US 2020/0369633 A1 · DIHYDROOXADIAZINONES

Abstract

The present invention provides dihydrooxydiazinone compounds of general formula (I): in which R1, R2, R3, and R4, are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative diseases, as a sole agent or in combination with other active ingredients.

A compound of formula (I)

where
R1 is selected from a hydrogen atom, a halogen atom, a cyano group, a C1-C3-alkyl group, a C1-C3-haloalkyl group, and a C1-C3-haloalkoxy group;
R2 is selected from a hydrogen atom and a halogen atom;
R3 is selected from,
a C1-C6-alkyl group which is optionally substituted with one or two substituents and each substituent is independently selected from a hydroxy group, a C1-C4-alkoxy group and a 3- to 7-membered heterocycloalkyl group;
a C2-C6-alkenyl group which is optionally substituted with an C1-C4-alkoxy group;
a C3-C9-cycloalkyl group, which is optionally substituted with a hydroxy group;
a C5-C9-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 —NR9—,
and said heterocycloalkyl group optionally further comprising a bridging group selected from —O—, —NR9—, —CH2—, —CH2—CH2—, —O—CH2—, —CH2—O—, —NR9—CH2—, and —CH2—NR9—;
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 C1-C3-alkyl group which is optionally further substituted with a hydroxy group;
a C1-C3-haloalkyl group;
a C1-C3-alkoxy group;
a C1-C3-haloalkoxy group;
a C(O)NR5R6 group
and a NR5R6 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 C1-C3-alkyl group, a —C(O)R5R6 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 C1-C3-alkyl group, a C1-C3-haloalkyl group, a C1-C3-alkoxy group, a C1-C3-haloalkoxy group, and a NR5R6 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 C1-C3-alkyl group, a cyano group, a C1-C3-haloalkyl group, a C1-C3-hydroxyalkyl group, a C1-C3-alkoxy group, a hydroxy group, and a NR5R6 group, with the proviso that said monocyclic heteroaryl group is not 4-pyridyl;
and a NR7R8 group;
R4 is selected from a hydrogen atom, and a C1-C3-alkyl group;
R5/R6 are independently selected from a hydrogen atom, a C1-C6-alkyl group, a —C1-C5-alkylene-O—C1-C5-alkyl group, a —C1-C5-alkylene-S—C1-C5-alkyl group, C3-C6-cycloalkyl group, and a C3-C5-heterocycloalkyl group;
R7/R8 are independently selected from a hydrogen atom, with the proviso that R7═R8=hydrogen is excluded,
a C1-C6-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)NR5R6 group,
a NR5R6 group,
a C1-C3-alkoxy group,
a C3-C7-cycloalkyl group which is optionally substituted with one or two substitutents and said substituents are independently selected from a C1-C3-alkyl group, a oxo (═O) group, a hydroxy group, and a C1-C3-hydroxyalkyl group;
a 3- to 7-membered heterocycloalkyl group which itself is optionally substituted with, a C1-C3-alkyl group or an oxo (═O) group;
a heteroaryl group, which itself is optionally substituted with a C1-C3-alkyl group;
a —C1-C5-alkylene-O—C1-C5-alkyl group;
a —C1-C5-alkylene-S—C1-C5-alkyl group;
a —C1-C5-alkylene-NR5—C1-C5-alkyl group;
a C3-C6-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 C1-C3-alkyl group and a hydroxy group;
R9 is a hydrogen atom or a C1-C3-alkyl group or a bond;
or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

44 more elements

Dihydrooxadiazinones

Life of this patent

Dihydrooxadiazinones

Life of this patent

Abstract

Claims22