US 2012/0238607 A1 · SUBSTITUTED 2-ACETAMIDO-5-ARYL-1,2,4-TRIAZOLONES AND USE THEREOF

Abstract

The present application relates to new, substituted 2-acetamido-5-aryl-1,2,4-triazolones, to processes for preparing them, to their use alone or in combinations for the treatment and/or prevention of diseases and also to their use for the production of medicaments for the treatment and/or prevention of diseases, more particularly for the treatment and/or prevention of cardiovascular disorders.

A compound of the formula (I)

in which
A is —C(R6AR6B)—* or —C(R6AR6B)—C(R7AR7B) —*,
where
* is the attachment site to R3,
R6A is hydrogen, (C1-C4) alkyl or trifluoromethyl,
R6B is hydrogen or (C1-C4) alkyl,
R7A is hydrogen, (C1-C4) alkyl or trifluoromethyl,
R7B is hydrogen or (C1-C4) alkyl,
Q is CH or N,
R1 is (C1-C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl or (C3-C7) cycloalkyl,
where (C1-C6) alkyl, (C2-C6) alkenyl and (C2-C6) alkynyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of deuterium, halogen, cyano, oxo, hydroxyl, trifluoromethyl, (C3-C7) cycloalkyl, (C1-C6) alkoxy, trifluoromethoxy and phenyl,
in which (C3-C7) cycloalkyl may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of (C1-C4) alkyl, oxo, hydroxyl, (C1-C4) alkoxy and amino,
and
in which (C1-C6) alkoxy may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of amino, hydroxyl, (C1-C4) alkoxy, hydroxycarbonyl and (C1-C4) alkoxycarbonyl,
and
in which phenyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of halogen, cyano, nitro, (C1-C4) alkyl, trifluoromethyl, hydroxyl, hydroxymethyl, (C1-C4) alkoxy, trifluoromethoxy, (C1-C4) alkoxymethyl, hydroxycarbonyl, (C1-C4) alkoxycarbonyl, aminocarbonyl, mono-(C1-C4) alkylaminocarbonyl and di-(C1-C4) alkylaminocarbonyl,
and
where (C3-C7) cycloalkyl may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of fluorine, (C1-C4) alkyl, (C1-C4) alkoxy, hydroxy, amino and oxo,
R2 is benzothienyl, phenyl, thienyl or furyl,
where benzothienyl, phenyl, thienyl and furyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of halogen, cyano, nitro, (C1-C4) alkyl, trifluoromethyl, hydroxyl, (C1-C4) alkoxy and trifluoromethoxy,
R3 is trifluoromethyl, hydroxyl, trifluoromethoxy, (C1-C4) alkoxy, (C3-C7) cycloalkoxy, nitro, amino, —NR8—C(═O)—R9, —NR10—SO2—R11, —SO2—NR12R13, —O—C(═O)—NR14R15, —NR16—C(═O)—NR17R18, —NR19—C(═O)—OR20, —S(═O)nR21, —O—SO2—NR24R25, —NR26—SO2—NR27R28 or —NR30R31,
where
R8 is hydrogen or (C1-C4) alkyl,
R9 is hydrogen, (C1-C4) alkyl or (C3-C7) cycloalkyl,
or
R8 and R9 together with the atoms to which they are attached form a 5- to 7-membered heterocycle,
where the 5- to 7-membered heterocycle may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of fluorine, (C1-C4) alkyl and trifluoromethyl,
R10 is hydrogen or (C1-C4) alkyl,
R11 is (C1-C4) alkyl or (C3-C7) cycloalkyl,
or
R10 and R11 together with the atoms to which they are attached form a 5- to 7-membered heterocycle,
where the 5- to 7-membered heterocycle may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of fluorine, (C1-C4) alkyl and trifluoromethyl,
R12 is hydrogen, (C1-C4) alkyl or (C3-C7) cycloalkyl,
R13 is hydrogen, (C1-C4) alkyl or (C3-C7) cycloalkyl,
or
R12 and R13 together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycle,
where the 4- to 7-membered heterocycle may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of fluorine, oxo, hydroxyl, (C1-C4) alkyl and trifluoromethyl,
R14 is hydrogen, (C1-C4) alkyl or (C3-C7) cycloalkyl,
R15 is hydrogen, (C1-C4) alkyl or (C3-C7) cycloalkyl,
or
R14 and R15 together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycle,
where the 4- to 7-membered heterocycle may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of fluorine, oxo, hydroxyl, (C1-C4) alkyl and trifluoromethyl,
R16 is hydrogen or (C1-C4) alkyl,
R17 is hydrogen, (C1-C4) alkyl or (C3-C7) cycloalkyl,
R18 is hydrogen, (C1-C4) alkyl or (C3-C7) cycloalkyl,
or
R16 and R17 together with the nitrogen atoms to which they are attached form a 5- to 7-membered heterocycle,
where the 5- to 7-membered heterocycle may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of fluorine, trifluoromethyl and (C1-C4) alkyl,
or
R17 and R18 together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycle,
where the 4- to 7-membered heterocycle may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of fluorine, oxo, hydroxyl, (C1-C4) alkyl and trifluoromethyl,
R19 is hydrogen or (C1-C4) alkyl,
R20 is (C1-C4) alkyl or (C3-C7) cycloalkyl,
or
R19 and R20 together with the atoms to which they are attached form a 5- to 7-membered heterocycle,
where the 5- to 7-membered heterocycle may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of fluorine, (C1-C4) alkyl and trifluoromethyl,
n is a number 0, 1 or 2,
R21 is hydrogen, (C1-C4) alkyl or (C3-C7) cycloalkyl,
R24 is hydrogen, (C1-C4) alkyl or (C3-C7) cycloalkyl,
R25 is hydrogen, (C1-C4) alkyl or (C3-C7) cycloalkyl,
or
R24 and R25 together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycle,
where the 4- to 7-membered heterocycle may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of fluorine, oxo, hydroxyl, (C1-C4) alkyl and trifluoromethyl,
R26 is hydrogen or (C1-C4) alkyl,
R27 is hydrogen, (C1-C4) alkyl or (C3-C7) cycloalkyl,
R28 is hydrogen, (C1-C4) alkyl or (C3-C7) cycloalkyl,
or
R26 and R27 together with the nitrogen atoms to which they are attached form a 5- to 7-membered heterocycle,
where the 5- to 7-membered heterocycle may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of fluorine, trifluoromethyl and (C1-C4) alkyl,
or
R27 and R28 together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycle,
where the 4- to 7-membered heterocycle may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of fluorine, oxo, hydroxyl and (C1-C4) alkyl,
R30 is hydrogen, (C1-C4) alkyl or (C3-C7) cycloalkyl,
R31 is (C1-C4) alkyl or (C3-C7) cycloalkyl,
or
R30 and R31 together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycle,
where the 4- to 7-membered heterocycle may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of fluorine, oxo, hydroxyl, (C1-C4) alkyl and trifluoromethyl,
R4 is phenyl, naphthyl or 5- to 10-membered heteroaryl,
where phenyl, naphthyl and 5- to 10-membered heteroaryl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of halogen, cyano, nitro, (C1-C4) alkyl, difluoromethyl, trifluoro-methyl, hydroxyl, (C1-C4) alkoxy, difluoromethoxy and trifluoromethoxy,
R5 is hydrogen, deuterium, trifluoromethyl or (C1-C4) alkyl,
R29 is hydrogen or (C1-C4) alkyl,
or a salt thereof.

79 more elements

Substituted 2-acetamido-5-aryl-1,2,4-triazolones and use thereof

Life of this patent

Substituted 2-acetamido-5-aryl-1,2,4-triazolones and use thereof

Life of this patent

Abstract

Claims12