Substituted triazole derivatives and uses thereof

Patent metadata

Field	Value
Publication number	US-11173151-B2
Application number	US-201816756623-A
Country	US
Kind code	B2
Filing date	Oct 17, 2018
Priority date	Oct 24, 2017
Publication date	Nov 16, 2021
Grant date	Nov 16, 2021

Abstract

The present invention relates to novel substituted 1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.

First claim

The invention claimed is:

1. A compound of general formula (I)

in which
R 1 represents hydrogen, 1,1-dioxidothiomorpholin-4-yl, 3-oxopiperazin-1-yl, (1,1-dioxidothiomorpholin-4-yl)carbonyl, (3-oxopiperazin-1-yl)carbonyl or 2-amino-2-methyl-propylaminocarbonyl,
R 2 represents a group of formula

in which
# represents the point of attachment to the 1,2,4-triazolyl-ring,
R 4 represents hydrogen,
R 5 represents C 1 -C 5 -alkyl or C 3 -C 6 -cycloalkyl,
where alkyl may be substituted by 1 to 2 substituents independently of one another selected from the group consisting of fluorine, hydroxy, amino, hydroxycarbonyl, aminocarbonyl, trifluoromethyl, C 3 -C 6 -cycloalkyl, 4- to 7-membered heterocyclyl and C 1 -C 4 -alkoxycarbonyl,
wherein cycloalkyl may be substituted by one substituent hydroxy and amino,
and
wherein heterocyclyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of oxo, chlorine, fluorine, hydroxy, aminocarbonyl, trifluoromethyl, methyl and methoxy,

where cycloalkyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of fluorine, cyano, hydroxy, amino, trifluoromethyl and methyl,

or
R 4 and R 5 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl,
where heterocyclyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of oxo, chlorine, fluorine, hydroxy, aminocarbonyl, trifluoromethyl, methyl, methoxy and methoxymethyl,

R 6 represents hydrogen,
R 7 represents C 1 -C 5 -alkyl or C 3 -C 6 -cycloalkyl,
where alkyl may be substituted by 1 to 2 substituents independently of one another selected from the group consisting of fluorine, hydroxy, amino, hydroxycarbonyl, aminocarbonyl, trifluoromethyl, C 3 -C 6 -cycloalkyl, 4- to 7-membered heterocyclyl and C 1 -C 4 -alkoxycarbonyl,
wherein cycloalkyl may be substituted by one substituent hydroxy and amino,
and
wherein heterocyclyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of oxo, chlorine, fluorine, hydroxy, aminocarbonyl, trifluoromethyl, methyl and methoxy,

where cycloalkyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of fluorine, cyano, hydroxy, amino, trifluoromethyl and methyl,

or
R 6 and R 7 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl,
where heterocyclyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of oxo, chlorine, fluorine, hydroxy, aminocarbonyl, trifluoromethyl, methyl, methoxy and methoxymethyl,

R 8 represents hydrogen,
R 9 represents C 1 -C 5 -alkyl or C 3 -C 6 -cycloalkyl,
where alkyl may be substituted by 1 to 2 substituents independently of one another selected from the group consisting of fluorine, hydroxy, amino, hydroxycarbonyl, aminocarbonyl, trifluoromethyl, C 3 -C 6 -cycloalkyl, 4- to 7-membered heterocyclyl and C 1 -C 4 -alkoxycarbonyl,
wherein cycloalkyl may be substituted by one substituent fluorine, hydroxy and amino,
and
wherein heterocyclyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of oxo, chlorine, fluorine, hydroxy, aminocarbonyl, trifluoromethyl, methyl and methoxy,

where cycloalkyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of fluorine, cyano, hydroxy, amino, trifluoromethyl and methyl,

or
R 8 and R 9 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl,
where heterocyclyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of oxo, chlorine, fluorine, hydroxy, aminocarbonyl, trifluoromethyl, methyl, methoxy and methoxymethyl,

R 10 represents hydrogen, methyl, ethyl or propan-2-yl,
R 11 represents C 1 -C 5 -alkyl, prop-2-en-1-yl, 3-methylbut-2-en-1-yl, methoxy, C 3 -C 7 -cycloalkyl, phenyl, 4- to 6-membered heterocyclyl or 5- or 6-membered heteroaryl,
where alkyl may be substituted by 1 to 2 substituents independently of one another selected from the group consisting of fluorine, cyano, hydroxy, amino, aminocarbonyl, trifluoromethyl, 1,1,2,2-tetrafluoroethyl, C 3 -C 6 -cycloalkyl, phenyl, 4- to 7-membered heterocyclyl, 5- or 6-membered heteroaryl and C 1 -C 4 -alkoxycarbonyl,
wherein cycloalkyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of fluorine, cyano, hydroxyl and methyl,
and
wherein phenyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of fluorine, cyano, hydroxyl and methyl,
and
wherein heterocyclyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of oxo, chlorine, fluorine, hydroxy, aminocarbonyl, trifluoromethyl, methyl and methoxy,
and
wherein heteroaryl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of fluorine, trifluoromethyl and methyl,

where cycloalkyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of fluorine, cyano, hydroxy, amino and methyl,
and
where phenyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of chlorine, fluorine, cyano, hydroxy, amino and methyl,
and
where heterocyclyl may be substituted by 1 to 3 substituents of oxo,
and
where heteroaryl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of chlorine, fluorine, hydroxy, amino, trifluoromethyl, methyl and ethyl,

or
R 10 and R 11 together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocyclyl, 6-oxo-2,5,7-triazaspiro[3.4]octan-2-yl, 2-oxa-5-azabicyclo[2.2.1]hept-5-yl or 5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl,
where heterocyclyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of oxo, chlorine, fluorine, hydroxy, formyl, aminocarbonyl, trifluoromethyl, methyl, ethyl, methoxy, methoxymethyl, dimethylamino and methylcarbonylamino,

R 12 represents hydrogen, chlorine or fluorine,
R 13 represents methyl, methoxy or C 3 -C 6 -cycloalkyl,
where methyl and methoxy may be substituted by one substituent independently of one another selected from the group consisting of fluorine, hydroxy, trifluoromethyl, methoxy, C 3 -C 6 -cycloalkyl, 4- to 7-membered heterocyclyl, methylsulfonyl and methylsulfonylamino,
and
where cycloalkyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of fluorine and trifluoromethyl,

R 14 represents trifluoromethyl, methyl, methoxy, 2,2,2-trifluoroethylamino, C 3 -C 6 -cycloalkyl or 4- to 6-membered heterocyclyl,
where methyl and methoxy may be substituted by one substituent independently of one another selected from the group consisting of fluorine, hydroxy, trifluoromethyl, methoxy, C 3 -C 6 -cycloalkyl, 4- to 7-membered heterocyclyl, methylsulfonyl and methylsulfonylamino,
and
where cycloalkyl may be substituted by 1 to 3 substituents independently of one another select

Assignees

• Bayer Ag
• Bayer Pharma AG

Inventors

• Collin-Kroepelin Marie-Pierre
• Kolkhof Peter
• Neubauer Thomas
• Fuerstner Chantal
• Pook Elisabeth
• Wittwer Matthias Beat
• Lustig Klemens
• Tinel Hanna
• Lindner Niels
• Schirmer Heiko

Classifications

• C07D409/14

  containing three or more hetero rings · CPC title

• C07D487/10

  Spiro-condensed systems · CPC title

• A61K31/4439 Primary

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• A61P13/00

  Drugs for disorders of the urinary system · CPC title