Granted Patent B2

US 12,258,323 · App. 17/862,255 · Granted Mar 25, 2025

Inventors: Manuel Ellermann (Berlin, DE); Stefan Nikolaus Gradl (Berlin, DE); Charlotte Christine Kopitz (Falkenesee, DE); Martin Lange (Berlin, DE); Adrian Tersteegen (Wuppertal, DE); Philip Lienau (Berlin, DE); Christa Hegele-Hartung (Mülheim an der Ruhr, DE); Detlev Sülzle (Berlin, DE); Timothy A. Lewis (Cambridge, MA); Heidi Greulich (Cambridge, MA); Xiaoyun Wu (Cambridge, MA); Matthew Meyerson (Boston, MA); Alex Burgin (Cambridge, MA)

Assignees: Bayer Aktiengesellschaft; Bayer Pharma Aktiengesellschaft; The Broad Institute, Inc.; Dana-Farber Cancer Institute, Inc.

C07D273/04C07D413/10C07D413/12C07D417/10C07D471/04C07D491/107C07D495/10

Abstract

Claims (617)

1. A compound of formula (I)

where

R 1 is selected from a hydrogen atom, a halogen atom, a cyano group, a C 1 -C 3 -alkyl group, a C 1 -C 3 -haloalkyl group, and a C 1 -C 3 -haloalkoxy group;

R 2 is selected from a hydrogen atom and a halogen atom;

R 3 is selected from,

a C 1 -C 6 -alkyl group which is substituted with one or two substituents and each substituent is independently selected from a hydroxy group, a C 1 -C 4 -alkoxy group and a 3-to 7-membered heterocycloalkyl group;

a C 2 -C 6 -alkenyl group which is optionally substituted with an C 1 -C 4 -alkoxy group;

a C 3 -C 9 -cycloalkyl group, which is optionally substituted with a hydroxy group;

a C 5 -C 9 -cycloalkenyl group, which is optionally substituted with a hydroxy group;

a 3- to 9-membered heterocycloalkyl group, comprising one, two or three heteroatoms which are independently selected from —O—, —S—, —S(O)—, S(O) 2 , and —NR 9 —,

and said heterocycloalkyl group optionally further comprising a bridging group selected from —O—, —NR 9 —, —CH 2 —, —CH 2 —CH 2 —, —O—CH 2 —, —CH 2 —O—, —NR 9 —CH 2 —, and —CH 2 —NR 9 —;

and said heterocycloalkyl group is optionally substituted with one, two or three substituents and each substituent is independently selected from

a halogen atom;

a oxo (═O) group;

a cyano group;

a hydroxy group;

a C 1 -C 3 -alkyl group which is optionally further substituted with a hydroxy group;

a C 1 -C 3 -haloalkyl group;

a C 1 -C 3 -alkoxy group;

a C 1 -C 3 -haloalkoxy group;

a C(O)NR 5 R 6 group

and a NR 5 R 6 group;

a 5- to 9-membered heterocycloalkyl group which is partially unsaturated and optionally substituted with one, two or three substituents and each substituent is independently selected from an oxo group (═O), a C 1 -C 3 -alkyl group, a —C(O)R 5 R 6 group and a halogen atom;

an aryl group which is optionally substituted with one, two, three or four substituents and each substituent is independently selected from a halogen atom, a hydroxy group, a cyano group, a C 1 -C 3 -alkyl group, a C 1 -C 3 -haloalkyl group, a C 1 -C 3 -alkoxy group, a C 1 -C 3 -haloalkoxy group, and a NR 5 R 6 group;

a mono- or bicyclic heteroaryl group which is optionally substituted with one, two or three substituents and each substituent is independently selected from a halogen atom, a C 1 -C 3 -alkyl group, a cyano group, a C 1 -C 3 -haloalkyl group, a C 1 -C 3 -hydroxalkyl group, a C 1 -C 3 -alkoxy group, a hydroxy group, and a NR 5 R 6 group, with the proviso that said monocyclic heteroaryl group is not 4-pyridyl;

and a NR 7 R 8 group;

R 4 is selected from a hydrogen atom, and a C 1 -C 3 -alkyl group;

R 5 /R 6 are independently selected from a hydrogen atom, a C 1 -C 6 -alkyl group, a —C 1 -C 5 -alkylene-O—C 1 -C 5 -alkyl group, a —C 1 -C 5 -alkylene-S—C 1 -C 5 -alkyl group, C 3 -C 6 -cycloalkyl group, and a C 3 -C 5 -heterocycloalkyl group;

R 7 /R 8 are independently selected from a hydrogen atom, with the proviso that R 7 =R 8 =hydrogen is excluded,

a C 1 -C 6 -alkyl group,

which is substituted with one, two, three or four substituents and said substituent is independently selected from

a halogen atom,

a cyano group,

a hydroxy group,

a C(O)NR 5 R 6 group,

a NR 5 R 6 group,

a C 1 -C 3 -alkoxy group,

a C 3 -C 7 -cycloalkyl group which is optionally substituted with one or two substituents and said substituents are independently selected from a C 1 -C 3 -alkyl group, a oxo (═O) group, a hydroxy group, and a C 1 -C 3 -hydroxyalkyl group;

a 3- to 7-membered heterocycloalkyl group which itself is optionally substituted with, a C 1 -C 3 -alkyl group or an oxo (═O) group;

a heteroaryl group, which itself is optionally substituted with a C 1 -C 3 -alkyl group;

a —C 1 -C 5 -alkylene-O—C 1 -C 5 -alkyl group;

a —C 1 -C 5 -alkylene-S—C 1 -C 5 -alkyl group;

a —C 1 -C 5 -alkylene-NR 5 -C 1 -C 5 -alkyl group;

a C 3 -C 6 -cycloalkyl group which is optionally substituted with a hydroxy group; and

a 3- to 6-membered heterocycloalkyl group, which is optionally substituted with one or two substituents, said substituent independently selected from C 1 -C 3 -alkyl group and a hydroxy group;

R 9 is a hydrogen atom or a C 1 -C 3 -alkyl group or a bond;

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

2. The compound according to claim 1 ,

where

R 1 is selected from a hydrogen atom, a halogen atom, a cyano group, a C 1 -C 3 -alkyl group, a C 1 -C 3 -haloalkyl group, and a C 1 -C 3 -haloalkoxy group;

R 2 is selected from a hydrogen atom and a halogen atom;

R 3 is selected from

a C 1 -C 6 -alkyl group which is substituted with a substituent which is selected from a hydroxy group, a C 1 -C 4 -alkoxy group, and a 3- to 7-membered heterocycloalkyl group;

a C 2 -C 6 -alkenyl group which is optionally substituted with an C 1 -C 4 -alkoxy group;

a C 3 -C 7 -cycloalkyl group, which is optionally substituted with a hydroxy group;

a C 5 -C 7 -cycloalkenyl group, which is optionally substituted with a hydroxy group;

a 3- to 7-membered-heterocycloalkyl group, comprising one, or two heteroatoms which are independently selected from —O—, S(O) 2 , and —NR 9 —,

and said heterocycloalkyl group is optionally substituted with one, or two substituents and each substituent is independently selected from

a halogen atom;

a cyano group;

a hydroxy group;

a C 1 -C 3 -alkyl group which is optionally further substituted with a hydroxy group;

a C 1 -C 3 -alkoxy group;

a C(O)NR 5 R 6 group and

a NR 5 R 6 group;

a 5- to 7-membered-heterocycloalkyl group, comprising a heteroatom which is selected from —O—, —S— and —NR 9 —, which is partially unsaturated and optionally substituted with a substituent which is selected from a C 1 -C 3 -alkyl group and a halogen atom;

an aryl group which is optionally substituted with one, two, or three substituents and each substituent is independently selected from a halogen atom, a hydroxy group, a cyano group, a C 1 -C 3 -alkyl group, a C 1 -C 3 -haloalkyl group, a C 1 -C 3 -alkoxy group, and a NR 5 R 6 group;

a mono- or bicyclic heteroaryl group which is optionally substituted with a substituent which is selected from a halogen atom, a C 1 -C 3 -alkyl group, a cyano group, a C 1 -C 3 -haloalkyl group, a C 1 -C 3 -alkoxy group, and a NR 5 R 6 group, with the proviso that said monocyclic heteroaryl group is not a pyridin-4-yl group;

and a NR 7 R 8 group;

R 4 is selected from a hydrogen atom, and a C 1 -C 3 -alkyl group;

R 5 /R 6 are independently selected from a hydrogen atom and a C 1 -C 6 -alkyl group;

R 7 /R 8 are independently selected from

a hydrogen atom, with the proviso that R 7 =R 8 =hydrogen is excluded,

a C 1 -C 6 -alkyl group, which is substituted with one, two, three or four substituents and said substituent is independently selected from

a halogen atom;

a cyano group;

a hydroxy group;

a C(O)NR 5 R 6 group;

a NR 5 R 6 group;

a C 1 -C 3 -alkoxy group;

a C 3 -C 7 -cycloalkyl group which is optionally further substituted with one or two substituents and said substituents are independently selected from a C 1 -C 3 -alkyl group, a oxo (═O) group, a hydroxy group, and a C 1 -C 3 -hydroxyalkyl group;

a 3- to 7-membered heterocycloalkyl group, comprising one, two or three heteroatoms which are independently selected from —O— and —NR 9 —, which is optionally further substituted with a C 1 -C 3 -alkyl group;

a heteroaryl group, which is optionally further substituted with a C 1 -C 3 -alkyl group;

a C 3 -C 7 -cycloalkyl group which is optionally substituted with a hydroxy group, or a C 1 -C 3 -alkyl group and

a 3- to 6-membered heterocycloalkyl group, which is optionally substituted with one or two substituents, said substituent independently selected from C 1 -C 3 -alkyl group and a hydroxy group;

R 9 is a hydrogen atom or a C 1 -C 3 -alkyl group or a bond;

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

3. The compound according to claim 1 ,

where

R 1 is selected from a hydrogen atom, a halogen atom, a C 1 -C 3 -alkyl group, a C 1 -C 3 -haloalkyl group, and a C 1 -C 3 -haloalkoxy group;

R 2 is selected from a hydrogen atom and a halogen atom;

R 3 is selected from,

a C 1 -C 6 -alkyl group which is optionally substituted with a substituent which is selected from a hydroxy group, a C 1 -C 4 -alkoxy group, and a 3- to 7-membered heterocycloalkyl group;

a C 2 -C 6 -alkenyl group which is optionally substituted with an C 1 -C 4 -alkoxy group;

a C 3 -C 7 -cycloalkyl group, which is optionally substituted with a hydroxy group;

a C 5 -C 7 -cycloalkenyl group;

a 3- to 7-membered heterocycloalkyl group, comprising one, or two heteroatoms which are independently selected from —O—, and —NR 9 —,

and said heterocycloalkyl group is optionally further substituted with one, or two substituents and each substituent is independently selected from

a halogen atom;

a cyano group;

a hydroxy group;

a C 1 -C 3 -alkyl group which is optionally further substituted with a hydroxy group;

a C 1 -C 3 -alkoxy group and

a C(O)NR 5 R 6 group;

a 5- to 7-membered-heterocycloalkyl group, comprising a heteroatom which is selected from —O—, and —NR 9 —, which is partially unsaturated and optionally substituted with a substituent which is selected from a C 1 -C 3 -alkyl group and a halogen atom,

an aryl group which is optionally substituted with one, two, or three substituents and each substituent is independently selected from a halogen atom, a hydroxy group, a cyano group, a C 1 -C 3 -alkyl group, a C 1 -C 3 -haloalkyl group, and a NR 5 R 6 group;

a mono- or bicyclic heteroaryl group which is optionally substituted with a substituent which is selected from a halogen atom, a C 1 -C 3 -alkyl group a C 1 -C 3 -haloalkyl group, a C 1 -C 3 -alkoxy group, and a NR 5 R 6 group, with the proviso that said monocyclic heteroaryl group is not a pyridin-4-yl group;

and a NR 7 R 8 group;

R 4 is selected from a hydrogen atom, and a C 1 -C 3 -alkyl group;

R 5 /R 6 are independently selected from a hydrogen atom and a C 1 -C 6 -alkyl group;

R 7 /R 8 are independently selected from

a hydrogen atom, with the proviso that R 7 =R 8 =hydrogen is excluded,

a C 1 -C 6 -alkyl group, which is substituted with one, two, three or four substituents and said substituent is independently selected from

a halogen atom;

a cyano group;

a hydroxy group;

a NR 5 R 6 group;

a C 1 -C 3 -alkoxy group;

a C 3 -C 7 -cycloalkyl group which is optionally further substituted with one or two substituents and said substituents are independently selected from a C 1 -C 3 -alkyl group, a oxo (═O) group, a hydroxy group, and a C 1 -C 3 -hydroxyalkyl group;

a 3- to 7-membered heterocycloalkyl group, comprising one, two or three heteroatoms which are independently selected from —O— and —NR 9 —, which is optionally further substituted with a C 1 -C 3 -alkyl group;

a heteroaryl group, which is optionally further substituted with a C 1 -C 3 -alkyl group;

a C 3 -C 7 -cycloalkyl group which is optionally substituted with a hydroxy group, or a C 1 -C 3 -alkyl group and

a 3- to 6-membered heterocycloalkyl group, which is optionally substituted with one or two substituents, said substituent independently selected from C 1 -C 3 -alkyl group and a hydroxy group;

R 9 is a hydrogen atom or a C 1 -C 3 -alkyl group or a bond;

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

4. The compound according to claim 1 ,

where

R 1 is selected from a hydrogen atom, a halogen atom, a C 1 -C 3 -alkyl group, a C 1 -C 3 -haloalkyl group, and a C 1 -C 3 -haloalkoxy group;

R 2 is selected from a hydrogen atom and a halogen atom;

R 3 is selected from,

a C 1 -C 6 -alkyl group which is substituted with a substituent which is selected from a hydroxy group, a C 1 -C 4 -alkoxy group and a 3- to 7-membered heterocycloalkyl group;

a C 2 -C 6 -alkenyl group which is optionally substituted with an C 1 -C 4 -alkoxy group;

a C 4 -C 6 -cycloalkyl group, which is optionally substituted with a hydroxy group;

a C 5 -C 7 -cycloalkenyl group;

a 3- to 6-membered heterocycloalkyl group, comprising one, or two heteroatoms which are independently selected from —O—, and —NR 9 —,

and said heterocycloalkyl group is optionally further substituted with one, or two substituents and each substituent is independently selected from

a halogen atom;

a cyano group;

a hydroxy group;

a C 1 -C 3 -alkyl group which is optionally further substituted with a hydroxy group;

a 5- to 6-membered-heterocycloalkyl group, comprising a heteroatom which is selected from —O—, and —NR 9 —, which is partially unsaturated and optionally substituted with a substituent which is selected from a C 1 -C 3 -alkyl group and a halogen atom;

an aryl group which is optionally substituted with one, or two, substituents and each substituent is independently selected from a halogen atom, a hydroxy group, a cyano group, a C 1 -C 3 -alkyl group, a C 1 -C 3 -haloalkyl group, and a NR 5 R 6 group;

a mono- or bicyclic heteroaryl group which is optionally substituted with a substituent which is selected from a halogen atom, a C 1 -C 3 -alkyl group a C 1 -C 3 -haloalkyl group, a C 1 -C 3 -alkoxy group, and a NR 5 R 6 group, with the proviso that said monocyclic heteroaryl group is not a pyridin-4-yl group;

and a NR 7 R 8 group;

R 4 is selected from a hydrogen atom, and a C 1 -C 3 -alkyl group;

R 5 /R 6 are independently selected from a hydrogen atom and a C 1 -C 6 -alkyl group;

R 7 /R 8 are independently selected from

a hydrogen atom, with the proviso that R 7 =R 8 =hydrogen is excluded,

a C 1 -C 6 -alkyl group, which is substituted with one, two, three or four substituents and said substituent is independently selected from

a halogen atom;

a hydroxy group;

a C 1 -C 3 -alkoxy group;

a C 3 -C 6 -cycloalkyl group which is optionally further substituted with one or two substituents and said substituents are independently selected from a C 1 -C 3 -alkyl group and a C 1 -C 3 -hydroxyalkyl group;

a 4- to 6-membered heterocycloalkyl group, comprising one, two or three heteroatoms which are independently selected from —O— and —NR 9 —, which is optionally further substituted with a C 1 -C 3 -alkyl group;

a heteroaryl group, which is optionally further substituted with a C 1 -C 3 -alkyl group;

a C 3 -C 6 -cycloalkyl group which is optionally substituted with a hydroxy group, or a C 1 -C 3 -alkyl group;

a 3- to 6-membered heterocycloalkyl group, which is optionally substituted with one or two substituents, said substituent independently selected from C 1 -C 3 -alkyl group and a hydroxy group, and

R 9 is a hydrogen atom or a C 1 -C 3 -alkyl group or a bond;

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

5. The compound according to claim 1 , where

R 1 is selected from a hydrogen atom, a halogen atom, a C 1 -C 3 -alkyl group, and a C 1 -C 3 -haloalkyl group;

R 2 is selected from a hydrogen atom and a halogen atom;

R 3 is selected from,

a C 1 -C 6 -alkyl group which is substituted with one or two substituents and each substituent is independently selected from a hydroxy group, a C 1 -C 4 -alkoxy group, and a 3-to 7-membered heterocycloalkyl group;

a C 2 -C 6 -alkenyl group which is optionally substituted with an C 1 -C 3 -alkoxy group;

a C 3 -C 7 -cycloalkyl group, which is optionally substituted with a hydroxy group;

a C 5 -C 6 -cycloalkenyl group, which is optionally substituted with a hydroxy group;

a 3- to 6-membered heterocycloalkyl group, comprising one, two or three heteroatoms which are independently selected from —O— and —NR 9 —,

and said heterocycloalkyl group is optionally substituted with one, two or three substituents and each substituent is independently selected from

a halogen atom;

a oxo (═O) group;

a cyano group;

a hydroxy group;

a C 1 -C 3 -alkyl group which is optionally further substituted with a hydroxy group;

a 5- to 7-membered heterocycloalkyl group which is partially unsaturated and optionally substituted with one or two substituents and each substituent is independently selected from a C 1 -C 3 -alkyl group and a halogen atom;

an aryl group which is optionally substituted with one, two, three or four substituents and each substituent is independently selected from a halogen atom, a hydroxy group, a cyano group, a C 1 -C 3 -alkyl group, a C 1 -C 3 -haloalkyl group, a C 1 -C 3 -alkoxy group, a C 1 -C 3 -haloalkoxy group, and a NR 5 R 6 group;

a mono- or bicyclic heteroaryl group which is optionally substituted with one or two substituents and each substituent is independently selected from a halogen atom, a C 1 -C 3 -alkyl group, a cyano group, a C 1 -C 3 -haloalkyl group, a C 1 -C 3 -alkoxy group, a hydroxy group, and a NR 5 R 6 group, with the proviso that said monocyclic heteroaryl group is not a pyridin-4-yl group;

and a NR 7 R 8 group;

R 4 is selected from a hydrogen atom, and a C 1 -C 3 -alkyl group;

R 5 /R 6 are independently selected from a hydrogen atom and a C 1 -C 6 -alkyl group;

R 7 /R 8 are independently selected from

a hydrogen atom, with the proviso that R 7 =R 8 =hydrogen is excluded,

a C 1 -C 6 -alkyl group, which is substituted with one, two, three or four substituents and said substituent is independently selected from

a halogen atom,

a cyano group,

a hydroxy group,

a C 1 -C 3 -alkoxy group,

a C 3 -C 7 -cycloalkyl group which is optionally substituted with one or two substituents and said substituents are independently selected from a C 1 -C 3 -alkyl group, a hydroxy group, and a C 1 -C 3 -hydroxyalkyl group;

a 3- to 7-membered heterocycloalkyl group which itself is optionally substituted with a C 1 -C 3 -alkyl group;

and a heteroaryl group, which is optionally further substituted with a C 1 -C 3 -alkyl group;

a C 3 -C 6 -cycloalkyl group which is optionally substituted with a hydroxy group, and

a 3- to 6-membered heterocycloalkyl group, which is optionally substituted with one or two substituents said substituent independently selected from C 1 -C 3 -alkyl group and a hydroxy group,

R 9 is a hydrogen atom or a C 1 -C 3 -alkyl group or a bond;

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

6. The compound according to claim 1 ,

where

R 1 is selected from a hydrogen atom, a halogen atom, a C 1 -C 3 -alkyl group, and a C 1 -C 3 -haloalkyl group;

R 2 is selected from a hydrogen atom and a halogen atom;

R 3 is selected from,

a 3- to 6-membered heterocycloalkyl group, comprising one, or two heteroatoms which are independently selected from —O—, and —NR 9 —,

and said heterocycloalkyl group is optionally further substituted with one, or two substituents and each substituent is independently selected from

a halogen atom;

a hydroxy group;

and a C 1 -C 3 -alkyl group which is optionally further substituted with a hydroxy group;

an aryl group which is optionally substituted with one, or two, substituents and each substituent is independently selected from a halogen atom, a hydroxy group, a C 1 -C 3 alkyl group, and a C 1 -C 3 -haloalkyl group;

a mono- or bicyclic heteroaryl group which is optionally substituted with a substituent which is selected from a halogen atom, a C 1 -C 3 -alkyl group a C 1 -C 3 -haloalkyl group and a NR 5 R 6 group, with the proviso that said monocyclic heteroaryl group is not a pyridin-4-yl group;

and a NR 7 R 8 group;

R 4 is selected from a hydrogen atom, and a C 1 -C 3 -alkyl group;

R 5 /R 6 are independently selected from a hydrogen atom and a C 1 -C 3 -alkyl group;

R 7 /R 8 are independently selected from

a hydrogen atom, with the proviso that R 7 =R 8 =hydrogen is excluded,

a C 1 -C 6 -alkyl group, which is substituted with one or two, three or four substituents and said substituent is independently selected from

a halogen atom;

a hydroxy group;

a C 1 -C 3 -alkoxy group;

a C 3 -C 5 -cycloalkyl group which is optionally further substituted with one or two substituents and said substituents are independently selected from a C 1 -C 3 -alkyl group and a C 1 -C 3 -hydroxyalkyl group;

a 5- to 6-membered heterocycloalkyl group, comprising one, or two heteroatoms which are independently selected from —O— and —NR 9 —, which is optionally further substituted with a C 1 -C 3 -alkyl group, a heteroaryl group, which is optionally further substituted with a C 1 -C 3 -alkyl group;

a C 3 -C 6 -cycloalkyl group which is optionally substituted with a hydroxy group, or a C 1 -C 3 -alkyl group;

a 4- to 5-membered heterocycloalkyl group, which is optionally substituted with one or two substituents, said substituent independently selected from C 1 -C 3 -alkyl group and a hydroxy group; and

R 9 is a hydrogen atom or a C 1 -C 3 -alkyl group or a bond;

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

7. The compound according to claim 1 ,

where

R 1 is selected from CF 3 and a fluorine atom;

R 2 is a hydrogen atom;

R 3 is selected from

an aryl group which is optionally substituted with a substituent which is selected from a halogen atom, a C 1 -C 3 alkyl group, and a C 1 -C 3 -haloalkyl group,

a monocyclic heteroaryl group substituted with a substituent which is selected from C 1 -C 3 -haloalkyl group and NR 5 R 6 group;

and a NR 7 R 8 group;

R 4 is selected from a hydrogen atom and a methyl group;

R 5 /R 6 are independently selected from a hydrogen atom and a methyl group;

R 7 /R 8 are independently selected from

a hydrogen atom, with the proviso that R 7 =R 8 =hydrogen is excluded,

a C 1 -C 3 -alkyl group, which is substituted with one, two or four substituents and said substituent is independently selected from

a halogen atom, a hydroxy group, and a methoxy group,

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

8. A compound selected from the group:

5-[4-(4,4-difluoropiperidin-1-yl)-3-fluorophenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-chloro-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4′-fluoro-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(morpholin-4-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(4-fluoro-4-methylpiperidin-1-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(4-fluoropiperidin-1-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(4′-fluoro-2-methylbiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(3′,4′-difluoro-2-methylbiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(4′-fluoro-2,2′-dimethylbiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(3,6-dihydro-2H-pyran-4-yl)-3-methylphenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-methyl-4-(1H-pyrazol-4-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-methyl-4-(6-oxo-1,6-dihydropyridin-3-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-methyl-4-(pyridin-3-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-methyl-4-(pyrimidin-5-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(3′-fluoro-2-methylbiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(rac)-6-methyl-5-(3,4,5-trifluorophenyl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(rac)-5-[3,5-difluoro-4-(morpholin-4-yl)phenyl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(rac)-5-{3,5-difluoro-4-[(2S)-2-methylmorpholin-4-yl]phenyl}-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(rac)-5-(4-bromophenyl)-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one

(rac)-6-methyl-5-[4-(morpholin-4-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3,5-difluoro-4-(morpholin-4-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

2-(morpholin-4-yl)-5-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl) benzonitrile,

3-chloro-2-(morpholin-4-yl)-5-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)benzonitrile,

5-{4-[2,6-dimethylmorpholin-4-yl]-3-fluorophenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-(3-Fluoro-4-morpholinophenyl)-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-(3,5-Difluoro-4-morpholinophenyl)-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(3,3-difluoropyrrolidin-1-yl)-3-fluorophenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2-methylbiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-methyl-4-(2-methylpyrimidin-5-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-methyl-4-(1-methyl-1H-pyrazol-5-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2,4′-difluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4′-chloro-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(6-methylpyridin-3-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(pyridin-3-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4′-amino-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3′-hydroxy-4′-methyl-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{3-(trifluoromethyl)-4-[6-(trifluoromethyl)pyridin-3-yl]phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4′-fluoro-3′-hydroxy-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[5′-amino-2′,4′-difluoro-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4′-amino-3′-fluoro-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(6-aminopyridin-3-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3′-amino-4′-chloro-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3′-amino-4′-methyl-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3′-amino-2′-fluoro-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4′-amino-2′-fluoro-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(1-methyl-1H-pyrazol-4-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(3-methyl-1H-pyrazol-4-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(1H-indazol-6-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(5-fluoro-6-methylpyridin-3-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(1,2-thiazol-4-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

1-methyl-5-[4-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)-2-(trifluoromethyl)phenyl]-1H-pyrrole-2-carbonitrile,

5-[2,4′-bis (trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(1,3-dimethyl-1H-pyrazol-4-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(2-methoxy-6-methylpyridin-3-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(2-methyl-1,3-thiazol-5-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4′-(methylamino)-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3′-amino-4′-fluoro-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-fluoro-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3′,4′,5′-trifluoro-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[2′,5′-difluoro-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3′-amino-4′-fluoro-2-(trifluoromethoxy) biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3′,4′-difluoro-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(1H-indol-6-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(2-methylprop-1-en-1-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[2′,3′-difluoro-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(morpholin-4-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(butylamino)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(ethylamino)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(1-methyl-1H-pyrazol-4-yl)-3-(trifluoromethoxy)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(propylamino)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(6-methylpyridin-3-yl)-3-(trifluoromethoxy)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4′-chloro-2-(trifluoromethoxy) biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(azetidin-1-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(1-methyl-1H-benzimidazol-6-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(pentylamino)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(1-methyl-1H-indazol-6-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4′-fluoro-2-(trifluoromethoxy) biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(6-fluoropyridin-3-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(3-methylpyridin-4-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(2-methylpyridin-4-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(4′-amino-2-fluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2-fluoro-2′-methylbiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2′-chloro-2,4′-difluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(cyclopent-1-en-1-yl)-3-fluorophenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2′-ethyl-2-fluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2,4′-difluoro-3′-methylbiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2-fluoro-3′-methylbiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2-fluoro-4′-methylbiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2-fluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(2-aminopyridin-4-yl)-3-fluorophenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(3′-amino-2-fluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4′-(difluoromethyl)-2-fluorobiphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(pyridin-4-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(2-methylpyrimidin-5-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(2-methoxypyridin-4-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(2-methylpyridin-3-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(6-methylpyridin-3-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2,2′, 4′,5′-tetrafluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2,2′,3′,4′-tetrafluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2,2′, 5′-trifluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

2′-fluoro-4′-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl) biphenyl-4-carbonitrile,

5-(2′-amino-2-fluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(3′-amino-2-fluoro-4′-methylbiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2-fluoro-3′-hydroxybiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2-fluoro-4′-hydroxybiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2-fluoro-2′-hydroxybiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2,3′,4′-trifluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(pyridin-3-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2,2′,3′-trifluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2,3′,5′-trifluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2,2′,4′-trifluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2-fluoro-2′,4′-dimethylbiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2,3′-difluoro-4′-methylbiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2,2′-difluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2,2′,6′-trifluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2-fluoro-2′-methoxybiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2,3′-difluorobiphenyl-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(4-methylpyridin-3-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(rac)-5-(3-Fluoro-4-morpholinophenyl)-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-6-methyl-5-[4-(morpholin-4-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-(-[(3-chloro-4-(morpholin-4-yl)-5-(trifluoromethyl)phenyl)-)]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

6S)-5-(-[(4-chloro-3-(trifluoromethyl)phenyl)-)]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-(-[(4-fluoro-3-(trifluoromethyl)phenyl)-)]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-chloro-3-(trifluoromethoxy)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(4-chloro-3-methylphenyl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(rac)-6-methyl-5-(4-morpholino-3-(trifluoromethyl)phenyl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(3,5-dimethyl-1H-pyrazol-4-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(3,5-dimethyl-1,2-oxazol-4-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{3-(trifluoromethyl)-4-[3-(trifluoromethyl)-1H-pyrazol-4-yl]phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(1-ethyl-1H-pyrazol-4-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[cyclopentyl(methyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[butyl(methyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[4′-fluoro-2-(trifluoromethyl)biphenyl-4-yl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(cyclopentylamino)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(cyclopentylamino)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3′-fluoro-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-methyl-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[3-methoxyprop-1-en-1-yl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(rac)-5-[4′-hydroxy-2-(trifluoromethyl)-2′,3′,4′,5′-tetrahydro [1,l′-biphenyl]-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(5,6-dihydro-2H-pyran-3-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(imidazo [1,2-a]pyridin-6-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[3,3-dimethylbut-1-en-1-yl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{3-(trifluoromethyl)-4-[5-(trifluoromethyl) thiophen-3-yl]phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[1-(difluoromethyl)-1H-pyrazol-4-yl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(prop-1-en-2-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(1-benzothiophen-2-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(2,5-dihydrofuran-3-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(cyclopent-1-en-1-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(1-ethyl-1H-imidazol-4-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

3-methyl-5-[4-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)-2-(trifluoromethyl)phenyl]thiophene-2-carbonitrile,

5-{4-[1-(propan-2-yl)-1H-pyrazol-4-yl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(rac)-5-[4-(bicyclo[2.2.1]hept-2-en-2-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[2′-fluoro-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{3-(Trifluoromethyl)-4-[5-(trifluoromethyl) thiophen-2-yl]phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(5-methylpyridin-2-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(5-fluoropyridin-2-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(5-chloropyridin-2-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(pyridin-2-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[2′-(Difluoromethyl)-2-fluoro [1,1′-biphenyl]-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-(2,4′-Difluoro-2′-methyl [1,l′-biphenyl]-4-yl)-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

2′-fluoro-2-methyl-4′-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)[1,1′-biphenyl]-4-carbonitrile,

5-[4-(2-Methylprop-1-en-1-yl)-3-(trifluoromethoxy)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[4-(2-aminopyridin-4-yl)-3-(trifluoromethyl)phenyl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-6-methyl-5-[4-(pyridin-4-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-6-methyl-5-[4-(6-methylpyridin-3-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[2′-fluoro-4′-methyl-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-6-methyl-5-[2′,4′,5′-trifluoro-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-6-methyl-5-[2′,3′,4′-trifluoro-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[2′,5′-difluoro-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

4′-[(6S)-6-methyl-2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl]-2′-(trifluoromethyl)[1,1′-biphenyl]-2-carbonitrile,

(6S)-5-[4-(1H-indol-5-yl)-3-(trifluoromethyl)phenyl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[4′-hydroxy-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[3′-hydroxy-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[3′-amino-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[2′,4′-difluoro-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[3′-fluoro-4′-methyl-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[2′-fluoro-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[2′-methoxy-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[3′-fluoro-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-6-methyl-5-[4-(4-methylpyridin-3-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-6-methyl-5-[4-(3-methylpyridin-4-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-6-methyl-5-[4-(2-methylpyridin-4-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[4-(1H-indol-6-yl)-3-(trifluoromethyl)phenyl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[4-(6-methoxypyridin-3-yl)-3-(trifluoromethyl)phenyl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[4′-methoxy-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-6-methyl-5-[4′-methyl-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-{4-[1-(difluoromethyl)-1H-pyrazol-4-yl]-3-(trifluoromethyl)-phenyl}-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[1-(difluoromethyl)-1H-pyrazol-4-yl]-3-(trifluoromethyl)-phenyl}-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4′-fluoro-2-(trifluoromethyl)[1,1′-biphenyl]-4-yl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[1-(difluoromethyl)-1H-pyrazol-4-yl]-3-fluoro-5-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{3-(difluoromethyl)-4-[1-(difluoromethyl)-1H-pyrazol-4-yl]phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-6-methyl-5-{4-[(morpholin-4-yl)methyl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(morpholin-4-yl)methyl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[2-(difluoromethyl)-4′-fluoro [1,1′-biphenyl]-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4′-chloro-2-(difluoromethyl)[1,1′-biphenyl]-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-(difluoromethyl)-4-(6-methylpyridin-3-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(cyclopent-1-en-1-yl)-3-(difluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(3-Hydroxy-3-methylazetidin-1-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(rac)-5-[4-{[3,3,3-trifluoro-2-hydroxypropyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(Oxan-4-yl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[(cis/trans)-3-hydroxycyclobutyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(rac)-2,4-Dimethylazetidin-1-yl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(cis or trans)-2,4-Dimethylazetidin-1-yl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[3,3,3-Trifluoro-2(S)-hydroxypropyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(2-Hydroxy-2-methylpropyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[(trans)-4-Hydroxycyclohexyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(Cyclopropylmethyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[(3-Methyloxetan-3-yl)methyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

{4-[(3-Methoxypropyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-({[(rac)-Oxolan-2-yl]methyl}amino)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[2(R)-2-Hydroxypropyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[(3R)-3-Hydroxybutyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[(2S)-2-Hydroxypropyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[(1-Hydroxycyclobutyl)methyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(3-Methylbutyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(2-Methylpropyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(2-Methoxyethyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[Ethyl(methyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(tert-butylamino)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-({[(2R)-oxolan-2-yl]methyl}amino)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[(pyrazin-2-yl)methyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(4-hydroxypiperidin-1-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[(2S)-1-hydroxybutan-2-yl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(3-hydroxypiperidin-1-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one (racemic mixture),

(rac)-1-[4-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)-2-(trifluoromethyl)phenyl] piperidine-3-carboxamide,

5-{4-[(3-hydroxy-2,2-dimethylpropyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(4,4-difluoropiperidin-1-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[(1R,2R,4R)-bicyclo[2.2.1]heptan-2-yl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(3S)-3-hydroxypyrrolidin-1-yl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(rac)-5-{4-[(2-hydroxy-3-methoxypropyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[(1-methyl-1H-pyrazol-5-yl)methyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[(1H-pyrazol-3-yl)methyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[2-(1H-pyrazol-1-yl) ethyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

1-[4-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)-2-(trifluoromethyl)phenyl] piperidine-4-carbonitrile,

(rac)-5-{4-[(1-cyclopropylethyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(rac)-5-{4-[(2-ethoxypropyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one

(rac)-5-{4-[(2-methoxypropyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one

5-[4-(3-ethoxyazetidin-1-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[(pyrimidin-2-yl)methyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[(oxolan-3-yl)methyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one (racemic mixture),

5-[4-{[(2S)-4-hydroxybutan-2-yl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(rac)-5-[4-{[(6-oxopiperidin-3-yl)methyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(rac)-5-[4-{[(2,2-dimethylcyclopropyl)methyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-({[1-(hydroxymethyl)cyclobutyl]methyl}amino)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(2S)-2-(hydroxymethyl) azetidin-1-yl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

3-methyl-1-[4-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)-2-(trifluoromethyl)phenyl] azetidine-3-carbonitrile,

5-[4-(3-azabicyclo[3.1.0]hexan-3-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(4-ethyl-4-hydroxypiperidin-1-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

4-[4-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)-2-(trifluoromethyl) anilino] butanenitrile,

6-[4-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)-2-(trifluoro-methyl)phenyl]-2lambda 6 -thia-6-azaspiro[3.3]heptane-2,2-dione,

N 2 -[4-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)-2-(trifluoromethyl)phenyl] glycinamide,

5-{4-[(3R)-3-hydroxypyrrolidin-1-yl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(2-methoxy-2-methylpropyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one

5-[4-({[(2S)-oxolan-2-yl]methyl}amino)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(2-ethoxyethyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-{[(1S,2R)-2-hydroxycyclopentyl]amino}-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(oxetan-3-yl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-on,

5-{3-(difluoromethyl)-4-[1-(propan-2-yl)-1H-pyrazol-4-yl]phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[3-fluoro-4-(morpholin-4-yl)-5-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-6-methyl-5-{3-(trifluoromethyl)-4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-6-methyl-5-{3-(trifluoromethyl)-4-[4-(trifluoromethyl)-1H-imidazol-1-yl]phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(3-Methoxypropyl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(2-methylpropyl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(3,3-dimethylbutyl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(Propan-2-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(rac)-5-{4-[oxan-3-yl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(trans)-5-{4-[4-hydroxycyclohexyl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one (trans isomer),

(cis)-5-{4-[4-hydroxycyclohexyl]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-{4-[(2-Aminoethyl)amino]-3-(trifluoromethyl)phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one-salt with hydrochloric acid,

5-{4-[1-amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-(trifluoromethyl)-phenyl}-3,6-dihydro-2H-1,3,4-oxadiazin-2-one-salt with hydrochloric acid,

5-[4-(methylamino)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-6-methyl-5-[4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

5-[4-(2-hydroxypropan-2-yl)-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one,

(6S)-5-[4-(3,3-difluoroazetidin-1-yl)-3-(trifluoromethyl)phenyl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one and

(6S)-5-[4-(3-hydroxy-3-methylazetidin-1-yl)-3-(trifluoromethyl)-phenyl]-6-methyl-3,6-dihydro-2H-1,3,4-oxadiazin-2-one

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

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

10. A pharmaceutical combination comprising:

one or more compounds of general formula (I) according to claim 1 , and

one or more further anti-cancer agents.

11. A method for the treatment of a disease sensitive to phosphodiesterase 3A (PDE3A) or phosphodiesterase 3B (PDE3B) modulation in a subject, comprising administering to the subject a compound having the structure of formula (I):

where

R 1 is selected from a hydrogen atom, a halogen atom, a cyano group, a C 1 -C 3 -alkyl group, a C 1 -C 3 -haloalkyl group, and a C 1 -C 3 -haloalkoxy group;

R 2 is selected from a hydrogen atom and a halogen atom;

R 3 is selected from,

a C 1 -C 6 -alkyl group which is optionally substituted with one or two substituents and each substituent is independently selected from a hydroxy group, a C 1 -C 4 -alkoxy group and a 3-to 7-membered heterocycloalkyl group;

a C 2 -C 6 -alkenyl group which is optionally substituted with an C 1 -C 4 -alkoxy group;

a C 3 -C 9 -cycloalkyl group, which is optionally substituted with a hydroxy group;

a C 5 -C 9 -cycloalkenyl group, which is optionally substituted with a hydroxy group;

a 3- to 9-membered heterocycloalkyl group, comprising one, two or three heteroatoms which are independently selected from —O—, —S—, —S(O)—, S(O) 2 , and —NR 9 —,

and said heterocycloalkyl group optionally further comprising a bridging group selected from —O—, —NR 9 —, —CH 2 —, —CH 2 —CH 2 —, —O—CH 2 —, —CH 2 —O—, —NR 9 —CH 2 —, and —CH 2 —NR 9 —;

and said heterocycloalkyl group is optionally substituted with one, two or three substituents and each substituent is independently selected from

a halogen atom;

a oxo (═O) group;

a cyano group;

a hydroxy group;

a C 1 -C 3 -alkyl group which is optionally further substituted with a hydroxy group;

a C 1 -C 3 -haloalkyl group;

a C 1 -C 3 -alkoxy group;

a C 1 -C 3 -haloalkoxy group;

a C(O)NR 5 R 6 group

and a NR 5 R 6 group;

a 5- to 9-membered heterocycloalkyl group which is partially unsaturated and optionally substituted with one, two or three substituents and each substituent is independently selected from an oxo group (═O), a C 1 -C 3 -alkyl group, a —C(O)R 5 R 6 group and a halogen atom;

an aryl group which is optionally substituted with one, two, three or four substituents and each substituent is independently selected from a halogen atom, a hydroxy group, a cyano group, a C 1 -C 3 -alkyl group, a C 1 -C 3 -haloalkyl group, a C 1 -C 3 -alkoxy group, a C 1 -C 3 -haloalkoxy group, and a NR 5 R 6 group;

a mono- or bicyclic heteroaryl group which is optionally substituted with one, two or three substituents and each substituent is independently selected from a halogen atom, a C 1 -C 3 -alkyl group, a cyano group, a C 1 -C 3 -haloalkyl group, a C 1 -C 3 -hydroxalkyl group, a C 1 -C 3 -alkoxy group, a hydroxy group, and a NR 5 R 6 group, with the proviso that said monocyclic heteroaryl group is not 4-pyridyl;

and a NR 7 R 8 group;

R 4 is selected from a hydrogen atom, and a C 1 -C 3 -alkyl group;

R 5 /R 6 are independently selected from a hydrogen atom, a C 1 -C 6 -alkyl group, a —C 1 -C 5 -alkylene-O—C 1 -C 5 -alkyl group, a —C 1 -C 5 -alkylene-S—C 1 -C 5 -alkyl group, C 3 -C 6 -cycloalkyl group, and a C 3 -C 5 -heterocycloalkyl group;

R 7 /R 8 are independently selected from a hydrogen atom, with the proviso that R 7 =R 8 =hydrogen is excluded,

a C 1 -C 6 -alkyl group, which is optionally substituted with one, two, three or four substituents and said substituent is independently selected from

a halogen atom,

a cyano group,

a hydroxy group,

a C(O)NR 5 R 6 group,

a NR 5 R 6 group,

a C 1 -C 3 -alkoxy group,

a C 3 -C 7 -cycloalkyl group which is optionally substituted with one or two substituents and said substituents are independently selected from a C 1 -C 3 -alkyl group, a oxo (═O) group, a hydroxy group, and a C 1 -C 3 -hydroxyalkyl group;

a 3- to 7-membered heterocycloalkyl group which itself is optionally substituted with, a C 1 -C 3 -alkyl group or an oxo (═O) group;

a heteroaryl group, which itself is optionally substituted with a C 1 -C 3 -alkyl group;

a —C 1 -C 5 -alkylene-O—C 1 -C 5 -alkyl group;

a —C 1 -C 5 -alkylene-S—C 1 -C 5 -alkyl group;

a —C 1 -C 5 -alkylene-NR 5 —C 1 -C 5 -alkyl group;

a C 3 -C 6 -cycloalkyl group which is optionally substituted with a hydroxy group; and

a 3- to 6-membered heterocycloalkyl group, which is optionally substituted with one or two substituents, said substituent independently selected from C 1 -C 3 -alkyl group and a hydroxy group;

R 9 is a hydrogen atom or a C 1 -C 3 -alkyl group or a bond;

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

12. A method for the preparation of a medicament for the treatment of a disease sensitive to phosphodiesterase 3A (PDE3A) or phosphodiesterase 3B (PDE3B) modulation, comprising mixing the compound of general formula (I)

where

R 1 is selected from a hydrogen atom, a halogen atom, a cyano group, a C 1 -C 3 -alkyl group, a C 1 -C 3 -haloalkyl group, and a C 1 -C 3 -haloalkoxy group;

R 2 is selected from a hydrogen atom and a halogen atom;

R 3 is selected from,

a C 1 -C 6 -alkyl group which is optionally substituted with one or two substituents and each substituent is independently selected from a hydroxy group, a C 1 -C 4 -alkoxy group and a 3-to 7-membered heterocycloalkyl group;

a C 2 -C 6 -alkenyl group which is optionally substituted with an C 1 -C 4 -alkoxy group;

a C 3 -C 9 -cycloalkyl group, which is optionally substituted with a hydroxy group;

a C 5 -C 9 -cycloalkenyl group, which is optionally substituted with a hydroxy group;

a 3- to 9-membered heterocycloalkyl group, comprising one, two or three heteroatoms which are independently selected from —O—, —S—, —S(O)—, S(O) 2 , and —NR 9 —,

and said heterocycloalkyl group optionally further comprising a bridging group selected from —O—, —NR 9 —, —CH 2 —, —CH 2 —CH 2 —, —O—CH 2 —, —CH 2 —O—, —NR 9 —CH 2 —, and —CH 2 —NR 9 —;

and said heterocycloalkyl group is optionally substituted with one, two or three substituents and each substituent is independently selected from

a halogen atom;

a oxo (═O) group;

a cyano group;

a hydroxy group;

a C 1 -C 3 -alkyl group which is optionally further substituted with a hydroxy group;

a C 1 -C 3 -haloalkyl group;

a C 1 -C 3 -alkoxy group;

a C 1 -C 3 -haloalkoxy group;

a C(O)NR 5 R 6 group

and a NR 5 R 6 group;

a 5- to 9-membered heterocycloalkyl group which is partially unsaturated and optionally substituted with one, two or three substituents and each substituent is independently selected from an oxo group (═O), a C 1 -C 3 -alkyl group, a —C(O)R 5 R 6 group and a halogen atom;

an aryl group which is optionally substituted with one, two, three or four substituents and each substituent is independently selected from a halogen atom, a hydroxy group, a cyano group, a C 1 -C 3 -alkyl group, a C 1 -C 3 -haloalkyl group, a C 1 -C 3 -alkoxy group, a C 1 -C 3 -haloalkoxy group, and a NR 5 R 6 group;

a mono- or bicyclic heteroaryl group which is optionally substituted with one, two or three substituents and each substituent is independently selected from a halogen atom, a C 1 -C 3 -alkyl group, a cyano group, a C 1 -C 3 -haloalkyl group, a C 1 -C 3 -hydroxalkyl group, a C 1 -C 3 -alkoxy group, a hydroxy group, and a NR 5 R 6 group, with the proviso that said monocyclic heteroaryl group is not 4-pyridyl;

and a NR 7 R 8 group;

R 4 is selected from a hydrogen atom, and a C 1 -C 3 -alkyl group;

R 5 /R 6 are independently selected from a hydrogen atom, a C 1 -C 6 -alkyl group, a —C 1 -C 5 -alkylene-O—C 1 -C 5 -alkyl group, a —C 1 -C 5 -alkylene-S—C 1 -C 5 -alkyl group, C 3 -C 6 -cycloalkyl group, and a C 3 -C 5 -heterocycloalkyl group;

R 7 /R 8 are independently selected from a hydrogen atom, with the proviso that R 7 =R 8 =hydrogen is excluded,

a C 1 -C 6 -alkyl group, which is optionally substituted with one, two, three or four substituents and said substituent is independently selected from

a halogen atom,

a cyano group,

a hydroxy group,

a C(O)NR 5 R 6 group,

a NR 5 R 6 group,

a C 1 -C 3 -alkoxy group,

a C 3 -C 7 -cycloalkyl group which is optionally substituted with one or two substituents and said substituents are independently selected from a C 1 -C 3 -alkyl group, a oxo (═O) group, a hydroxy group, and a C 1 -C 3 -hydroxyalkyl group;

a 3- to 7-membered heterocycloalkyl group which itself is optionally substituted with, a C 1 -C 3 -alkyl group or an oxo (═O) group;

a heteroaryl group, which itself is optionally substituted with a C 1 -C 3 -alkyl group;

a —C 1 -C 5 -alkylene-O—C 1 -C 5 -alkyl group;

a —C 1 -C 5 -alkylene-S—C 1 -C 5 -alkyl group;

a —C 1 -C 5 -alkylene-NR 5 —C 1 -C 5 -alkyl group;

a C 3 -C 6 -cycloalkyl group which is optionally substituted with a hydroxy group; and

a 3- to 6-membered heterocycloalkyl group, which is optionally substituted with one or two substituents, said substituent independently selected from C 1 -C 3 -alkyl group and a hydroxy group;

R 9 is a hydrogen atom or a C 1 -C 3 -alkyl group or a bond;

or a stereoisomer, a tautomer, an N-oxide, or a salt thereof, or a mixture of same;

with one or more pharmaceutically acceptable excipients.

13. The method according to claim 11 , wherein the disease is a hyperproliferative disease.

14. The method according to claim 13 , wherein the hyperproliferative disease is a cancer disease.

15. The method according to claim 14 , wherein the cancer disease is selected from brain cancer, breast cancer, cervical cancer, AML, lung cancer, skin cancer, esophageal carcinoma, ovarian cancer, pancreas cancer and prostate cancer.

Assignments (3)

Continuity (3)

References Cited (75)