Benzofuran oxyethylamines as antidepressants and anxiolytics
View Patent ↗Novel benzofuranoxyethylamines of the formula (I), in which R 1 , R 2 , R 3 , R 4 , m and n have the meanings indicated in Patent Claim ( 1 ), which have a strong affinity to the 5 HT 1A receptors and/or 5HT 1D receptors. The compounds inhibit serotonin reuptake, exhibit serotonin-agonistic and -antagonistic properties and are suitable as antidepressants, anxiolytics, antipsychotics, neuroleptics and/or antihypertonics.
1. A compound of formula I
in which
R 1 denotes mono- or disubstitution by OH, OA, CN, Hal, COR or CH 2 R,
R denotes OH, OA, NH 2 , NHA or NA 2 ,
R 2 , R 3 denote H or A,
R 4 denotes H, mono- or disubstitution by OH, OA, NH 2 , NHA, NA 2 , CN, Hal, COR or CH 2 R,
A denotes alkyl having 1, 2, 3, 4, 5 or 6 atoms,
Hal denotes F, Cl, Br or I,
m denotes 2, 3, 4, 5 or 6, and
n denotes 1, 2, 3 or 4,
or a pharmaceutically acceptable derivative, solvate or stereoisomer thereof.
2. A compound according to claim 1 , in which R 1 denotes CN or F, and R denotes NH 2 , OH, O-methyl or O-ethyl.
3. A compound according to claim 1 , in which R 2 denotes H or methyl, and R 3 denotes H or methyl.
4. A compound according to claim 1 , in which A denotes methyl or ethyl.
5. A compound according to claim 1 , in which R 4 denotes CONH 2 , COOC 2 H 5 or CONHA.
6. A compound according to claim 1 , in which m denotes 2 or 3, and n denotes 2 or 4.
7. A compound according to claim 1 , which is
4-{2-[4-(5-cyano-1H-indol-3-yl)butylamino]ethoxy}benzofuran-2-carboxylic acid methyl ester,
5-{2-[4-(5-cyano-1H-indol-3-yl)butylamino]ethoxy}benzofuran-2-carboxylic acid ethyl ester,
6-{2-[4-(5-cyano-1H-indol-3-yl)butylamino]ethoxy}benzofuran-2-carboxylic acid ethyl ester,
4-{2-[4-(5-cyano-1H-indol-3-yl)butylamino]ethoxy}benzofuran-2-carboxylic acid amide,
7-{2-[4-(5-cyano-1H-indol-3-yl)butylamino]ethoxy}benzofuran-2-carboxylic acid ethyl ester,
7-{2-[4-(5-cyano-1H-indol-3-yl)butylamino]ethoxy}benzofuran-2-carboxylic acid methyl ester,
7-{2-[4-(5-cyano-1H-indol-3-yl)butylamino]ethoxy}benzofuran-2-carboxylic acid amide,
7-{2-[4-(5-cyano-1H-indol-3-yl)butylamino]ethoxy}benzofuran-2-carboxylic acid,
5-{2-[4-(5-cyano-1H-indol-3-yl)butylamino]ethoxy}benzofuran-2-carboxylic acid amide,
5-{2-[2-(5-fluoro-1H-indol-3-yl)ethylamino]ethoxy}benzofuran-2-carboxylic acid amide,
6-{2-[4-(5-cyano-1H-indol-3-yl)butylamino]ethoxy}benzofuran-2-carboxylic acid amide,
5-bromo-7-{2-[4-(5-cyano-1H-indol-3-yl)butylamino]ethoxy}benzofuran-2-carboxylic acid methyl ester,
5-bromo-7-{2-[4-(5-cyano-1H-indol-3-yl)butylamino]ethoxy}benzofuran-2-carboxylic acid amide,
7-{2-[2-(5-fluoro-1H-indol-3-yl)ethylamino]ethoxy}benzofuran-2-carboxylic acid amide,
7-{2-[4-(5-cyano-1H-indol-3-yl)butylamino]ethoxy}-5-nitrobenzofuran-2-carboxylic acid amide,
7-{2-[2-(5-cyano-1H-indol-3-yl)ethylamino]ethoxy}benzofuran-2-carboxylic acid amide,
7-{3-[2-(5-cyano-1H-indol-3-yl)ethylamino]propoxy}benzofuran-2-carboxylic acid amide, or
7-{3-[2-(5-fluoro-1H-indol-3-yl)ethylamino]propoxy}benzofuran-2-carboxylic acid amide.
8. A process for preparing a compound of formula I according to claim 1 , comprising reacting a compound of formula II
in which
R 1 , R 4 , Hal and m have the meanings indicated for the compound of formula I, with a compound of formula III
in which
R 1 , R 2 R 3 and n have the meanings indicated for the compound of formula I,
and optionally a basic or acidic compound of formula I is converted into one of its salts or solvates by treatment with an acid or base.
9. A pharmaceutical composition, comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.
10. A compound according to claim 1 , wherein the pharmaceutically acceptable derivative of a compound of formula I is a pharmaceutically acceptable salt of a compound of formula I.
11. A compound according to claim 1 , which is an isolated stereoisomer of a compound of formula I.
12. A compound according to claim 1 , which is a basic or acidic compound of formula I.
13. A pharmaceutical composition, comprising a compound according to claim 7 and a pharmaceutically acceptable carrier.