Difluorophenol derivatives and their use
View Patent ↗The present application relates to novel difluorophenol derivatives, processes for their preparation, their use for the treatment and/or prophylaxis of diseases, and their use for producing medicaments for the treatment and/or prophylaxis of diseases, especially for the treatment and/or prevention of cardiovascular disorders.
1. A compound of the formula (I)
in which
U, V and W together form a group of the formula *—CH═CH—CH<, *—CH 2 —CH 2 —CH< or *—CH 2 —CH 2 —N<, in which * means the point of linkage to the phenyl ring,
A is O or CH 2 ,
D is a bond or is (C 1 -C 7 )-alkanediyl, (C 2 -C 7 )-alkenediyl or (C 2 -C 7 )-alkynediyl, each of which may be substituted one or more times by fluorine,
E is hydrogen, trifluoromethyl or a group of the formula
in which ** means the point of linkage to the group D and
G is a bond, CH 2 , —CH 2 —CH 2 — or —CH═CH—,
X is —CH 2 —CH 2 — or a group of the formula
in which *** means the point of linkage to the group Y,
Y is carboxyl or a group of the formula
in which # means the respective point of linkage,
R 1 , R 2 , R 3 , R 4 and R 5 are independently of one another substituents selected from the series halogen, (C 1 -C 6 )-alkyl, trifluoromethyl, (C 1 -C 6 )-alkoxy, trifluoromethoxy, cyano and nitro, and
o, p, q, r and s are independently of one another each the number 0, 1, 2, 3 or 4, where in the case where R 1 , R 2 , R 3 , R 4 or R 5 occur more than once, their meanings may in each case be identical or different,
and salts thereof.
2. The compound of the formula (I) as claimed in claim 1 , in which
U, V and W together form a group of the fomula *—CH═CH—CH< or *—CH 2 —CH 2 —N< in which * means the point of linkage to the phenyl ring,
A is O,
D is (C 1 -C 7 )-alkanediyl which may be substituted one or more times by fluorine,
E is hydrogen, trifluoromethyl or is a group of the formula
in which ** means the point of linkage to the group D,
X is —CH 2 —CH 2 — or a group of the formula
in which *** means the point of linkage to the group Y,
Y is carboxyl or a group of the formula
in which # means the respective point of linkage, and
R 1 , R 2 , R 3 and R 4 are independently of one another a substituent selected from the series fluorine, chlorine, bromine, (C 1 -C 4 )-alkyl, trifluoromethyl, (C 1 -C 4 )-alkoxy and trifluoromethoxy,
o, p, q and r are independently of one another each the number 0, 1 or 2,
where in the case where R 1 , R 2 , R 3 or R 4 occur more than once, their meanings may in each case be identical or different,
R 5 is fluorine, and
s is the number 0 or 1,
and salts thereof.
3. A compound of the formula (I-A)
in which
D is (C 1 -C 7 )-alkanediyl which may be substituted one or more times by fluorine,
E is hydrogen, trifluoromethyl or is a group of the formula
in which ** means the point of linkage to the group D,
Y is carboxyl or a group of the formula
in which # means the point of linkage,
R 1 , R 2 , R 3 and R 4 are independently of one another a substituent selected from the series fluorine, chlorine, bromine, methyl, tent-butyl, trifluoromethyl and methoxy, and
o, p, q and r are independently of one another each the number 0, 1 or 2,
where in the case that R 1 , R 2 , R 3 or R 4 occur more than once, their meanings may in each case be identical or different,
and salts thereof.
4. A compound of the formula (I-B)
in which
D is (C 1 -C 7 )-alkanediyl which may be substituted one or more times by fluorine,
E is hydrogen, trifluoromethyl or is a group of the formula
in which ** means the point of linkage to the group D,
R 1 , R 2 , R 3 and R 4 are independently of one another a substituent selected from the series fluorine, chlorine, bromine, methyl, tert-butyl, trifluoromethyl and methoxy, and
o, p, q and r are independently of one another each the number 0, 1 or 2,
where in the case that R 1 , R 2 , R 3 or R 4 occur more than once, their meanings may in each case be identical or different,
and salts thereof.
5. A pharmaceutical composition comprising a compound as defined in claim 1 in combination with an inert, non-toxic, pharmaceutically suitable excipient.
6. The pharmaceutical composition of claim 5 further comprising an active ingredient selected from the group consisting of organic nitrates, NO donors, cGMP-PDE inhibitors, stimulators of guanylate cyclase, agents having antithrombotic activity, active ingredients which lower blood pressure, and active ingredients which modify lipid metabolism.