Method and use

Details Method and use Method and use

2001-12-03

2003-06-03

Weddington, Kevin E. (Department: 1614)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C514S884000

Reexamination Certificate

active

06573291

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to the use of selected compounds to antagonize or inhibit GLP-1 activity in a mammal patient in need thereof, as well as to a pharmaceutical composition comprising such antagonist(s).
BACKGROUND OF THE INVENTION
Glucagon-like peptide 1(7-36)amide (GLP-1) is an intestinal hormone and neurotransmitter that is involved in the control of metabolism and food intake. A major function of the hormone appears to be the regulation of the amount of insulin released in response to a meal, GLP-1 increasing the insulin secretion. It has therefore been proposed that a molecule capable of augmenting the action of GLP-1, i.e. a GLP-1 agonist, should be useful as an antidiabetic agent to lower elevated blood glucose levels in a mammal serum.
Conversely, a GLP-1 antagonist could be used to elevate the blood glucose level in a subject afflicted with too low a blood glucose level. An exemplary such condition is postprandial reactive hypoglycemia, such as in partially gastrorectomised subjects (Toft-Nielsen M. et al., Diabetologia 41(10):1180-6, 1998). Other disorders where a GLP-1 antagonist is believed to be useful include anorexia (Jensen P. B. et al., J. Clin. Invest. 102(2):503-10, 1998), and reduced intestinal motility and constipation (Tolessa T. et al., Digestive diseases and Sciences 43(10):2284-99, 1998). It has also been suggested that a GLP-1 antagonist could be used to reduce symptoms in Alzheimer's disease, GLP-1 mediating the inhibition of beta-amyloid induced neural activation (Oka J. I. et al., SO Neuroreport 10(8):1643-6, 1999).
SUMMARY OF THE INVENTION
According to the present invention, a limited class of chemical compounds have been found which are excellent antagonists of GLP-1 and therefore would be useful for the treatment of diseases or disorders where inhibition of GLP-1 action would be indicated.
Therefore, in one aspect thereof, the present invention provides a method of antagonizing (e.g., inhibiting) GLP-1 activity in a mammalian patient, comprising administering to said patient an effective amount of a compound of the general formula I:
wherein:
R
1
and R
2
independently of each other are C
1-4
alkyl,
R
3
is halogen, hydroxy, C
1-4
-alkoxy or trifluoromethoxy, and
R
4
is hydrogen, hydroxy or C
1-4
-alkoxy,
or a pharmacologically acceptable salt thereof.
In another aspect, the present invention provides a compound of formula I above for use as a pharmaceutical.
In still another aspect, the present invention provides a pharmaceutical composition comprising a compound of formula I above and optionally a pharmaceutically acceptable carrier.
Yet another aspect of the present invention provides the use of a compound of formula I above for the preparation of a medicament for antagonizing GLP-1 activity in a mammalian patient.
This invention also features a method of treating a disorder where inhibition of GLP-1 activity is indicated. The method includes administering to a mammal subject in need thereof an effective amount of a compound of formula I above.
Further, this invention features a method of treating a disorder where inhibition of GLP-1 activity is indicated. The method includes administering to a mammal subject in need thereof a pharmaceutical composition, wherein the pharmaceutical composition includes an effective amount of a compound of formula I above and a pharmaceutically acceptable carrier.
Also within the scope of this invention is a method for the manufacture of a medicament for antagonizing GLP-1 activity in a mammalian patient, characterized in that a compound of formula I above is used as the pharmaceutically active substance.


REFERENCES:
patent: 6291476 (2001-09-01), Kordik et al.
patent: 0 142 190 (1985-05-01), None
patent: WO 93/03714 (1993-03-01), None
patent: WO 00/69849 (2000-11-01), None
STN International, File CAPLUS accession No. 1999:382989, Document No. 131:165408, Meurer, Janet A., et al. “Properties of native and in vitro glucosylated forms of the glucagon-like peptide-1 receptor antagonist exending(9-39)”, Metab., Clin. Exp. (1999), 48(6), pp. 716-724.

Affiliated with

Also associated with

Rating

Method 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 Method and use, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method and use will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3142407