Carbamate-substituted pyrazolopyridines
View Patent ↗The present invention relates to compounds which stimulate soluble guanylate cyclase, to the preparation thereof and to the use thereof as medicaments, in particular as medicaments for the treatment of cardiovascular disorders and/or sexual dysfunction.
1. A compound of the formula (I)
in which
R 1 is —NR 3 C(═O)OR 4 ,
R 2 is hydrogen or NH 2 ,
R 3 is hydrogen or (C 1 –C 4 )-alkyl,
R 4 is (C 1 –C 6 )-alkyl,
or a salt or hydrate thereof.
2. The compound of claim 1 ,
in which
R 1 is —NR 3 C(═O)OR 4 ,
R 2 is hydrogen or NH 2 ,
R 3 is (C 1 –C 4 )-alkyl,
R 4 is (C 1 –C 4 )-alkyl,
or a salt or hydrate thereof.
3. The compound of claim 1 ,
in which
R 1 is —NR 3 C(═O)OR 4 ,
R 2 is NH 2 ,
R 3 is methyl or ethyl,
R 4 is methyl, ethyl or isopropyl,
or a salt or hydrate thereof.
4. The compound of claim 1 having the following structure:
methyl 4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl(methyl)carbamate
or a salt or hydrate thereof.
5. The compound of claim 1 , wherein said compound is methyl 4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinylcarbamate:
or a salt or hydrate thereof.
6. A process for the preparation of compounds of the formula (I) as defined in claim 1 , characterized in that either
[A] a compound of the formula (Ia)
in which
R 4 is as defined in claim 1 ,
is reacted with a compound of the formula (II)
R 3 —X 1 (II),
in which
R 3 is as defined in claim 1 , and
X 1 is a leaving group,
or
[B] the compound of the formula (III)
is reacted with a compound of the formula (IV)
in which
R 4 is as defined in claim 1 ,
or
[C] the compound of the formula (V)
is reacted with a compound of the formula (VI)
in which
R 3 and R 4 are as defined in claim 1 ,
to give a compound of the formula (Ib)
in which
R 3 and R 4 are as defined in claim 1 .
7. A pharmaceutical composition comprising at least one compound of the formula (I) as defined in claim 1 , and at least one further excipient.
8. A pharmaceutical composition comprising at least one compound of the formula (I) as defined in claim 1 in combination with at least one organic nitrate or NO donor.
9. A pharmaceutical composition comprising at least one compound of the formula (I) as defined in claim 1 in combination with at least one compound which inhibits the breakdown of cyclic guanosine monophosphate (cGMP).
10. A method for the treatment of hypertension, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 .
11. A method for the treatment of sexual dysfunction, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 .
12. The method of claim 10 or 11 , where compounds of the formula (I) as defined in claim 1 are employed in combination with at least one organic nitrate or NO donor or in combination with at least one compound which inhibits the breakdown of cyclic guanosine monophosphate (cGMP).
13. The method of claim 11 , wherein the sexual dysfunction is erectile dysfunction or female sexual dysfunction.