Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-11-04
1999-11-02
Davis, Zinna Northington
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514352, 544332, 546312, 548110, 548252, 548253, 556416, C07D21373, C07D23942, A61K 3144
Patent
active
059771240
DESCRIPTION:
BRIEF SUMMARY
This is a National Phase filing under 35 U.S.C. .sctn.371 based on PCT/IB95/00344 which was filed internationally on May 10, 1995.
BACKGROUND OF THE INVENTION
The present invention relates to certain compounds of the formula (I) depicted below, which are .beta.-adrenergic receptor agonists and accordingly have utility as, inter alia, hypoglycemic and antiobesity agents. The invention also relates to methods for the compounds use and to pharmaceutical compositions containing them. The compounds of the present invention also possess utility for increasing lean meat deposition and/or improving the lean meat to fat ratio in edible animals, i.e. ungulate animals and poultry.
The compounds of this invention further possess utility in the treatment of intestinal motility disorders, depression, prostate disease, dyslipidemia, and airway inflamatory disorders such as asthma and obstructive lung disease.
The disease diabetes mellitus is characterized by metabolic defects in production and utilization of carbohydrates which result in the failure to maintain appropriate blood sugar levels. The result of these defects is elevated blood glucose or hyperglycemia. Research in the treatment of diabetes has centered on attempts to normalize fasting and postprandial blood glucose levels. Current treatments include administration of exogenous insulin, oral administration of drugs and dietary therapies.
Two major forms of diabetes mellitus are recognized. Type I diabetes, or insulin-dependent diabetes, is the result of an absolute deficiency of insulin, the hormone which regulates carbohydrate utilization. Type II diabetes, or non-insulin dependent diabetes, often occurs with normal, or even elevated levels of insulin and appears to be the result of the inability of tissues to respond appropriately to insulin. Most of the Type II diabetics are also obese.
The compounds of the present invention and the pharmaceutically active salts thereof effectively lower blood glucose levels when administered orally to mammals with hyperglycemia or diabetes.
The compounds of the present invention also reduce body weight or decrease weight gain when administered to mammals. The ability of these compounds to affect weight gain is due to activation of .beta.-adrenergic receptors which stimulate the metabolism of adipose tissue.
.beta.-Adrenergic receptors have been categorized into .beta..sub.1, .beta..sub.2 and .beta..sub.3 -subtypes. Agonists of .beta.-receptors promote the activation of adenyl cyclase. Activation of .beta..sub.1 -receptor receptors invokes increases in heart rate while activation of .beta..sub.2 -receptors induces relaxation of skeletal muscle tissue which produces a drop in blood pressure and the onset of smooth muscle tremors. Activation of .beta..sub.3 -receptors is known to stimulate lipolysis (the breakdown of adipose tissue triglycerides to glycerol and free fatty acids) and metabolic rate (energy expenditure), and thereby promote the loss of fat mass. Compounds that stimulate .beta.-receptors are therefore useful as anti-obesity agents, and can also be used to increase the content of lean meat in edible animals. In addition, compounds which are .beta..sub.3 -receptor agonists have hypoglycemic or anti-diabetic activity, but the mechanism of this effect is unknown.
Until recently .beta..sub.3 -adrenergic receptors were thought to be found predominantly in adipose tissue. .beta..sub.3 -receptors are now known to be located in such diverse tissues as the intestine (J. Clin. Invest., 91, 344 (1993)) and the brain (Eur. J. Pharm., 219,193 (1992)). Stimulation of the .beta..sub.3 -receptor has been demonstrated to cause relaxation of smooth muscle in colon, trachea and bronchi. Life Sciences, 44(19), 1411 (1989); Br. J. Pharm., 112, 55 (1994); Br. J. Pharmacol., 110, 1311 (1993). For example, stimulation of .beta..sub.3 -receptors has been found to induce relaxation of histamine-contracted guinea pig ileum, J.Pharm.Exp.Ther., 260, 1, 192 (1992).
The .beta..sub.3 -receptor is also expressed in human prostate. Because stim
REFERENCES:
patent: 4358455 (1982-11-01), Atkinson et al.
patent: 4800206 (1989-01-01), Alig et al.
patent: 4988714 (1991-01-01), Alig et al.
patent: 5019578 (1991-05-01), Fisher et al.
patent: 5216170 (1993-06-01), Lindel et al.
patent: 5599966 (1997-02-01), Bron et al.
A. R. Peters; Veterninary Record; 124; 417-420 (1989).
English Translation of JP 8-165276, 1996.
English language Abstracts (2) of Japanese 8165276 plus page of formulae.
Benson Gregg C.
Davis Zinna Northington
Jones James T.
Pfizer Inc.
Richardson Peter C.
LandOfFree
.beta.-adrenergic agonists does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with .beta.-adrenergic agonists, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and .beta.-adrenergic agonists will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2135806