Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-12-18
1999-02-16
Geist, Gary
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
5142335, 514456, 514617, 514906, 514825, 514886, 544151, 544106, 549398, 564180, A61K 31535
Patent
active
058721185
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/GB94/01003 filed May 10, 1994.
The present invention relates to amide compounds, synthesis thereof, intermediates, salts and solvates thereof, pharmaceutical compositions containing them and the use of such compounds and compositions in medicine and therapy, particularly as central muscle relaxants.
The major limiting side effects of many clinically effective central muscle relaxants and anticonvulsants are the induction of sedation and incoordination in the recipient, which severely limit their usefulness. Similar side effects are found with drugs used in the treatment of anxiety, such as benzodiazepines. Although these effects may be transient, patients on such therapy are often unable to drive or participate in certain occupations.
It has now surprisingly been found that amides of formula (I) are potent central muscle relaxants and have a significantly reduced liability to sedation and incoordination compared with known agents.
In one aspect the present invention provides the novel compounds of formula (I) ##STR2## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each selected from hydrogen and fluoro and at least one and not more than two is fluoro; and cyclo(C.sub.3 or C.sub.4)alkyl or together with the nitrogen form a morpholino group; and --O-- when any of R.sup.5, R.sup.6 and R.sup.7 is other than hydrogen and is always a bond when R.sup.5 and R.sup.6 together with the ring carbon form a carbonyl group;
As used herein, having 1, 2, 3 or 4 carbon atoms; carbon atoms; R.sup.9 is hydrogen; and formula (I) and a solvent therefor.
It will be appreciated that the compounds of formula (I) can exist in various geoisomeric forms and as mixtures thereof in any proportions. The present invention includes within its scope such geoisomeric forms or mixtures of geoisomers, including the individual E and Z isomers of the compounds of formula (I) as well as mixtures of such isomers, in any proportions.
Included within formula (I) are compounds wherein one or more carbon centers is/are chiral. The present invention includes within its scope each possible optical isomer substantially free from, i.e., associated with less than 5% of, any other optical isomer(s), as well as mixtures of one or more optical isomers in any proportions, including racemic mixtures thereof.
It will be evident to a skilled person that certain compounds of formula (I) can exist in enantiomeric forms according to the direction of rotation of plane polarized light when passed through a sample of the compound. Individual optical isomers as well as mixtures of such isomers in any proportions are within the scope of the invention.
As will be appreciated, structural formula (I) is merely a two-dimensional representation of the compounds.
Separate groups of compounds, within formula (I), include those wherein carbon atoms and more preferably methyl or ethyl; carbon atoms and more preferably methyl or ethyl; group; carbon atoms and more preferably methyl, ethyl or isopropyl; carbon atoms and more preferably methyl, ethyl or isopropyl; group;
Preferred as a class are compounds wherein the >C.dbd.O group and the benzene ring are on opposite sides of the exo double bond, and salts and solvates thereof.
Individual preferred compounds within formula (I) include de;
Particularly preferred is (E)-2-(4,6-difluoro-1-indanylidene)acetamide, together with its salts and solvates.
Preferred salts and solvates are those that are pharmaceutically acceptable.
The present invention further provides a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, for use in the medical treatment of a mammal including a human being.
The present invention also provides the use of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, for the manufacture of a medicament for the medical treatment of a mammal including a human being.
The pharmaceutically acceptable salts include ammonium salts; alkali metal salts, for example sodium and potassium salts; and alkaline earth metal salts, fo
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Cooper Barrett Randolph
Kelley James Leroy
McLean Ed Williams
Musso David Lee
Orr Gloria Faye
Carr Deborah D.
Geist Gary
Glaxo Wellcome Inc.
Makujina Shah R.
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