Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1983-07-28
1986-11-25
Hollrah, Glennon H.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
544377, 544389, A61K 31495, C07D29510
Patent
active
046249532
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INVENTION
The present invention is concerned with a novel series of diphenylbutyl-1-piperazinocarboxylates having valuable properties for treatment of mental disorders the preparation of such compounds, pharmaceutical compositions containing such compounds and the use of the compounds in human and veterinary medicine.
PRIOR ART
Japan Kokai 76 08,283 (CA 85: 33082m) describes as having analgetic properties piperazine derivatives of formula: ##STR2## wherein R.sup.1, R.sup.2 =H, alkyl, cycloalkyl, substituted Ph, NR.sup.1 R.sup.2 =heterocyclyl; R.sup.3 =H, halo, alkyl, alkoxy, CF.sub.3, OH; R.sup.4-6 =H, alkyl, substituted Ph, benzyl. Swedish patent application No. 7908701-1 describes as having psychotropic properties piperazine derivatives of formula: ##STR3## wherein R.sub.1 and R.sub.2 are groups independently selected from the group of hydrogen, alkyl straight or branched chains having from 1 to 10 carbon atoms, cycloalkyl having from 3 to 8 carbon atoms, aralkyl having from 7 to 9 carbon atoms, alkenyl having from 2 to 10 carbon atoms, phenyl unsubstituted or substituted by one to three substituents selected from halogen, including F, Cl and Br, lower alkyl having from 1 to 5 carbon atoms, lower alkoxy having from 1 to 5 carbons atoms, amine unsubstituted or substituted by one or two lower alkyl groups having from 1 to 5 carbon atoms, --CF.sub.3 and --CN groups, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are groups independently selected from hydrogen, lower alkyl having from 1 to 3 carbon atoms and phenyl, R.sub.7 is a group selected from hydrogen, halogen including F, Cl and Br, lower alkoxy having from 1 to 3 carbon atoms and --CF.sub.3 groups, and X is O or S.
Collect. Czech. Chem. Commun. 1980, 45 (11), 3182-89 mentions as an intermediate in a series of reactions the compound of formula: ##STR4## All the compounds A and B described in the above mentioned Japan Kokai No. 76 08,283 and Swedish patent application No. 7908701-1 are 1-piperazinecarboxamide derivatives and chemically not related to the compounds according to the present invention which are 1-piperazinecarboxylate derivatives.
Thus, the compounds A and B are chemically amides while the compounds according to the present invention are carboxylic esters.
Compound C is as the compounds according to the present invention a 1-piperazinecarboxylate derivative. However, said compound is only shown by means of a formula and not identified by any physical constant. Furthermore, there are no statements at all concerning any pharmacodynamic property of said compound.
DESCRIPTION OF THE INVENTION
It has now been found that compounds of formula I: ##STR5## wherein R is alkyl straight or branch chained having from 1 to 10 carbon atoms, cycloalkyl having from 3 to 8 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, R.sub.1 -R.sub.4 are independently H, CH.sub.3, C.sub.2 H.sub.5 with cis or trans configuration provided that only two of them are other than hydrogen, and pharmaceutically acceptable salts thereof unexpectedly exhibit valuable properties for treatment of mental disorders such as psychoses and aggression rendering them useful for treatment of humans and animals.
The compounds of formula (I) can generally be prepared
A(a) by reacting an appropriate chloroformate of formula (II) ##STR6## wherein R is as previously defined, with a 1-(4,4-diaryl-butyl)-piperazine of formula (III) ##STR7## wherein R.sub.1 -R.sub.4 are as previously defined, to form a compound of formula (I) or
A(b) by reacting a 1-piperazinocarboxylate of formula (IV) ##STR8## with a 4-substituted 1,1-diarylbutane of formula V ##STR9## wherein R and R.sub.1 -R.sub.4 are as above defined and Y is halogen, preferably Br or another reactive group, e.g. a mesyl or tosyl ester group, to form a compound of formula I.
The 1-piperazinocarbox
REFERENCES:
patent: 2819269 (1958-01-01), Weston et al.
patent: 4112091 (1978-09-01), Nesvadba et al.
patent: 4252804 (1981-02-01), Joullie et al.
Collection Czechoslov. Chem. Commun. 1980, 45 (11), 3182-89 published Mar. 10, 1980.
Arzneimittel-Forsch. Drug. Res., 27(1), No. 4, (1977) pp. 828-832, W. Meuldermans, et al., "In Vitro Metabolism of Lidoflazine by Rat and Dog Liver Fractions".
Chemical Abstracts, vol. 85 (1976), abstract No. 33082m, Japan Kokai 76 08, 283.
Bjoerk, et al., "Chemical Abstracts", vol. 99, 1983, col. 99:158462f.
Bjork Anders K.
Christensson Erik G.
Hollrah Glennon H.
Turnipseed James H.
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