3-phenyl-1-(4-piperidyl or 1,2,3,6-piperidyl)- indene compouds

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 211/08 (2006.01) C07D 211/12 (2006.01) C07D 211/14 (2006.01) C07D 211/18 (2006.01) C07D 211/20 (2006.01) C07D 211/22 (2006.01) C07D 211/24 (2006.01) C07D 211/34 (2006.01) C07D 211/70 (2006.01) C07D 213/30 (2006.01) C07D 401/06 (2006.01) C07D 413/06 (2006.01) C07D 417/06 (2006.01)

Patent

CA 1250297

ABSTRACT OF THE DISCLOSURE The present invention relates to novel phenylindene derivatives having interesting pharmacodynamic properties which make them useful as psychopharmacologicals in the treatment especially of psychoses such as schizophrenia, having a low degree of undesired side effects such as cataleptic effects, methods for the preparation of said phenylindene derivatives, pharmaceutical compositions containing same, and methods for the treatment of psychic disorders, such as psychoses and depressions and pain, by administering a therapeutically active amount of one of said derivatives to a living animal body, including human beings. The novel phenylindene derivatives of the present invention are represented by the following formula: Image I wherein the dotted lines indicate optional bonds; R1 is hydrogen, halogen, lower alkyl, lower alkoxy, hydroxymethyl, lower alkoxy- methyl, cyano, trifluoromethyl, lower alkylthio or lower alkylsulfonyl; R2 is halogen, lower alkyl or trifluoromethyl; and R3 is hydrogen, alkyl or alkenyl (straight or branched chain with C1-C6 inclusive) optionally substituted with one or two hydroxy groups, any hydroxy group present being optionally esterified with an aliphatic carboxylic acid having from two to twenty-four carbon atoms inclusive, or R3 is Image , wherein Z is NR4, 0 or S, where R4 is H or lower alkyl, and W is 0 or S, as well as pharmaceutically acceptable acid addition salts of the compounds of Formula 1. The novel phenylindene derivatives are potent dopaminergic antagonists both in and in vitro pharmacological tests as compared to classical neuroleptics. In addition, most of the indenes of Formula 1 are strong 5-HT antagonists both perifically and centrally, which might be a benefit in the treatment of psychic disorders or cardiovascular diseases.

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