Sulfonate substituted pyrazol pyridine derivatives
View Patent ↗This invention relates to pyrazol pyridine derivatives of formula (I) wherein R 1 is a radical of the formula −O—SO 2 —R 3 in which R 3 is optionally substituted C 1—6 —alkyl, optionally substituted C 3—8 —cycloalkyl, or optionally substituted phenyl; R 2 is H, optionally substituted C 1—6 —alkyl —CO—or optionally substituted C 1—6 —alkyl—SO 2 — ; as well as salts, stereoisomers, tautomers, and hydrates thereof. Pharmaceutical compositions containing these materials and methods of using them in medical treatment are also described and claimed.
1. A compound of the formula (I)
in which
R 1 is a radical of the formula —O—SO 2 —R 3 ,
where
R 3 is a radical from the group consisting of optionally substituted C 1-6 -alkyl, optionally substituted C 3-8 -cycloalkyl, or optionally substituted phenyl;
R 2 is H, optionally substituted C 1-6 -alkyl-CO or optionally substituted C 1-6 -alkyl-SO 2 —;
or a salt, stereoisomer, tautomer or hydrate thereof.
2. The compound as claimed in claim 1 ,
in which
R 1 is a radical of the formula —O—SO 2 —R 3 ,
where
R 3 is a radical selected from the group consisting of C 1-6 -alkyl which is optionally substituted by one to three halogen radicals, and C 3-8 -cycloalkyl; and
R 2 is H, C 1-6 -alkyl-CO which is optionally substituted by one to three halogen radicals, or C 1-6 -alkyl-SO 2 — which is optionally substituted by one to three halogen radicals.
3. The compound as claimed in claim 1 ,
in which
R 1 is a radical of the formula —O—SO 2 —R 3 ,
where
R 3 is a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl, 1,1,1-trifluoro-4-n-butyl, chloromethyl and cyclopropyl; and
R 2 is H or CH 3 CO.
4. A process for preparing compounds of the formula I, comprising reacting a compound of the formula (II)
with a compound of the formula (III)
in an organic solvent in the presence of a base with heating and subsequent conversion of the ether group in the free hydroxyl group to give a compound of the formula (IV)
and subsequent reaction with a compound of the formula X—SO 2 —R 2
in which
X is a leaving group which can be replaced by a hydroxyl group; and
R 2 has the meaning indicated in claim 1 ;
in an organic solvent in the presence of a base with heating to give a compound of the formula (I).
5. A pharmaceutical composition comprising at least one compound of the formula (I) as claimed in claim 1 plus a pharmaceutically acceptable carrier.
6. A pharmaceutical composition comprising at least one compound of the formula (I) as claimed in claim 1 in combination with at least one organic nitrate or NO donor.
7. A pharmaceutical composition comprising at least one compound of the formula (I) as claimed in claim 1 in combination with at least one compound which inhibits the breakdown of cyclic guanosine monophosphate (cGMP).
8. A method for the treatment of hypertension comprising administering an effective amount of a compound of general formula (I) as claimed in claim 1 .
9. A method for the treatment of sexual dysfunction comprising administering an effective amount of a compound of general formula (I) as claimed in claim 1 .
10. The method as claimed in claim 8 or claim 9 , where the compound of the general formula (I) as claimed in claim 1 is 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).