Pyrazolopyridine, indazole, imidazopyridine, imidazopyrimidine, pyrazolopyrazine and pyrazolopyridine derivatives as stimulators of guanylate cyclase for cardiovascular disorders
View Patent ↗The present application relates to novel azabicyclic compounds, processes for their preparation, their use alone or in combinations for the treatment and/or prevention of diseases, and their use for producing medicaments for the treatment and/or prevention of diseases, especially for the treatment and/or prevention of cardiovascular disorders.
1. A compound of formula (I)
in which
L is phenyl which may be substituted up to twice by fluorine,
M is a bicyclic heteroaryl group of the formula (a-3), (b-3) or (c-3)
in which
* is the point of linkage to the —CH 2 -L group,
** is the point of linkage to the Q group,
and
A and E are independently of one another CH or N,
and
Q is a group of the formula
in which
# is the point of linkage to the M group,
J is CR 7 or N,
R 5 and R 6 are independently of one another hydrogen or amino,
R 7 is hydrogen, fluorine, chlorine, bromine, (C 1 -C 4 )-alkyl, (C 3 -C 6 )— cycloalkyl, pyridyl or —NR 12 R 13 , in which
R 12 is hydrogen or (C 1 -C 4 )-alkyl which may be substituted by hydroxy, methoxy or up to three times by fluorine,
R 13 is hydrogen, (C 1 -C 4 )-alkyl which may be substituted by hydroxy, methoxy or up to three times by fluorine, or (C 1 -C 4 )-acyl, (C 1 -C 4 )-alkoxycarbonyl or mono- or di-(C 1 -C 4 )-alkylaminocarbonyl,
or
R 12 and R 13 together with the nitrogen atom to which they are bonded form a 5- to 7-membered heterocycle which may be substituted by oxo,
and
R 8 is hydrogen or (C 1 -C 4 )-alkyl which may be substituted up to three times by fluorine,
or N-oxides, salts, or salts of the N-oxides thereof.
2. The compound of claim 1 , selected from the group consisting of:
6-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]-1,3,5-triazine-2,4-diamine;
6-[3-(2-fluorobenzyl)-1H-indazol-1-yl]-1,3,5-triazine-2,4-diamine;
6-[3-(2-fluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-1,3,5-triazine-2,4-diamine;
6-[8-(2-fluorobenzyl)imidazo[1,5-a]pyrimidin-6-yl]-1,3,5-triazine-2,4-diamine;
6-[3-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-1-yl]-1,3,5-triazine-2,4-diamine;
6-[3-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyrazin-1-yl]-1,3,5-triazine-2,4-diamine;
2-[8-(2-fluorobenzyl)imidazo[1,5-a]pyrimidin-6-yl]pyrimidine-4,6-diamine;
2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidine-4,5,6-triamine;
methyl {4,6-diamino-2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidin-5-yl}carbamate;
5-[3-(2-fluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-1,3,4-oxadiazol-2(3H)-one;
and
3-(2-fluorobenzyl)-1-(1H-tetrazol-5-yl)imidazo[1,5-a]pyridine
or N-oxides, salts, or salts of the N-oxides thereof.
3. A pharmaceutical composition comprising a compound of claim 1 in combination with an inert, non-toxic, pharmaceutically suitable excipient.
4. The pharmaceutical composition of claim 3 , further comprising an active ingredient selected from the group consisting of an organic nitrate, a NO donor, a cGMP-PDE inhibitor, an agent having antithrombotic activity, an agent for lowering blood pressure, and an agent for altering lipid metabolism.