Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
1995-12-22
1997-07-29
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
514650, 514657, 564339, 564391, 564428, 564440, A61K 3113, C07C32325, C07C31728
Patent
active
056522711
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP94/01494, filed May 7, 1994.
The present invention relates to novel therapeutic agents, to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of depression, anxiety, Parkinson's disease, obesity, cognitive disorders, seizures, neurological disorders such as epilepsy, and as neuroprotective agents to protect against conditions such as stroke.
The present invention provides compounds of formula I ##STR3## and pharmaceutically acceptable salts thereof in which m is 0, 1 or 2; ##STR4## in which R.sub.5 is H or an alkyl group containing 1 to 4 carbon atoms; Y is an alkylene chain containing 1 or 2 carbon atoms optionally substituted by one or more alkyl groups containing 1 to 3 carbon atoms; substituted by one or more alkyl groups containing 1 to 3 carbon atoms; are the same or different (for example fluoro, chloro, bromo or iodo) or R is naphthyl; and branched chain alkyl group containing 1 to 4 carbon atoms, an arylalkyl group in which the alkyl group contains 1 to 3 carbon atoms, provided that when R.sub.1 is benzyl, R.sub.2 is H or methyl.
In preferred compounds of formula I, m is 0, 1 or 2 and n is 3 or 4.
In preferred compounds of formula I, X is carbonyl or a group of formula II in which R.sub.5 is H.
In preferred compounds of formula I, Y is methylene.
In preferred compounds of formula I, Z is an alkylene chain containing 2, 3 or 4 carbon atoms optionally substituted by one or more alkyl groups containing 1 to 3 carbon atoms. In more preferred compounds of formula I, Z is an alkylene chain containing 2, 3 or 4 carbon atoms optionally substituted by one or more methyl groups.
In preferred compounds of formula I, R is phenyl substituted by one or two chloro substituents, or R is naphthyl. In more preferred compounds of formula I, R is 3-chlorophenyl, 3,4-dichlorophenyl or 2-naphthyl.
In preferred compounds of formula I, R.sub.1 is an alkyl group containing 1 to 3 carbon atoms or is benzyl, and R.sub.2 is an alkyl group containing 1 to 3 carbon atoms. In more preferred compounds of formula I, R.sub.1 and R.sub.2 are both methyl or ethyl or R.sub.1 is benzyl and R.sub.2 is methyl. In especially preferred compounds of formula I, R.sub.1 and R.sub.2 are both methyl.
A preferred group of compounds of formula I is represented by formula III ##STR5## and pharmaceutically acceptable salts thereof in which m, n, X, Y, Z, R.sub.1 and R.sub.2 are as described above for formula I; R.sub.4 is H or halo (for example fluoro, chloro, bromo or iodo), or R.sub.3 and R.sub.4 together with the carbon atoms to which they are attached form a fused benzene ring.
In more preferred compounds of formula III, R.sub.3 is chloro and R.sub.4 is H, R.sub.3 and R.sub.4 are both chloro or R.sub.3 and R.sub.4 together with the carbon atoms to which they are attached form a fused benzene ring. In especially preferred compounds of formula III, R.sub.3 is chloro situated in the 3-substitution position on the phenyl ring and R.sub.4 is H, R.sub.3 and R.sub.4 are both chloro and are situated in the 3- and 4- substitution positions on the phenyl ring respectively, or R.sub.3 and R.sub.4 together with the phenyl ring to which they are attached form a 2-naphthyl group.
Compounds of formula I and III may exist as salts with pharmaceutically acceptable acids. Examples of such salts include hydrochlorides, hydrobromides, sulphates, methanesulphonates, nitrates, maleares, acetates, citrates, fumarates, tartrates [eg (+)-tartrates, (-)-tartrates or mixtures thereof including racemic mixtures], succinates, benzoates and salts with amino acids such as glutamic acid. Compounds of formula I and III and their salts may exist in the form of solyates (for example hydrates).
Certain compounds of formula I and III may exist in more than one crystal form and the present invention includes each crystal form and mixtures thereof.
It will be appreciated by those skilled in the art that compounds of formula I and III may contain one or more chiral centres. When compoun
REFERENCES:
patent: 5047432 (1991-09-01), Housley et al.
Harris Paul John
Heal David John
Knoll Aktiengesellschaft
Raymond Richard L.
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