Indole derivatives as serotonin reuptake inhibitors
Compounds of the formula (I), the use thereof for the preparation of a medicament for the treatment of diseases associated with the serotonin receptor and/or serotonin reuptake, in particular for the preparation of a medicament as anxiolytic, antidepressant, neuroleptic and/or antihypertonic and/or for positively influencing obsessive-compulsive disorder (OCD), sleeping disorders, tardive dyskinesia, learning disorders, age-dependent memory disorders, eating disorders, such as bulimia, and/or sexual dysfunctions. The compounds bind to the 5-HT 1A receptor.
1. Compounds of the formula I
in which
X=N or CH,
R 1 , R 2 , R 3 =independently of one another OH, OA, CN, Hal, COR 4 or CH 2 R 4 ,
R 4 =OH, OA, NH 2 , NHB or NB 2 ,
Q=CH 2 or CO,
A, B=independently of one another straight-chain or branched alkyl or alkoxy having 1 to 10 C atoms, alkenyl having 2 to 10 C atoms or alkoxyalkyl having 2 to 10 C atoms,
m=2, 3, 4, 5 or 6 and
n=0, 1, 2, 3 or 4,
or physiologically acceptable salts or stereoisomers thereof, including mixtures thereof in all ratios.
2. Compounds according to claim 1 in which
X=N,
R 1 , R 2 , R 3 =independently of one another CN, OH, COR 4 or CH 2 R 4 ,
R 4 =OH, NH 2 , NHB or NHB 2 ,
Q=CH 2 or CO,
B=alkyl having 1-6 C atoms,
m=4 and
n=0,
or physiologically acceptable salts or stereoisomers thereof, including mixtures thereof in all ratios.
3. A compound of the formula
a) 5-{4-[4-(5-cyano-2,3-dihydro-1H-indol-3-yl)butyl]piperazin-1-yl}benzo-furan-2-carboxamide
b) 5-{4-[4-(5-cyano-2-oxo-2,3-dihydro-1H-indol-3-yl)butyl]piperazin-1-yl}-benzofuran-2-carboxamide
or
c) 5-{4-(5-fluoro-2-oxo-2,3-dihydro-1H-indol-3-yl)butyl]piperazin-1-yl)-benzofuran-2-carboxamide or
4. Process for the preparation of compounds according to claim 1 or physiologically acceptable salts or stereoisomers thereof, comprising
a) reacting a compound of the formula II, in which R 1 , R 2 , R 3 , X, m and n have the meanings indicated in claim 1 ,
with dimethyl sulfoxide and concentrated HCl, or
b) reacting a compound of the formula III, in which R 1 , R 2 , and n have the meanings indicated in claim 1 , and Y is a halogen or an alcohol provided with protecting groups,
with trifluoroacetic acid and triethylsilane and subsequently coupling with a compound of the formula IV, in which R 3 , X and n have the meanings indicated in claim 1
and reacting with dimethyl sulfoxide and concentrated HCl or
c) reacting a compound of the formula V, in which R 2 and m have the meanings indicated in claim 1 and Y is a halogen, or an alcohol provided with protecting groups,
with a dehydrating reagent and subsequently coupling with a compound of the formula IV, and reacting with dimethyl sulfoxide and concentrated HCl.
5. Pharmaceutical composition comprising at least one compound according to claim 1 and/or physiologically acceptable salts or stereoisomers thereof, including mixtures thereof in all ratios, and a pharmaceutically acceptable carrier.
6. Pharmaceutical composition, according to claim 5 comprising further excipients and/or adjuvants.
7. Process for the preparation of a pharmaceutical composition, comprising bringing a compound according to claim 1 and/or one of its physiologically acceptable salts or stereoisomers, including mixtures thereof in all ratios, into a suitable dosage form together with a solid, liquid or semi-liquid excipient or adjuvant.
8. A method of achieving an anxiolytic, antidepressant, neuroleptic and/or antihypertonic effect and for treating migraine or obsessive compulsive disorder, comprising administering to a host in need thereof an effective amount of a compound according to claim 1 and/or physiologically acceptable salts or stereoisomers thereof, including mixtures thereof in all ratios.