Amide-substituted phenyltriazole derivatives and uses thereof

Patent metadata

Field	Value
Publication number	US-10815205-B2
Application number	US-201716098266-A
Country	US
Kind code	B2
Filing date	May 2, 2017
Priority date	May 3, 2016
Publication date	Oct 27, 2020
Grant date	Oct 27, 2020

Abstract

The present invention relates to novel 5-(carboxamide)-1-phenyl-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 a group of the formula

in which
# 1 represents the point of attachment to the nitrogen atom,

Ar represents a group of the formula

in which
# 2 represents the point of attachment to the nitrogen atom,
R 2 represents a group selected from trifluoromethyl, trifluoromethoxy, ethoxy, —C(═O)N(H)CH 3 and —S(═O) 2 CH 3 ,

or a pharmaceutically acceptable salt, hydrate and/or solvate thereof.

2. The compound of general formula (I) according to claim 1 , wherein
R 1 represents a group of the formula

in which
# 1 represents the point of attachment to the nitrogen atom,

R 2 represents a group selected from trifluoromethyl, trifluoromethoxy, ethoxy, —C(═O)N(H)CH 3 and —S(═O) 2 CH 3 ,
or a pharmaceutically acceptable salt, hydrate and/or solvate thereof.

3. The compound of general formula (I) according to claim 1 , wherein
R 1 represents a group of the formula

in which
# 1 represents the point of attachment to the nitrogen atom,

R 2 represents a group selected from trifluoromethyl and trifluoromethoxy,
or a pharmaceutically acceptable salt, hydrate and/or solvate thereof.

4. The compound as defined in claim 1 for use in a method for the treatment of
acute heart failure, or
chronic heart failure.

5. A pharmaceutical composition comprising a compound as defined in claim 1 and one or more pharmaceutically acceptable excipients.

6. The pharmaceutical composition as defined in claim 5 for the treatment of a disease selected from the group consisting of
acute heart failure, or
chronic heart failure.

7. A pharmaceutical composition comprising a compound of general formula (I) according to claim 1 and one or more further active ingredients.

8. The pharmaceutical composition of claim 7 wherein the one or more further active ingredients is selected from the group consisting of
diuretic,
angiotensin All antagonist,
ACE inhibitor,
beta-receptor blocker,
mineralocorticoid receptor antagonist,
antidiabetic,
organic nitrate,
NO donor,
activator, and
stimulator of the soluble guanylate cyclase,
antiinflammatory agents,
immunosuppressive agent,
phosphate binder, and
compound which modulate vitamin D metabolism.

9. A method for the treatment of a disease selected from the group consisting of
acute heart failure, or
chronic heart failure,

in a human or other mammal, comprising administering to a human or other mammal in need thereof a therapeutically effective amount of one or more compounds as defined in claim 1 .

10. A method for the treatment of a disease selected from the group consisting of
acute heart failure, or
chronic heart failure,

in a human or other mammal, comprising administering to a human or other mammal in need thereof a therapeutically effective amount of a pharmaceutical composition as defined in claim 5 .

11. A method of preparing a compound of general formula (I) according to claim 1 said method comprising the step
[A] of allowing an intermediate compound of formula (II):

in which R 1 is as defined for the compound of general formula (I) according to claim 1 ,
R 3 represents a (C 1 -C 4 )-alkyl group,

to react in a first step in the presence of a base with a compound of general formula (III):

in which
R 4 represents a (C 1 -C 4 )-alkyl group,

to give an intermediate compound, which is then allowed to react in the presence of a base in a second step with a hydrazine compound of general formula (IV) or a respective salt thereof

in which Ar is as defined for the compound of general formula (I) according to claim 1 , thereby giving a compound of general formula (V):

in which R 1 and Ar are as defined for the compound of general formula (I) according to claim 1 , and
R 4 represents a (C 1 -C 4 )-alkyl group,

followed by a subsequent step
[B] of allowing the compound of formula (V) obtained in step [A] to react with ammonia thereby giving a compound of general formula (I):

in which R 1 and Ar are as defined for the compound of general formula (I) according to claim 1 ,

optionally followed by step
[C] conversion of the alcohols of general formula (I-A):

in which Ar is as defined for the compound of general formula (I) according to claim 1 ,

to the ketones of general formula (I-B):

in which Ar is as defined for the compound of general formula (I) according to claim 1 ,

using known oxidation methods,
each [A], [B] and [C] optionally followed, where appropriate, by (i) separating the compounds of formula (I) thus obtained into their respective enantiomers, and/or (ii) converting the compounds of formula (I) into their respective hydrates, solvates, salts and/or hydrates or solvates of the salts by treatment with the corresponding solvents and/or acids or bases.

12. The method of claim 11 , wherein R 3 and R 4 are methyl.

13. The method of claim 11 , wherein R 3 or R 4 are methyl.

Assignees

• Bayer Pharma AG

Inventors

• Collin-Kröpelin Marie-Pierre
• Kolkhof Peter
• Neubauer Thomas
• Fürstner Chantal
• Pook Elisabeth
• Wittwer Matthias Beat
• Lustig Klemens
• Buchmüller Anja
• Tinel Hanna
• DRÖBNER Karoline
• Mondritzki Thomas
• Schirmer Heiko
• Kretschmer Axel
• Schmeck Carsten
• Wasnaire Pierre
• Cernecka Hana

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P13/12

  of the kidneys · CPC title

• A61K31/4196

  1,2,4-Triazoles · CPC title

• C07D249/14 Primary

  Nitrogen atoms · CPC title

• C07D403/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title