Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-05-04
1998-01-13
Jordan, Kimberly
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514824, A61K 3140
Patent
active
057080194
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/US94/04683, filed Apr. 28, 1994, published as WO94/25024 Nov. 10, 1994.
This invention also relates to pharmaceutical compositions containing an azaspirane derivative.
BACKGROUND OF THE INVENTION
Badger et al., J. Med. Chem., 33, 2963-2970, (1990) describes the structure activity relationships of azaspirane derivatives in antiarthritic and suppressor cell inducing assays. The cited reference disclosed compounds found to be active and inactive in the assays utilized therein. Badger, et al. concluded that one such compound, dihydrochloride, exhibited no biologically significant activity.
SUMMARY OF THE INVENTION
This invention relates to a a method of treatment of hyperlipidemia in a mammal, including a human, in need thereof which comprises administering to such mammal an effective amount of a compound of the Formula I ##STR1## wherein:
n is 1 or 2;
R.sup.1 and R.sup.2 are the same or different and are selected from hydrogen or straight chain, branched chain or cyclic alkyl, provided that the total number of carbon atoms contained in R.sub.1 and R.sub.2 when taken together is 0-10; or R.sup.1 and R.sup.2 are joined together to from a cyclic alkyl group having 3-7 carbon atoms; and
R.sup.3 and R.sup.4 are the same or different and are selected from hydrogen or methyl; or a pharmaceutically acceptable salt, hydrate or solvate thereof.
This invention also relates to pharmacetuical compositions containing compounds of Formula I.
DETAILED DESCRIPTION OF THE INVENTION
The term "hyperlipidemia" as used in the specification and in the claims is meant the presence of an abnormally high level of lipids in the blood.
The term "antihyperlipidemic" as used herein is meant the lowering of excessive lipid concentrations to desired levels.
Preferred lipids, of which high levels thereof are treated by the presently invented methods, are; cholesterol, triglycerides and low-density lipoproteins.
Compounds of Formula (I) can be prepared by known methods such as described in Badger, et al. J. Med. Chem., 33, 2963-2970, (1990) and in U.S. Pat. No. 4,963,557.Pharmaceutically acceptable salts, hydrates and solvates of the compound of structure (I) are formed, when appropriate, by methods well known to those of skill in the art.
Compounds of the present invention which are useful in the treatment of hyperlipidemia and which are included in the pharmaceutical compositions of the invention are those having Formula I ##STR2## wherein:
n is 1 or 2;
R.sup.1 and R.sup.2 are the same or different and are selected from hydrogen or straight chain, branched chain or cyclic alkyl, provided that the total number of carbon atoms contained in R.sub.1 and R.sub.2 when taken together is 0-10; or R.sup.1 and R.sup.2 are joined together to from a cyclic alkyl group having 3-7 carbon atoms; and
R.sup.3 and R.sup.4 are the same or different and are selected from hydrogen or methyl; or a pharmaceutically acceptable salt, hydrate or solvate thereof.
Preferred among the compounds of Formula I is
As used herein, the term compound of the structure ##STR3## Preferably when the compound as described herein said compound will be in the form of a dihydrochloride salt.
It has now been discovered that compounds of Formula I and pharmaceutically acceptable salts, hydrates and solvates thereof are useful for treatment of hyperlipidemia in a mammal, including humans, in need of such treatment. dihydrochloride (hereinafter compound A) was tested for its in vivo potency in lowering serum cholesterol in normal cholesterolemic dogs in two experiments.
To perform experiment I a total of 3 female pure bred normal cholesterolemic beagle dogs (Marshall Animal Farms, Inc., North Rose, N.Y.) were used. The dogs weighed between 8 and 15 kilograms at the start of the study. The dogs were maintained on tap water, which was available ad libitum from an automatic watering system, and standard laboratory chow (Pruina Laboratory Cainine Chow.RTM.). The 3 dogs were set up in 3 units and dosed once a day with 1.0 mg/kg of compound A. The chol
REFERENCES:
patent: 4291030 (1981-09-01), Mulinos
patent: 4963557 (1990-10-01), Badger et al.
Chemical Abstracts, vol. 119, Apr. 1993, Bugelski, et al., abstract No. 80231.
J. Med. Chem. 1990, 33, pp. 2963-2970.
Jordan Kimberly
SmithKline Beecham Corporation
LandOfFree
Methods of treating hyperlipidemia using azaspirane derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods of treating hyperlipidemia using azaspirane derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods of treating hyperlipidemia using azaspirane derivatives will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-326711