US 2019/0241562 A1 · 7-SUBSTITUTED 1-PYRIDYL-NAPHTHYRIDINE-3-CARBOXYLIC ACID AMIDES AND USE THEREOF

1:

A compound of the formula (I)
in which
R1 represents NR3R4,
in which
R3 represents hydrogen, methyl, (C2-C4)-alkyl or (C3-C6)-cycloalkyl,
where (C2-C4)-alkyl may be substituted by hydroxy or up to trisubstituted by fluorine and
R4 represents (C1-C6)-alkyl, (C3-C6)-cycloalkyl, 3- to 6-membered saturated heterocyclyl or (C1-C4)-alkylsulfonyl,
where (C1-C6)-alkyl, (C3-C6)-cycloalkyl and 3- to 6-membered saturated heterocyclyl may be up to trisubstituted by identical or different substituents from the group consisting of methyl, difluoromethyl, trifluoromethyl, hydroxy, hydroxycarbonyl, oxo, methoxy, difluoromethoxy, trifluoromethoxy and cyano and furthermore up to tetrasubstituted by fluorine,
or
R3 and R4 together with the nitrogen atom to which they are attached form a saturated or partially unsaturated 3- to 6-membered monocyclic or 6- to 10-membered bicyclic heterocycle which may contain one or two further identical or different heteroatoms from the group consisting of N, O, S, SO and SO2 as ring members,
where the 3- to 6-membered monocyclic and the 6- to 10-membered bicyclic heterocycle may each be substituted by 1 to 5 substituents independently selected from the group of (C1-C4)-alkyl, difluoromethyl, trifluoromethyl, hydroxy, hydroxycarbonyl, oxo, (C1-C3)alkoxy, difluoromethoxy, trifluoromethoxy, cyano, (C1-C3)-alkoxycarbonyl, aminocarbonyl, mono-(C1-C3)-alkylaminocarbonyloxy, —NHC(═O)R14A and —CH2NHC(═O)R14B, and additionally up to tetrasubstituted by fluorine, in which
R14A and R14B independently represent (C1-C3)-alkyl or cyclopropyl, and
where (C1-C4)-alkyl may be mono- or disubstituted by identical or different substituents from the group consisting of hydroxy and (C1-C3)-alkoxy, and up to tetrasubstituted by fluorine,
R2 represents a group of the formula
in which
* marks the point of attachment to the nitrogen atom of the amide moiety,
R5A represents hydrogen or (C1-C4)-alkyl,
R5B represents hydrogen, (C1-C4)-alkyl, cyclopropyl, monofluoromethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, methoxymethyl or trifluoromethoxymethyl,
R6 represents (C1-C4)-alkyl which is up to pentasubstituted by fluorine, or (C3-C5)cycloalkyl which is up to tetrasubstituted by fluorine,
Y1 is —(CH2)k—, —CF2—, —O—CH2—, —CH2—O— or —CH2—O—CH2—,
in which
k represents 0, 1, 2 or 3,
R7 represents hydrogen, (C1-C2)-alkyl which is up to pentasubstituted by fluorine, or trifluoromethoxymethyl,
L1 represents a bond or a group of the formula —C(R8AR8B)—(C(R9AR9B))m—,
in which
m represents 0 or 1,
R8A represents hydrogen or methyl,
R8B represents hydrogen, methyl, trifluoromethyl, pentafluoroethyl or trifluoromethoxymethyl,
R9A and R9B independently represent hydrogen or methyl,
Ar2 represents phenyl,
where phenyl may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, (C1-C3)-alkyl, difluoromethoxymethyl, trifluoromethoxymethyl and trifluoromethyl,
or
represents a 5- to 10-membered bicyclic or tricyclic carbocycle,
where the 5- to 10-membered bicyclic or tricyclic carbocycle may be up to trisubstituted, identically or differently, by (C1-C3)-alkyl and trifluoromethyl, and additionally up to tetrasubstituted by fluorine,
Ar1 represents a pyridine ring which is attached via a ring carbon atom,
where the pyridine ring may be mono- or disubstituted by fluorine, chlorine, cyano, methyl or trifluoromethyl,
and the N-oxides, salts, solvates, salts of the N-oxides and solvates of the N-oxides and salts thereof.

34 more elements

2:

The compound accordingly to claim 1,
in which
R1 represents NR3R4,
in which
R3 represents hydrogen, methyl or (C2-C4)-alkyl, and
R4 represents (C1-C6)-alkyl which is up to tetrasubstituted by fluorine,
where (C1-C6)-alkyl may be substituted by oxo,
or
R3 and R4 together with the nitrogen atom to which they are attached form a saturated 4- to 6-membered monocyclic or 6- to 9-membered bicyclic heterocycle which may contain one or two further identical or different heteroatoms from the group consisting of N and O as ring members,
where the 4- to 6-membered monocyclic and 6- to 9-membered bicyclic heterocycle may each be substituted by 1 to 5 substituents independently selected from the group of (C1-C4)-alkyl, difluoromethyl, trifluoromethyl, hydroxy, oxo, (C1-C3)-alkoxy, difluoromethoxy, trifluoromethoxy, and furthermore up to tetrasubstituted by fluorine,
where (C1-C4)-alkyl may be mono- or disubstituted by identical or different substituents from the group consisting of hydroxy and (C1-C3)-alkoxy, and up to tetrasubstituted by fluorine,
R2 represents a group of the formula
in which
* marks the point of attachment to the nitrogen atom of the amide moiety,
R5A represents hydrogen or (C1-C4)-alkyl,
R5B represents methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl or trifluoromethoxymethyl, and
R6 represents (C1-C4)-alkyl which is up to pentasubstituted by fluorine, or (C3-C5)cycloalkyl which is up to tetrasubstituted by fluorine,
Y1 represents —(CH2)k—,
in which
k represents 1 or 2,
R7 represents (C1-C2)-alkyl which is up to pentasubstituted by fluorine,
R10 represents hydrogen, fluorine or trifluoromethyl,
L1 represents a bond or a group of the formula —CR8AR8B—,
in which
R8A represents hydrogen,
R8B represents methyl, trifluoromethyl, pentafluoroethyl or trifluoromethoxymethyl,
Ar2 represents phenyl,
where phenyl may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, (C1-C3)-alkyl and trifluoromethyl,
Ar1 represents a pyridine ring which is attached via a ring carbon atom,
where the pyridine ring may be mono- or disubstituted by fluorine, chlorine, cyano, methyl or trifluoromethyl,
and the N-oxides, salts, solvates, salts of the N-oxides and solvates of the N-oxides and salts thereof.

28 more elements

3:

The compound accordingly to claim 1,
in which
R1 represents NR3R4,
in which
R3 represents hydrogen or methyl, and
R4 represents methyl or 2-fluoroethyl,
or
represents a heterocycle, attached via a nitrogen atom, of the formula
in which
** marks the point of attachment to the remainder of the molecule
Y2 represents a group of the formula
in which
#1 marks the point of attachment to the nitrogen atom of the pyrrolidinone ring, and
#2 marks the point of attachment to the carbon atom of the pyrrolidinone ring, and
Y3 represents —N(R12)— or a group of the formula
in which
#1 and #2 each mark the point of attachment to the carbon atom of the pyrrolidinone hydroxymethyl, methoxy, difluoromethoxy or trifluoromethoxy,
R11 represents fluorine, (C1-C4)-alkyl, difluoromethyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxy, difluroromethoxy or trifluoromethoxy,
p represents the number 0, 1, 2, 3 or 4,
where, in the case that the substituents R11 occur more than once, their meanings may in each case be identical or different,
R12 represents hydrogen or 2-hydroxyethyl,
R2 represents a group of the formula
in which
* marks the point of attachment to the nitrogen atom of the amide moiety,
R5A is hydrogen or methyl,
R5B represents methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl or trifluoromethoxymethyl, and
R6 represents methyl, ethyl, trifluoromethyl, 2,2,2-trifluoroethyl, tert-butyl, isobutyl or cyclopropyl,
Y1 represents —(CH2)k—,
in which
k represents 1 or 2,
R7 represents trifluoromethyl,
R10 represents hydrogen, fluorine or trifluoromethyl,
L1 represents a bond or a group of the formula —CR8AR8B—,
in which
R8A represents hydrogen,
R8B represents trifluoromethyl,
Ar2 represents phenyl,
where phenyl may be mono- or disubstituted by identical or different substituents from the group consisting of fluorine and chlorine,
Ar1 represents a group of the formula
in which
*** marks the point of attachment to the nitrogen atom,
R13A represents fluorine or chlorine,
R13B represents fluorine or hydrogen,
and the salts, solvates and solvates of the salts thereof.

41 more elements

7-substituted 1-pyridyl-naphthyridine-3-carboxylic acid amides and use thereof

Life of this patent

7-substituted 1-pyridyl-naphthyridine-3-carboxylic acid amides and use thereof

Life of this patent

Abstract

Claims15