Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1994-04-14
1995-11-28
Ivy, C. Warren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514324, 514443, 514466, 549 51, 549466, 546202, 544146, A61K 31535, C07D33364, C07D30783
Patent
active
054708540
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/DE92/00435 filed May 25, 1992.
The invention relates to 2-phenylbenzo[b]furans and 2-phenylbenzo[b]thiophens, processes for their manufacture, and pharmaceutical preparations which contain them.
The new furans and thiophenes are characterised by general Formula I ##STR2## in which R.sup.1 and R.sup.2 independently of one another denote a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, a benzyl group, a group C(O)R.sup.4, where R.sup.4 is an alkyl or alkoxy group having 1 to 10 carbon atoms or a phenyl radical, or a carbamoyl group --C(O)NR.sup.5 R.sup.6, where R.sup.5 and R.sup.6 independently of one another are a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and n denotes an integer from 0 to 12 if R.sup.3 is a hydrogen atom, or n denotes an integer from 4 to 12 if R.sup.3 is an amino group --NR.sup.7 R.sup.8, where R.sup.7 and R.sup.8 independently of one another represent a hydrogen atom or an alkyl group having 1 to 10 carbon atoms or R.sup.7 and R.sup.8 together represent an alkylene group --(CH.sub.2).sub.m -- or the group --(CH.sub.2) .sub.2 O(CH.sub.2).sub.2 -- or R.sup.3 denotes an amide group --C(O)NR.sup.7 R.sup.8, where R.sup.7 and R.sup.8 have the abovementioned meanings, or R.sup.3 denotes a sulphinyl group --S(O)R.sup.9, where R.sup.9 is the radical --(CH.sub.2).sub.m (CF.sub.2).sub.o CF.sub.3 and m and o are 2, 3, 4, 5 or 6 and x denotes an oxygen or sulphur atom.
Radicals of organic carbon acids, which may be saturated or unsaturated, may be considered as alkanoyl groups --C(O)R.sup.4. They are derived from aliphatic, cycloaliphatic, aliphatic-cycloaliphatic, cycloaliphatic-aliphatic and aromatic monocarbon acids. The number of carbon atoms in the ring varies from 3 to 7. The alkanoyloxy groups of acetic, propanoic, butyric, isobutyric, pivalic, caproic, acrylic, crotonic, heptylic, caprylic, pelargonic, decanoic, 3-cyclopentylpropanoic and benzoic acids are preferred as radicals R.sup.1 and R.sup.2.
Radical R.sup.1 may be found in positions 4,5,6 and 7 of the bi-cycle, but positions 5 and 6 are particularly well-suited.
Alkyl groups having between 1 and 10 carbon atoms and cycloalkyl groups having between 3 and 7 carbon atoms may be considered as radicals R.sup.5 and R.sup.6.
Methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl and decanyl radicals are suitable for alkyl groups R.sup.5,R.sup.6, R.sup.7 and/or R.sup.8. Cyclopentyl and cyclohexyl radicals are mentioned in particular as cycloalkyl groups.
The benzyl group is mentioned in particular as an example of an aralkyl group for radicals R.sup.4, R.sup.5 and/or R.sup.6.
Radicals R.sup.7 and R.sup.8 may be the same or different or parts of a common ring. If a ring is present, it may contain an oxygen atom in addition to the nitrogen atom. Particularly suitable for these radicals are the following combinations: hydrogen/methyl (derived from methylamine), hydrogen/hydrogen (derived from amine), methyl/methyl (derived from dimethylamine), and the --(CH.sub.2).sub.4 -- radical (derived from pyroiidine), the --(CH.sub.2).sub.5 --radical (derived from piperidine), and the --(CH.sub.2).sub.2 --O--(CH.sub.2).sub.2 radical (derived from morpholine).
The invention relates in particular to the following compounds:
The invention also relates to a process for manufacturing the 2-phenylbenzo-[b]furans and -thiophens of general Formula I.
According to this process ##STR3## in which R.sup.1' and R.sup.2' independently of one another each denote an alkyl group having 1 to 4 carbon atoms and where Hal is a halogen atom and in particular a bromine atom, a vinyl radical --CH.dbd.CH.sub.2 or a radical --CH.sub.2 --C(O)NR.sup.7 R.sup.8 is cyclised with a Lewis acid with cleavage of the ether groups to give a compound of the general formula Ia ##STR4## and if R.sup.3' denotes --(CH.sub.2).sub.2 --Hal, Hal is exchanged by reaction of the compound of the formula Ia with a primary, secondary or cyclic amine of the formula HNR.sup.7 R.sup.8 for the corresponding amine radical --NR.sup.7 R.su
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Erber Sebastian
Schneider Martin
von Angerer Erwin
Ivy C. Warren
Owens Amelia
Schering Aktiengesellschaft
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