Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-06-14
1997-05-27
Powers, Fiona T.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
548430, A61K 3140, C07D491048
Patent
active
056332769
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP 94/04,220 filed Dec. 20, 1994, published as WO95/17405, Jun. 29, 1995.
This invention relates to tricyclic indoline derivatives, to processes for their preparation, to pharmaceutical compositions containing them and to their medical use.
The invention thus provides compounds of formula (I) ##STR2## wherein R.sup.1 is hydrogen, halogen or C.sub.1-6 alkyl; COR.sup.6 ; hydrogen or C.sub.1-6 alkyl;
It will be appreciated that in formula (I) hereinabove the substituent R.sup.1 may be attached at either available position on the phenyl portion of the tricylic ring.
As used herein, an alkyl group may be a straight chain or branched chain alkyl group. Examples of suitable alkyl groups include C.sub.1-4 alkyl groups, for example methyl, ethyl and isopropyl groups. A preferred alkyl group is methyl.
A halogen substituent may be, for example, fluorine, chlorine, bromine or iodine.
R.sup.2 preferably represents a group --CR.sup.3 R.sup.4 (CH.sub.2).sub.p NHCOR.sup.6 wherein R.sup.3 and R.sup.4 each independently represent hydrogen or C.sub.1-3 alkyl (e.g. methyl), p is an integer of 1 or 2, especially 1, and R.sup.6 is C.sub.1-3 alkyl (e.g. methyl) or C.sub.3-5 cycloalkyl (e.g. cyclopropyl or cyclobutyl).
Examples of the group R.sup.1 include hydrogen, halogen (e.g. chlorine) and C.sub.1-3 alkyl (e.g. methyl).
A preferred group of compounds of the invention are compounds of formula (Ia) ##STR3## and pharmaceutically acceptable salts and solvates (e.g. hydrates) thereof, wherein R.sup.1 and R.sup.2 are as defined hereinabove.
It is to be understood that the present invention covers all combinations of particular and preferred groups described hereinabove.
Particular compounds according to the present invention include: e; [2-(2,3,7,8-tetrahydro-1H-furo[2,3-g]indol-1-yl)-ethyl]-amide;
A particularly suitable compound according to the present invention is N-[2-(2,3,7,8-Tetrahydro-1H-furo[2,3-g]indol-1-yl)-ethyl]-acetamide, and pharmaceutically acceptable salts and solvates thereof.
Pharmaceutically acceptable salts of the compounds of formula (I) include those derived from pharmaceutically acceptable inorganic and organic acids. Examples of suitable acids include hydrochloric, hydrobromic, sulphuric, nitric, perchloric, fumaric, maleic, phosphoric, glycollic, lactic, salicylic, succinic, toluene-p-sulphonic, tartaric, acetic, citric, methanesulphonic, formic, benzoic, malonic, naphthalene-2-sulphonic and benzenesulphonic acids. A particularly suitable pharmaceutically acceptable salt of the compounds of formula (I) is the hydrochloride salt. Other acids such as oxalic, while not, in themselves pharmaceutically acceptable, may be useful as intermediates in obtaining the compounds of the invention and their pharmaceutically acceptable acid addition salts.
References hereinafter to a compound of formula (I) includes the compound and its pharmaceutically acceptable salts.
The compounds of formula (I) may contain at least one asymmetric carbon atom and may exist as stereoisomers. The compounds of formula (I) thus include the d- and l-isomers and mixtures, for example racemic mixtures, thereof.
The compounds of formula (I) are of use in the treatment of disorders which arise from a disturbed functioning of the melatonin system. In particular the compounds of formula (I) may be used in the treatment of chronobiological disorders, especially in the elderly population, glaucoma, cancer, psychiatric disorders, osteoporosis, neurodegenerative diseases or neuroendocrine disorders arising as a result of or influenced by the melatonin system.
Chronobiological disorders include seasonal affective disorders (SAD), primary and secondary insomnia disorders, primary and secondary hypersomnia disorders, sleep-wake schedule disorders (including advanced phase type, delayed phase type, disorganised type and frequently-changing type) and other dyssomnias, especially those caused by ageing, dementias, blindness shift work and by rapid time-zone travel, commonly known as jet lag.
Cancers which may be treated w
REFERENCES:
patent: 4680411 (1987-07-01), Picart
patent: 4738972 (1988-04-01), Eggler et al.
Kim et al., Canadian Journal of Chemistry, vol. 60, No. 16, 1982, 2093-2098 .
Carter Malcolm C.
North Peter C.
Glaxo Group Limited
Powers Fiona T.
LandOfFree
Indoline derivatives, method of preparation and use does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Indoline derivatives, method of preparation and use, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Indoline derivatives, method of preparation and use will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2329402