Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Patent
1982-01-25
1985-01-08
Hollrah, Glennon H.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
544377, 544386, 544379, 544391, A61K 31495, C07D24104
Patent
active
044926987
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INVENTION
The present invention relates to novel diphenylbutyl-1-acylpiperazines and their acid addition salts having pharmacologically valuable properties, processes for the preparation thereof and therapeutic compositions containing said compounds.
PRIOR ART
French Pat. No. 2,367,067 (CA 89: 24362 h) describes as having analgetic properties piperazine derivatives of formula: ##STR2## wherein R represents a lower unsaturated alkyl or furyl group or a lower alkyl group optional substituted by a lower alkoxy group, R.sub.1 and R.sub.2 represent a methyl or ethyl group, R.sub.3 represents a hydrogen atom or a methyl or a methoxy or a hydroxy group, X is O, CO, CO.sub.2, CR.sub.4 R.sub.5 or NCOR.sub.6, R.sub.4 represents a hydrogen atom or a lower alkoxy or a lower acyloxy or a hydroxy group, R.sub.5 represents a hydrogen atom or a phenyl group, R.sub.6 represents a lower alkyl group and n is 1, 2 or 3.
In the article "In vitro Metabolism of Lidoflazine by Rat and Dog Liver Fractions" by W. Meuldermans et al in Arzneim.-Forsch./Drug Res. 27 (I) 832 (1977) the compound 1-acetyl-4-[4,4-(di-fluorophenyl)butyl]piperazine is incidentally shown as a Lidoflazine metabolite among a number of other metabolites in a scheme illustrating metabolic pathways of lidoflazine. However, said compound is only shown by means a formula and there are no statements at all concerning any properties of the compound.
DESCRIPTION OF THE INVENTION
It has now been found that compounds of formula I: ##STR3## wherein R' is alkyl straight or branch chained having from 2 to 10 carbon atoms, preferably 2-3 carbon atoms, cycloalkyl having from 3 to 8 carbon atoms, preferably 3 carbon atoms, aralkyl having from 7 to 9 carbon atoms or phenyl unsubstituted or substituted by one to three F, Cl, Br, lower alkyl having from 1 to 5 carbon atoms, lower alkoxy having from 1 to 5 carbon atoms, alkylenedioxy having from 1 to 3 carbon atoms, --CF.sub.3 or --CN substituents and their pharmaceutically acceptable salts unexpectedly exhibit valuable anti-aggressive, antipsychotic and antidepressive properties. Furthermore, the compounds of formula I exhibit very potent analgetic properties.
Among the compounds A described in the above mentioned French patent specification No. 2,367,067, which have been found to possess analgetic properties, the compound which is most closely related to the compounds according to the present invention is the compound wherein R=ethyl, R.sub.1 =R.sub.2 =methyl, X=CH-Ph, R.sub.3 =H, n=2, which hereinafter is referred to as compound A.sub.1. However, said compound A.sub.1 differs chemically in several respects from the compounds according to the present invention. Thus, the known compound A.sub.1 have no fluorine substituents in the two benzene rings and furthermore, the known compound has methyl substituents in positions 2 and 5 of the piperazine ring which is not the case for the compounds according to the present invention. Fluorine substitution in the para position of the benzene rings and hydrogen substitution in positions 2 and 5 of the piperazine ring of the known compound A.sub.1 carried out separately or in combination in all cases substantially reduce the potency relative to compound A.sub.1. However, it has according to the present invention surprisingly been found that lengthening of the side-chain together with fluorine substitution in the para position of the benzene rings and the absence of any C-substitution in the piperazine ring, i.e. the compound of Formula I according to the present invention wherein R'=ethyl, leads to a tenfold increase in potency and prolonged activity relative to compound A.sub.1. This demonstrates the important and unexpected improvements obtained by means of the compounds I according to the present invention as compared to the most closely related prior art.
As already is pointed out above the cited article of Meuldermans et al only by means of a formula shows the compound 1-acetyl-4-[4,4-(di-fluorophenyl)butyl]piperazine, hereinafter referred to as compound B, as a metabol
REFERENCES:
patent: 2742472 (1956-04-01), Baltzly et al.
patent: 2794804 (1957-06-01), Kushner et al.
patent: 4080453 (1978-03-01), Nishimura et al.
patent: 4265894 (1981-05-01), Gootjes
patent: 4308387 (1981-12-01), Bjork
Bjork, et al., "Chemical Abstracts", vol. 99, 1983, Col. 99:158462f.
Abramo Aina L.
Bjork Anders K.
Christensson Erik G.
Hollrah Glennon H.
Turnipseed James H.
LandOfFree
Diphenylbutyl-1-acylpiperazines does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Diphenylbutyl-1-acylpiperazines, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Diphenylbutyl-1-acylpiperazines will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-113195