IP Library Granted Patent US 9,790,200
Granted Patent B2
US 9,790,200 · App. 15/498,957 · Granted Oct 17, 2017

Dihydroquinoline pyrazolyl compounds

Inventors: Johannes Aebi (Binningen, CH); Kurt Amrein (Itingen, CH); Benoit Hornsperger (Altkirch, FR); Bernd Kuhn (Reinach BL, CH); Hans P. Maerki (Basel, CH); Rainer E. Martin (Basel, CH); Alexander V. Mayweg (Basel, CH); Xuefei Tan (Shanghai, CN)
Assignee: Hoffmann-La Roche Inc.
C07D401/04C07D401/14
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Quick Facts
Patent No.
US 9,790,200
App. No.
15/498,957
Granted
Oct 17, 2017
Kind
B2
Abstract

The invention provides novel compounds having the general formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 15 , R 16 , R 17 and n are as described herein, compositions including the compounds and methods of using the compounds.

Claims (46)

1. A compound of formula (I)

wherein

R 1 , R 5 , R 6 , R 7 and R 8 are independently selected from H, alkyl, haloalkyl, cycloalkyl or halocycloalkyl;

R 2 , R 3 and R 4 are independently selected from H, halogen, alkyl, haloalkyl, cycloalkyl or halocycloalkyl;

R 9 is alkylsulfanylalkyl, alkylsulfonylalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, hetroarylalkyl, substituted heteroarylalkyl or the group A, wherein substituted aryl, substituted arylalkyl, substituted heteroaryl and substituted heteroarylalkyl are substituted with one to three substituents selected from the group consisting of alkyl, halogen, haloalkyl, cycloalkyl, halocycloalkyl, cyano, alkoxy, haloalkoxy, alkylsulfanyl, haloalkylsulfanyl, alkylsulfonyl and haloalkylsulfonyl;

R 10 is pyrazolyl, substituted pyrazolyl, pyridinyl or substituted pyridinyl, wherein substituted pyrazolyl and substituted pyridinyl are substituted with one to three substituents selected from the group consisting of alkyl, halogen, haloalkyl, cycloalkyl and halocycloalkyl;

R 15 is H, alkyl, haloalkyl, cycloalkyl or halocycloalkyl;

R 16 and R 17 are independently selected from H, alkyl and cycloalkyl;

n is zero or 1;

or, pharmaceutically acceptable salts thereof.

2. The compound according to claim 1 , wherein R 1 is alkyl.

3. The compound according to claim 1 , wherein R 5 , R 6 , R 7 and R 8 are H.

4. The compound according to claim 1 wherein R 2 and R 3 are H.

5. The compound according to claim 1 wherein R 4 is H or halogen.

6. The compound according to claim 1 , wherein R 4 is H.

7. The compound according to claim 1 wherein R 15 is H.

8. The compound according to claim 1 , wherein R 16 and R 17 are H.

9. The compound according to claim 1 wherein n is 0.

10. The compound according to claim 1 wherein R 1 is alkyl, R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 15 , R 16 and R 17 are H, R 4 is H or halogen and n is 0.

11. The compound according to claim 10 , wherein R 9 is alkylsulfanylalkyl, alkylsulfonylalkyl, substituted aryl, substituted arylalkyl or the group A, wherein substituted aryl and substituted arylalkyl are substituted with one to three substituents selected from alkyl, halogen, cyano, alkoxy, alkylsulfanyl and alkylsulfonyl.

12. The compound according to claim 1 , wherein R 9 is alkylsulfanylalkyl, alkylsulfonylalkyl, substituted aryl, substituted arylalkyl or the group A, wherein substituted aryl and substituted arylalkyl are substituted with one to three substituents selected from alkyl, halogen, cyano, alkoxy, alkylsulfanyl and alkylsulfonyl.

13. The compound according to claim 1 wherein R 10 is either pyrazolyl substituted by one alkyl or pyridinyl substituted by one halogen.

14. The compound of claim 11 wherein R 9 is the group A and R 10 is either pyrazolyl substituted by one alkyl or pyridinyl substituted by one halogen.

15. The compound according to claim 1 wherein R 9 is aryl substituted with one to three substituents selected from alkyl, halogen, cyano, alkoxy, alkylsulfanyl and alkylsulfonyl.

16. The compound according to claim 11 wherein R 9 is aryl substituted with one to three substituents selected from alkyl, halogen, cyano, alkoxy, alkylsulfanyl and alkylsulfonyl.

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

4-[[5-(1-Methyl-2-oxo-3,4-dihydroquinolin-6-yl)-1H-pyrazol-4-yl]oxy]benzonitrile;

6-[4-(4-Chlorophenoxy)-1H-pyrazol-5-yl]-1-methyl-3,4-dihydroquinolin-2-one;

3-Methoxy-4-[[5-(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)-1H-pyrazol-4-yl]oxy]benzonitrile;

3-Chloro-4-[[5-(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)-1H-pyrazol-4-yl]oxy]benzonitrile;

2-Fluoro-4-[[5-(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)-1H-pyrazol-4-yl]oxy]benzonitrile;

2-Chloro-4-[[5-(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)-1H-pyrazol-4-yl]oxy]benzonitrile;

6-[4-(3-Chlorophenoxy)-1H-pyrazol-5-yl]-1-methyl-3,4-dihydroquinolin-2-one;

1-Methyl-6-[4-(4-methylsulfanylphenoxy)-1H-pyrazol-5-yl]-3,4-dihydroquinolin-2-one;

1-Methyl-6-[4-(3-methylsulfanylphenoxy)-1H-pyrazol-5-yl]-3,4-dihydroquinolin-2-one;

1-Methyl-6-[4-(3-methylsulfonylphenoxy)-1H-pyrazol-5-yl]-3,4-dihydroquinolin-2-one;

1-Methyl-6-[4-(4-methylsulfonylphenoxy)-1H-pyrazol-5-yl]-3,4-dihydroquinolin-2-one;

1-Methyl-6-[4-(2-methylsulfanylethoxymethyl)-1H-pyrazol-3-yl]-3,4-dihydroquinolin-2-one;

(rac)-1-Methyl-6-[4-(1-methylsulfanylpropan-2-yloxymethyl)-1H-pyrazol-3-yl]-3,4-dihydroquinolin-2-one;

1-Methyl-6-[4-(2-methylsulfonylethoxymethyl)-1H-pyrazol-3-yl]-3,4-dihydroquinolin-2-one;

6-[4-[(4-Methoxyphenyl)methoxy]-1H-pyrazol-3-yl]-1-methyl-3,4-dihydroquinolin-2-one;

6-[4-[[1-(3-Chloropyridine-2-carbonyl)azetidin-3-yl]oxymethyl]-1H-pyrazol-3-yl]-5-fluoro-1-methyl-3,4-dihydroquinolin-2-one; and,

5-Fluoro-1-methyl-6-[4-[[1-(1-methylpyrazole-4-carbonyl)azetidin-3-yl]oxymethyl]-1H-pyrazol-3-yl]-3,4-dihydroquinolin-2-one; or,

a pharmaceutically acceptable salt thereof.

18. A process to prepare a compound according to to claim 1 comprising the reaction of a compound of formula (II) in the presence of hydrazine hydrate;

19. A pharmaceutical composition comprising a compound according to claim 1 and at least one pharmaceutically acceptable carrier, diluent or excipient.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 20, 2025
From: HOFFMANN-LA ROCHE INC.
To: CINCOR PHARMA, INC.
Reel/Frame 071166/0614 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 31, 2017
From: AEBI, JOHANNES; AMREIN, KURT; HORNSPERGER, BENOIT; KUHN, BERND; MAERKI, HANS P.; MARTIN, RAINER E.; MAYWEG, ALEXANDER V.
To: F. HOFFMANN-LA ROCHE AG
Reel/Frame 043467/0343 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 31, 2017
From: TAN, XUEFEI
To: ROCHE R&D CENTER (CHINA) LTD
Reel/Frame 043467/0354 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 31, 2017
From: ROCHE R&D CENTER (CHINA) LTD
To: F. HOFFMANN-LA ROCHE AG
Reel/Frame 043467/0360 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 31, 2017
From: F. HOFFMANN-LA ROCHE AG
To: HOFFMANN-LA ROCHE INC.
Reel/Frame 043467/0367 →
Continuity (2)
Continuation PCTEP2015074774 · Oct 26, 2015
Related Publication 20170226079A1 · Aug 10, 2017