Methods for treating heart failure, thromboembolic disorders, and pulmonary fibrosis
This invention relates to methods for treating heart failure, thromboembolic disorders, and pulmonary fibrosis, comprising administering an effective amount of a compound of formula (I) in which the several variables are as defined in the specification and claims.
1. A method for treating a cardiovascular disorder selected from the group consisting of heart failure and thromboembolic disorders, comprising administering an effective amount of a compound of formula (I)
in which
R 1 is located in the meta- or para-position to the radical W and represents a radical selected from the group consisting of H, halogen and OCF 3 ;
R 2 represents H or halogen;
R 3 represents H or halogen;
R 4 represents C 1-6 -alkyl, C 3-8 -cycloalkyl, CF 3 , OCF 3 , F, Cl, OMe or phenyl, where the phenyl radical may additionally carry a substituent selected from the group consisting of halogen, CN, C 1-6 -alkoxy, CF 3 and C 1-6 -alkyl;
V is located in the ortho- or meta-position to the radical W and represents O, CH 2 O, OCF 2 or O—C 1-6 -alkyl-O; and
W represents CH 2 or CH 2 CH 2 ;
or a pharmaceutically acceptable salt or stereoisomer thereof.
2. A method for treating pulmonary fibrosis comprising administering an effective amount of a compound of formula (I)
in which
R 1 is located in the meta- or para-position to the radical W and represents a radical selected from the group consisting of H, halogen and OCF 3 ;
R 2 represents H or halogen;
R 3 represents H or halogen;
R 4 represents C 1-6 -alkyl, C 3-8 -cycloalkyl, CF 3 , OCF 3 , F, Cl, OMe or phenyl, where the phenyl radical may additionally carry a substituent selected from the group consisting of halogen, CN, C 1-6 -alkoxy, CF 3 and C 1-6 -alkyl;
V is located in the ortho- or meta-position to the radical W and represents O, CH 2 O, OCF 2 or O—C 1-6 -alkyl-O;
W represents CH 2 or CH 2 CH 2 ;
or a pharmaceutically acceptable salt or stereoisomer thereof.
3. The method of claim 1 , wherein in formula I
R 1 is located in the meta-position to the radical W and represents a radical selected from the group consisting of H and halogen; and
R 4 represents C 1-6 -alkyl, C 3-8 -cycloalkyl or phenyl, where the phenyl radical may additionally carry a substituent selected from the group consisting of halogen, CN, C 1-6 -alkoxy, CF 3 , and C 1-6 -alkyl.
4. The method of claim 1 , wherein in formula I
R 1 is located in the meta-position to the radical W and represents a radical selected from the group consisting of H, F, Cl and Br;
R 2 represents H,
R 3 represents H; and
R 4 represents methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl, where the phenyl radical may additionally carry a substituent selected from the group consisting of F, Cl, Br, CN, methoxy, ethoxy, n-propoxy, i-propoxy, n-butyloxy, i-butyloxy, t-butyloxy, CF 3 , methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, and t-butyl.
5. The method of claim 1 , wherein in formula I
R 1 is located in the meta-position to the radical W and represents H;
R 2 represents H;
R 3 represents H;
R 4 represents cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl, where the phenyl radical may additionally carry a substituent selected from the group consisting of F, Cl, Br, and CF 3 ;
V is located in the meta-position to the radical W and represents O; and
W represents CH 2 .
6. The method of claim 1 , wherein in formula I
R 1 is located in the meta-position to the radical W and represents H;
R 2 represents H;
R 3 represents H;
R 4 represents phenyl, where the phenyl radical may additionally carry a substituent selected from the group consisting of F, Cl, Br, OMe, CF 3 , methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, and t-butyl;
V is located in the ortho-position to the radical W and represents OCF 2 ; and
W represents CH 2 CH 2 .
7. The method of claim 1 , wherein in formula I
R 1 is located in the meta-position to the radical W and represents a radical selected from the group consisting of H, F, Cl and Br;
R 2 represents H;
R 3 represents H;
R 4 represents methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl, where the phenyl radical may additionally carry a substituent selected from the group consisting of F, Cl, Br, CN, OMe, OF 3 , methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, and t-butyl;
V is located in the ortho-position to the radical W and represents CH 2 O; and
W represents CH 2 CH 2 .
8. The method of claim 2 , wherein in formula I
R 1 is located in the meta-position to the radical W and represents a radical selected from the group consisting of H and halogen; and
R 4 represents C 1-6 -alkyl, C 3-8 -cycloalkyl or phenyl, where the phenyl radical may additionally carry a substituent selected from the group consisting of halogen, CN, C 1-6 -alkoxy, CF 3 , and C 1-6 -alkyl.
9. The method of claim 2 , wherein in formula I
R 1 is located in the meta-position to the radical W and represents a radical selected from the group consisting of H, F, Cl and Br;
R 2 represents H,
R 3 represents H; and
R 4 represents methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl, where the phenyl radical may additionally carry a substituent selected from the group consisting of F, Cl, Br, CN, methoxy, ethoxy, n-propoxy, i-propoxy, n-butyloxy, i-butyloxy, t-butyloxy, CF 3 , methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, and t-butyl.
10. The method of claim 2 , wherein in formula I
R 1 is located in the meta-position to the radical W and represents H;
R 2 represents H;
R 3 represents H;
R 4 represents cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or phenyl, where the phenyl radical may additionally carry a substituent selected from the group consisting of F, Cl, Br, and CF 3 ;
V is located in the meta-position to the radical W and represents O; and
W represents CH 2 .
11. The method of claim 2 , wherein in formula I
R 1 is located in the meta-position to the radical W and represents H;
R 2 represents H;
R 3 represents H;
R 4 represents phenyl, where the phenyl radical may additionally carry a substituent selected from the group consisting of F, Cl, Br, OMe, CE 3 , methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, and t-butyl;
V is located in the ortho-position to the radical W and represents OCF 2 ; and
W represents CH 2 CH 2 .
12. The method of claim 2 , wherein in formula I
R 1 is located in the meta-position to the radical W and represents a radical from the group consisting of H, F, Cl and Br;
R 2 represents H;
R 3 represents H;
R 4 represents methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or phenyl, where the phenyl radical may additionally carry a substituent selected from the group consisting of F, Cl, Br, CN, OMe, CF 3 , methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, and t-butyl;
V is located in the ortho-position to the radical W and represents CH 2 O; and
W represents CH 2 CH 2 .