Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1993-02-11
1995-07-11
Robinson, Douglas W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 51, 536 2854, A61K 3170, C07H 1909
Patent
active
054321662
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a new therapeutic use for a 5-substituted pyrimidine nucleoside.
1-(.beta.-D-arabinofuranosyl)-5-propynyluracil is already known as an anti-viral agent having activity against viruses of the herpes group, in particular Varicella Zoster virus and cytomegalovirus. In this connection reference can be made to EP-A-0 417 560.
The role of elevated serum cholesterol levels in many pathological conditions in man is now well established and deposits of cholesterol in the vascular system have been implicated as causative of a number of pathological conditions such as coronary heart disease. Cholesterol is found in the blood in the form of complex particles which generally consist of a core of cholesterol esters and triglyceride surrounded by phospholipid and protein. Cholesterol is carried to sites where it is deposited in blood vessels in the form of so-called low density lipoprotein (LDL) cholesterol and is removed from such sites in the form of so-called high density lipoprotein (HDL) cholesterol.
It has now surprisingly been found that 1(.beta.-D-arabinofuranosyl)-5-propynyluracil is effective in lowering serum cholesterol, and particularly LDL cholesterol, levels in cynomolgus monkeys and preliminary studies indicate a similar effect in human subjects.
Accordingly, the present invention provides a method for lowering serum cholesterol, particularly LDL cholesterol, levels in a human subject which comprises administering to the said subject an effective amount of 1-(.beta.-D-arabinofuranosyl)-5-propynyluracil or a pharmaceutically acceptable salt or physiologically labile ester thereof.
Examples of clinical conditions which may be treated in accordance with the present invention include polygenic hypercholesterolaemia, familial hypercholesterolaemia, LDL receptor deficiency/abnormality, apoB deficiency/abnormality, familial combined hyperlipidaemia, apoE2 homozygosity, apoC2 deficiency and familial lipoprotein lipase deficiency.
The present invention also provides the use of 1(.beta.-D-arabinofuranosyl) -5-propynyluracil or a pharmaceutically acceptable salt or physiologically labile ester thereof for the manufacture of a medicament for lowering serum cholesterol, particularly LDL cholesterol, levels in a human subject.
The present invention also provides a pharmaceutical composition for lowering serum cholesterol, particularly LDL cholesterol, levels in a human subject, which comprises 1(.beta.-D-arabinofuranosyl)-5-propynyluracil or a pharmaceutically acceptable salt or physiologically labile ester thereof, together with at least one pharmaceutically acceptable carrier or diluent.
1(.beta.-D-arabinofuranosyl)-5-propynyluracil, pharmaceutically acceptable salts and physiologically labile esters thereof, are known compounds and may be prepared by the methods described in EP-A-0 417,560. Suitable pharmaceutically acceptable salts for use according to the invention include salts formed with physiologically acceptable bases, for example alkali metal (e.g. sodium), alkaline earth metal (e.g. magnesium), ammonium and NX.sub.4.sup.+ (where X is for example C.sub.1-4 alkyl) salts. Pharmaceutically acceptable salts of 1(.beta.-D-arabinofuranosyl) -5-propynyluracil may be prepared in conventional manner, for example by reaction of 1(.beta.-D-arabinofuranosyl)-5-propynyluracil with the appropriate base.
As used herein, the term "physiologically labile ester" refers to an ester of 1-(.beta.-D-arabinofuranosyl)-5-propynyluracil which upon administration to a human subject is converted to 1(.beta.-D-arabinofuranosyl) -5-propynyluracil or a metabolite thereof having the same or similar cholesterol lowering activity to the parent compound. Examples of suitable mono- and di-esters include carboxylic acid esters in which the non-carbonyl moiety of the ester grouping is selected from straight or branched chain alkyl, alkoxyalkyl, carboxyalkyl, aralkyl, aryloxyalkyl and aryl (including aryl substituted by a substituent such as halogen, C.sub.1-4 alkyl or C.sub.1-4 alkoxy); sulphonate esters such as
REFERENCES:
patent: 4594339 (1986-06-01), Lopez et al.
patent: 4962194 (1990-10-01), Bridges
patent: 5028596 (1991-07-01), Purifoy et al.
patent: 5063233 (1991-11-01), Chen et al.
Eur. J. Med. Chem., Chim, Ther., (1980), 15 (1), 23-27.
Gaggi et al, Farmaco, Ed. Sci., (1980), 35 (7), 581-589.
de Clerq et al, J. Med. Chem. (1983), 26, 661-666.
Peck Richard W.
Posner John
Powell Kenneth
Brown Donald
Burroughs Wellcome Co.
Kunz Gary L.
Nielsen Lawrence A.
Robinson Douglas W.
LandOfFree
Use of 1-(.beta.-D-arabinofuranosyl) -5-propynyluracil for lower does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of 1-(.beta.-D-arabinofuranosyl) -5-propynyluracil for lower, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of 1-(.beta.-D-arabinofuranosyl) -5-propynyluracil for lower will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-503538