Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-06-05
1996-10-29
Bond, Robert T.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
540517, C07D24314, A61K 3155
Patent
active
055696546
DESCRIPTION:
BRIEF SUMMARY
This invention relates to novel amine derivatives, to processes for their preparation, to pharmaceutical compositions containing them and to their use in medicine.
In particular the invention relates to 5-aminoalkyl-1,4-benzodiazepine derivatives which modulate the effects of gastrin and/or cholecystokinin (CCK) in mammals.
Thus the invention provides compounds of general formula (I) ##STR2## and physiologically acceptable salts thereof; wherein R.sub.1 represents CH.sub.2 CONR.sub.5 R.sub.6 or CH.sub.2 COR.sub.7 ; R.sub.2 represents a phenyl group optionally substituted by 1 or 2 substituents selected from halogen, alkyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, amino, substituted amino, hydroxy, alkoxy, methylenedioxy, alkoxycarbonyl, oxazolyl or oxadiazolyl; R.sub.3 and R.sub.4 together with the nitrogen atom to which they are attached form a saturated 5-7 membered heterocyclic ring, which ring may contain an additional heteroatom selected from oxygen, sulphur or nitrogen; halogen, or R.sub.5 and R.sub.6 together with the nitrogen atom to which they are attached represent a saturated 5 to 7 membered heterocyclic ring which may be optionally substituted by 1 or 2 methyl groups or fused to a benzene ring; substituted phenyl;
It will be appreciated that compounds of formula (I) possess at least one asymmetric carbon atom (namely the carbon atom occupying the 3-position of the diazepine ring) and the compounds of the invention thus include all stereoisomers and mixtures thereof including the racemates.
In the compounds of formula (I) the term alkyl as a group or part of a group refers to a straight or branched chain alkyl group containing 1 to 4 carbon atoms and includes methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or tert-butyl.
Halogen in the definition of compounds of formula (I) may represent a fluoro, chloro, bromo or iodo substituent.
When R.sub.7 represents C.sub.1-4 alkyl examples of suitable groups include t-butyl.
When R.sub.7 represents optionally substituted phenyl examples of suitable groups includes phenyl or phenyl substituted by a methyl group e.g. 2-methylphenyl.
When NR.sub.5 R.sub.6 represents a saturated 5- to 7-membered heterocyclic ring this may be for example pyrrolidino, piperidino or hexamethylenimino which rings may be substituted by one or two methyl groups, such as 2,5-dimethyl pyrrolidino, 3,3 dimethylpyrrolidino, 3,3 dimethylpiperidino or 4,4-dimethylpiperidino.
When NR.sub.5 R.sub.6 represents a saturated heterocyclic ring fused to a benzene ring this may be for example a group selected from ##STR3##
When NR.sub.3 R.sub.4 represents a 5-7 membered saturated heterocyclic ring this may be for example pyrrolidino, piperidino, hexamethylenimino, morpholino, thiomorpholino and oxides thereof, piperazino or an N-substitued derivative thereof e.g. N-methyl piperazino or N-alkoxycarbonyl piperazino.
When R.sub.3 and R.sub.4 represent C.sub.1-4 alkyl examples of suitable groups include methyl, ethyl, ispropyl, propyl or n-butyl.
The alkylene chain A in the compounds of formula (I) is preferably a straight chain alkylene such as methylene, ethylene, propylene or butylene.
When R.sub.8 represents halogen examples of suitable groups include chlorine or fluorine.
The term oxazolyl refers to a 1,3 oxazolyl group which is linked to the rest of the molecule via the carbon atom in the 2 or 5 position.
The term oxadiazolyl refers to a 1,2,4 oxadiazolyl group which is linked to the rest of the molecule via the carbon atom in the 3 or 5 position.
In compounds of formula (I) the term substituted amino means C.sub.1-4 alkylamino, e.g. isopropylamino, diC.sub.1-4 alkylamino e.g. dimethylamino, C.sub.1-4 alkanoylamino or C.sub.1-4 alkoxycarbonylamino e.g. t-butoxycarbonylamino.
When R.sub.2 is phenyl containing a single substituent this is preferably in the meta or para position.
A preferred class of compounds of formula (I) include those wherein R.sub.1 represents the group CH.sub.2 CONR.sub.5 R.sub.6. Within this class particularly prefer
Armour Duncan R.
Box Philip C.
Shah Pritom
Bond Robert T.
Glaxo Group Limited
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