Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-03-31
1996-02-27
Ramsuer, Robert W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514253, 514318, 514337, 544131, 544364, 546193, 546269, A61K 3144, A61K 31535, C07D40714, C07D41314
Patent
active
054949106
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP93/02833 filed Oct. 14, 1993.
This invention relates to benzofuran derivatives, to processes for their preparation, to pharmaceutical compositions containing them and to their medical use, in particular to compounds and compositions of use in the treatment of migraine.
The invention thus provides compounds of formula (I) ##STR2## wherein R.sup.1 is --CH.sub.2 CONR.sup.3 R.sup.4 ; form a saturated 4- to 7-membered ring formula ##STR3## where Z is a group of formula --CR.sup.7 R.sup.8 --, --O-- or --NR.sup.9 --; C.sub.1-3 alkyl; hydroxy or C.sub.1-3 alkoxy;
As used herein, an alkyl group may be a straight chain alkyl group, for example a methyl or ethyl group, or a branched chain alkyl group, for example an isopropyl group.
In a preferred class of compounds of formula (I) R.sup.3 and R.sup.4, together with the N-atom to which they are attached, form an azetidine, pyrrolidine, piperidine, hexamethyleneimine, piperazine or morpholine ring.
Typical values of R.sup.1 include ##STR4##
A particularly preferred class of compounds of formula (I) includes compounds wherein R.sup.5 and R.sup.6 are both methyl.
Preferred compounds according to the invention include: dine; idine; line; eridinol; hoxypiperidine; ylsulphonyl)piperazine; dine; morpholine;
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. 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.
Compounds of the invention may be isolated in association with solvent molecules by crystallisation from or evaporation of an appropriate solvent. Such solvates are included within the scope of the present invention.
References hereinafter to a compound according to the invention include both the compounds of formula (I) and their pharmaceutically acceptable salts and solvates.
The compounds of formula (I) are selective agonists at 5HT.sub.1 -like receptors and have selective vasoconstrictor activity. The selective 5HT.sub.1 -like receptor agonist activity and selective vasoconstrictor activity of the compounds of the invention has been demonstrated in vitro. In addition, compounds of the invention selectively constrict the carotid arterial bed of the anaesthetised dog whilst having negligible effect on blood pressure.
The compounds of the invention are indicated in the treatment of conditions susceptible to amelioration by agonist activity at 5HT.sub.1 -like receptors. In particular, compounds of the invention are useful in treating certain conditions associated with cephalic pain. In particular the compounds are useful in the treatment of migraine (including paediatric migraine), cluster headache, chronic paroxysmal hemicrania, headache associated with vascular disorders, tension-type headache, headache associated with substances of their withdrawal (e.g. drug withdrawal), trigeminal neuralgia, and headache associated with meningeal irritation, and in alleviating the symptoms associated therewith.
There is thus provided in a further aspect of the invention a compound of the invention or a salt thereof for use in therapy, in particular in human medicine. It will be appreciated that use in therapy embraces but is not necessarily limited to use of a compound of the invention or a salt thereof as an active therapeutic substance.
There is also provided as a further aspect of the invention the use of a compound of the invention in the preparation of a medicament for use in the treatment of conditions associated with cephalic pain, in particular migraine, cluster headache, chronic paro
North Peter C.
Wadman Sjoerd N.
Glaxo Group Limited
Ramsuer Robert W.
LandOfFree
Benzofuran derivatives as 5-HT.sub.1 -like receptor antagonists does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Benzofuran derivatives as 5-HT.sub.1 -like receptor antagonists, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Benzofuran derivatives as 5-HT.sub.1 -like receptor antagonists will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1679417