Bradykinin B2 receptor antagonists
The invention relates to a compound according to general formula (I), which acts as a bradykinin (BK) B2 receptor antagonist; to a pharmaceutical composition containing one or more of the compound(s) of the invention; to a combination preparation containing at least one compound of the invention and at least one further active pharmaceutical ingredient; and to uses of said compound(s), including the use as a medicament.
1. A compound of the general formula (I):
or a pharmaceutically acceptable salt thereof, wherein
A represents the group:
A 1 is N;
A 2 is N;
A 5 is N—R A5 ;
R A5 represents a hydrogen atom or a (C 1 -C 3 )alkyl group;
R 1 represents a (C 1 -C 2 )alkyl or (C 2 -C 4 )alkoxyalkyl group, which alkyl group or alkoxyalkyl group may be substituted by one or more, identical or different, group(s) selected from a deuterium atom, halogen atom, and OH;
R 2 represents a hydrogen atom or a deuterium atom;
R 3 represents a hydrogen atom or (C 1 -C 3 )alkyl;
E represents CR E1 R E2 R E3 or Hce;
Hce represents a monocyclic, partially unsaturated or aromatic heterocycle having 3 to 5 C atoms and 1 to 3 N atom(s) or 3 to 5 C atoms, 1-2 N atom(s) and 1 O atom; which heterocycle is unsubstituted or may be mono- or, disubstituted, at each occasion independently, by a halogen atom, OH, (C 1 -C 3 )alkyl, (C 1 -C 3 )haloalkyl, (C 1 -C 3 )alkoxy, (C 1 -C 3 )haloalkoxy or ═O;
R E1 and R E2 each, independently of one another, represents a hydrogen atom, halogen atom, or G;
R E3 represents a hydrogen atom, halogen atom, G, OG or OH; and
G represents a (C 1 -C 6 )alkyl group in which 1 to 7 H atoms may be replaced by a halogen atom.
2. The compound, or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 1 represents CH 3 , CD 3 , CH 2 OH, CH 2 F, CHF 2 or CF 3 .
3. The compound, or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 1 represents CH 3 , CD 3 or CH 2 OH.
4. The compound, or a pharmaceutically acceptable salt thereof, according to claim 3 , wherein R 3 represents a hydrogen atom or a methyl group.
5. The compound, or a pharmaceutically acceptable salt thereof, according to claim 4 , wherein A represents the group
6. The compound, or a pharmaceutically acceptable salt thereof, according to claim 5 , wherein E represents
7. The compound, or a pharmaceutically acceptable salt thereof, according to claim 5 , wherein E represent
8. The compound, or a pharmaceutically acceptable salt thereof, according to claim 5 , wherein E represents
9. A pharmaceutical composition that comprises a compound, or a pharmaceutically acceptable salt thereof, according to claim 1 and at least one carrier substance, excipient or adjuvant.
10. The pharmaceutical composition according to claim 9 , wherein the pharmaceutical composition is formulated as an aerosol, a cream, a gel, a pill, a capsule, a syrup, a solution, a transdermal patch or a pharmaceutical delivery device.
11. A method of treating angioedema in a subject comprising administering to the subject with angioedema a compound, or a pharmaceutically acceptable salt thereof, according to claim 1 .
12. A compound having the following structure:
or a pharmaceutically acceptable salt thereof.
13. A pharmaceutical composition that comprises a compound, or a pharmaceutically acceptable salt thereof, according to claim 12 and at least one carrier substance, excipient or adjuvant.
14. The pharmaceutical composition according to claim 13 , wherein the pharmaceutical composition is formulated as an aerosol, a cream, a gel, a pill, a capsule, a syrup, a solution, a transdermal patch or a pharmaceutical delivery device.
15. A method of treating angioedema in a subject comprising administering to the subject with angioedema a compound, or a pharmaceutically acceptable salt thereof, according to claim 12 .