N-substituted azabicycloheptane derivatives, their preparation a

Details N-substituted azabicycloheptane derivatives, their preparation a N-substituted azabicycloheptane derivatives, their preparation a

1996-04-19

1997-04-01

Richter, Johann

Organic compounds -- part of the class 532-570 series

Organic compounds

Chalcogen in the nitrogen containing substituent

544230, 544318, 544349, 546183, 546221, 548208, 548230, 5483625, 548411, 548434, 548454, C07D20952

Patent

active

056167059

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/EP94/03910 Nov. 26, 1994.
The invention relates to novel N-substituted azabicycloheptane derivatives, their preparation and use for preparing pharmaceuticals.
It has been disclosed that basically substituted butyrophenone derivatives or benzamide derivatives have neuroleptic or cerebro-protective activity (U.S. Pat. No. 4,605,655, EP 410 114, DE 12 89 845, EP 400 661, DE 29 41 880, EP 190 472, DE 42 19 973).
The observed high affinities to dopamine and serotonin receptor subtypes appear to play a particular role in this context. It has now been found that N-substituted 3-azabicyclo[3.2.0]-heptane derivatives of the formula I ##STR2## where R.sup.1 is a phenyl or thienyl group which is unsubstituted or mono- or disubstituted by halogen atoms or C.sub.1 -C.sub.4 -alkyl, trifluoromethyl, hydroxyl, C.sub.1 -C.sub.4 -alkoxy, amino, monomethylamino, dimethylamino, cyano or nitro groups, substituted by halogen, methoxy, hydroxyl or amino, ##STR3## R.sup.3 is a hydrogen atom or a hydroxyl radical, R.sup.4 is a hydrogen atom or substituted by fluorine or chlorine, hydroxyl or methoxy or monosubstituted by amino, C.sub.1-4 -alkylamino or di-C.sub.1-4 -alkylamino or a thienyl, naphthyl, benzofuryl, benzothienyl, indolyl, N-methylindolyl or indenyl group which is unsubstituted or substituted by fluorine, chlorine or nitro or a C.sub.3 - to C.sub.6 -cycloalkyl group, amino, spirocyclopropane ring, substituted by fluorine or chlorine, or a cyano group, pharmacological properties.
In the formula I, the substituents R.sup.1 to R.sup.10 and n preferably have the following meanings: chlorine, iodine, methoxy, trifluoromethyl or nitro,
The compounds of the formula I according to the invention can be prepared by reacting a compound of the formula II group, with a 3-azabicyclo[3.2.0]heptane derivative of the formula III ##STR4## where R.sup.1 is a phenyl or thienyl group which is unsubstituted, mono- or disubstituted by halogen atoms or C.sub.4 -C.sub.4 -alkyl, trifluoromethyl, hydroxyl, C.sub.1 -C.sub.4 -alkoxy, amino, monomethylamino, dimethylamino, cyano or nitro groups and substituted by halogen, methoxy, hydroxyl or amino, addition salts with physiologically tolerable acids.
Suitable nucleofugic leaving groups for Nu are preferably halogen atoms, in particular bromine or chlorine.
The reaction is expediently carried out in the presence of an inert base, such as triethylamine or potassium carbonate, as acid acceptor in an inert solvent, such as a cyclic saturated ether, in particular tetrahydrofuran or dioxane, or a benzene hydrocarbon, such as toluene or xylene.
The reaction is in general carried out at from 20.degree. to 150.degree. C., and is in general complete within from 1 to 10 hours.
The compounds of the formula I according to the invention can either be recrystallized by recrystallization from the customary organic solvents, preferably from a lower alcohol, such as ethanol, or purified by column chromatography.
Racemates can be resolved into the enantiomers in a simple manner by classical cleavage using optically active carboxylic acids, eg. tartaric acid derivatives, in an inert solvent, eg. lower alcohols.
The free 3-azabicyclo[3.2.0]heptane derivatives of the formula I can be converted to the acid addition salt of a pharmacologically tolerable acid in a customary manner, preferably by treating a solution with an equivalent of the corresponding acid. Pharmaceutically tolerable acids are, for example, hydrochloric acid, phosphoric acid, sulfuric acid, methanesulfonic acid, sulfamic acid, maleic acid, fumaric acid, oxalic acid, tartaric acid or citric acid.
The compounds according to the invention have useful pharmacological properties. They can be used as neuroleptics (in particular atypical), antidepressants, sedatives, hypnotics, CNS protectants or muscle relaxants. Several of the active qualities can occur in combination in one compound according to the invention. Demonstration of the pharmacological action is carried out both in vivo and in vitro, substance characterization in

Affiliated with

Also associated with

Rating

N-substituted azabicycloheptane derivatives, their preparation a does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with N-substituted azabicycloheptane derivatives, their preparation a, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and N-substituted azabicycloheptane derivatives, their preparation a will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-540051