Bicyclic derivatives

Patent metadata

Field	Value
Publication number	US-10669268-B2
Application number	US-201715583679-A
Country	US
Kind code	B2
Filing date	May 1, 2017
Priority date	Sep 25, 2012
Publication date	Jun 2, 2020
Grant date	Jun 2, 2020

Abstract

The invention provides novel compounds having the general formula (I)

wherein R 1 , Y, A, W, R 2 , m, n, p and q are as described herein, compositions including the compounds and methods of using the compounds.

First claim

The invention claimed is:

1. A compound of formula (I)

wherein
R 1 is alkyl, haloalkyl, substituted cycloalkyl, substituted cycloalkylalkyl, substituted piperazinyl, substituted piperidinyl, substituted indanyloxyalkyl, substituted phenyl, substituted phenyl alkyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted phenylalkenyl, substituted phenylalkynyl, substituted pyridinyl, substituted pyridinylalkyl, substituted pyridinylalkenyl, substituted pyridinylalkynyl substituted thiophenyl, substituted thiophenylalkyl, substituted thiophenylalkenyl, substituted thiophenylalkynyl, naphthyl, substituted naphthyl, quinolyl, substituted quinolinyl, isoquinolyl, substituted isoquinolinyl, substituted 2,3-dihydro-1H-isoindol-2-yl, substituted 1H-indol-2-yl, or substituted benzofuran-2-yl, wherein substituted cycloalkyl, substituted cycloalkylalkyl, substituted piperazinyl, substituted piperidinyl, substituted indanyloxyalkyl, substituted phenyl, substituted phenyl alkyl, substituted phenylalkynyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted phenylalkenyl, substituted pyridinyl, substituted pyridinyl alkyl, substituted pyridinylalkenyl, substituted pyridinylalkynyl, substituted thiophenyl, substituted thiophenylalkyl, substituted thiophenylalkenyl, substituted thiophenylalkynyl, substituted naphthyl, substituted quinolinyl, substituted isoquinolinyl, substituted 2,3-dihydro-1H-isoindol-2-yl, substituted 1H-indol-2-yl, and substituted benzofuran-2-yl are substituted with R 8 , R 9 , and R 10 ;

Y is -OC(O)-, -NR 7 C(O)-, -C(O)-, -S(O) 2 -,
A is -N- or CR 5 -;
W is -O-, -S-, -NR 6 -, -C(O)-, -S(O) 2 -, -C(O)-NR 6 -, or -CR 3 R 4 -;
R 3 and R 4 are independently selected from H, halogen, alkyl, and cycloalkyl;
R 5 , R 6 , and R 7 are independently selected from H, alkyl, and cycloalkyl;
R 8 , R 9 , and R 10 are independently selected from H, alkyl, hydroxyalkyl, haloalkyl, hydroxyhaloalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkoxy, cycloalkoxy, cycloalkoxyalkyl, cycloalkylalkoxyalkyl, alkoxy, alkoxyalkyl, haloalkoxy, alkoxyhaloalkyl, alkoxyalkoxy, alkoxyalkoxyalkyl, phenyl, substituted phenyl, pyridinyl, substituted pyridinyl, pyrrolyl, substituted pyrrolyl, pyrrolidinyl, substituted pyrrolidinyl, tetrahydrofuranyl, substituted tetrahydrofuranyl, halogen, hydroxy, cyano, alkylsulfanyl, haloalkylsulfanyl, cycloalkylsulfanyl, alkylsulfinyl, haloalkylsulfinyl, cycloalkylsulfinyl, alkylcarbonyl, haloalkylcarbonyl, cycloalkylcarbonyl, alkyl sulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, substituted aminosulfonyl, substituted amino and substituted aminoalkyl, wherein substituted aminosulfonyl, substituted amino, and substituted aminoalkyl are substituted on the nitrogen atom with one to two sub stituents independently selected from H, alkyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, and cycloalkylcarbonyl, and wherein substituted phenyl, substituted pyrrolyl, substituted pyrrolidinyl, substituted tetrahydrofuranyl, and substituted pyridinyl are substituted with one to three substituents independently selected from alkyl, halogen, haloalkyl, alkoxy, and haloalkoxy;
m, n, p, and q are independently selected from 1 and 2; and
R 2 is

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 , wherein
R 1 is alkyl, haloalkyl, substituted cycloalkyl, substituted cycloalkylalkyl, substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenyl cycloalkyl, substituted phenyl alkenyl, substituted phenylalkynyl, substituted pyridinyl, substituted pyridinylalkyl, substituted pyridinylalkenyl, substituted pyridinylalkynyl, substituted thiophenyl, substituted thiophenyl alkyl, substituted thiophenylalkenyl, substituted thiophenylalkynyl, substituted 2,3-dihydro-1H-isoindol-2-yl, substituted 1H-indol-2-yl, or substituted benzofuran-2-yl, wherein substituted cycloalkyl, substituted cycloalkylalkyl, substituted phenyl, substituted phenylalkyl, substituted phenylalkynyl, substituted phenoxyalkyl, substituted phenyl cycl oalkyl, substituted phenylalkenyl, substituted pyridinyl, substituted pyridinylalkyl, substituted pyridinylalkenyl, substituted pyridinylalkynyl, substituted thiophenyl, substituted thiophenylalkyl, substituted thiophenylalkenyl, substituted thiophenylalkynyl, substituted 2,3-dihydro-1H-isoindol-2-yl, substituted 1H-indol-2-yl, and substituted benzofuran-2-yl are substituted with R 8 , R 9 , and R 10 ;

Y is -OC(O)-, -NR 7 C(O)-, -C(O)-, -S(O) 2 -,
A is -N- or CR 5 -;
W is -O-, -S-, -NR 6 -, -C(O)-, -S(O) 2 -, -C(O)-NR 6 -, or -CR 3 R 4 -;
R 3 and R 4 are independently selected from H, halogen, alkyl, and cycloalkyl;
R 5 , R 6 and R 7 are independently selected from H, alkyl, and cycloalkyl;
R 8 , R 9 and R 10 are independently selected from H, alkyl, hydroxyalkyl, haloalkyl, hydroxyhaloalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkoxy, cycloalkoxy, cycloalkoxyalkyl, cycloalkylalkoxyalkyl, alkoxy, alkoxyalkyl, haloalkoxy, alkoxyhaloalkyl, alkoxyalkoxy, alkoxyalkoxyalkyl, phenyl, substituted phenyl, pyridinyl, substituted pyridinyl, halogen, hydroxy, cyano, alkylsulfanyl, haloalkylsulfanyl, cycloalkylsulfanyl, alkyl sulfinyl, haloalkylsulfinyl, cycloalkylsulfinyl, alkyl sulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, substituted aminosulfonyl, substituted amino and substituted aminoalkyl, wherein substituted aminosulfonyl, substituted amino, and substituted aminoalkyl are substituted on the nitrogen atom with one to two sub stituents independently selected from H, alkyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, and cycloalkylcarbonyl, and wherein substituted phenyl and substituted pyridinyl are optionally substituted with one to three substituents independently selected from alkyl, halogen, haloalkyl, alkoxy, and haloalkoxy;
m, n, p, and q are independently selected from 1 and 2; and
R 2 is

or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is substituted cycloalkylalkyl, substituted piperazinyl, substituted piperidinyl, substituted indanyloxyalkyl, substituted phenyl, substituted phenyl alkyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted phenyl alkenyl, substituted pyridinyl alkyl, substituted pyridinylalkenyl, naphthyl, substituted naphthyl, substituted quinolinyl, substituted isoquinolinyl, or substituted 1H-indol-2-yl, wherein substituted cycloalkyl alkyl, substituted piperazinyl, substituted piperidinyl, substituted indanyloxyalkyl, substituted phenyl, substituted phenyl alkyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted phenylalkenyl, substituted pyridinylalkyl, substituted pyridinylalkenyl, substituted naphthyl, substituted quinolinyl, substituted isoquinolinyl, and substituted 1H-indol-2-yl are substituted with R 8 , R 9 , and R 10 .

4. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is substituted cycloalkylalkyl, substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted

Assignees

• Hoffmann La Roche

Inventors

• Hert Jerome
• Hunziker Daniel
• Mattei Patrizio
• Mauser Harald
• Tang Guozhi
• Wang Lisha

Classifications

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07D519/00

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title