP & DOHME B.V.
Reel/Frame 029940/0296 →
MERGER Recorded Mar 7, 2013
From: MSD OSS B.V.
To: ORGANON BIOSCIENCES NEDERLAND B.V.
Reel/Frame 029939/0001 →
MERGER Recorded Dec 1, 2011
From: N.V. ORGANON
To: MSD OSS B.V.
Reel/Frame 027307/0482 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 26, 2007
From: GRIMA POVEDA, PEDRO MANUEL; KARSTENS, WILLEM FREDERIK JOHAN; TIMMERS, CORNELIS MARIUS
To: N.V. ORGANON
Reel/Frame 020154/0195 →