Bivalent ligands effective for blocking ACAT enzyme for lowering

Details Bivalent ligands effective for blocking ACAT enzyme for lowering Bivalent ligands effective for blocking ACAT enzyme for lowering

1992-09-29

1994-04-19

Daus, Donald G.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Silicon containing doai

5142318, 5142325, 514316, 544 79, 546 14, 546187, A61K 31445

Patent

active

053045483

ABSTRACT:
Bivalent ligand compounds synthesized from a tether composition joining two heterocyclic groups comprising furochromones, furobenzoxazinones, and benzobisdifurans. These compounds show pharmacological activity in blocking ACAT enzymes which are major regulators of cholesterol metabolism. The compounds also show activity in lowering plasma triglycerides and elevating HDL cholesterol. They are useful in the prevention or treatment of the constriction or obstruction of arterial vessels, atherosclerosis, hyperlipidemia, hypertriglyceridemia, chylomicronemia, and pancreatitis.

REFERENCES:
patent: 3816467 (1974-06-01), Wright
patent: 4284569 (1981-08-01), Gammill
patent: 4304722 (1981-12-01), Gammill
patent: 4412071 (1983-10-01), Gammill
patent: 4434295 (1984-02-01), Gammill
patent: 4540798 (1985-09-01), Gammill
patent: 5162360 (1992-11-01), Creswell et al.
patent: 5180717 (1993-01-01), Gammill et al.
patent: 5185358 (1993-03-01), Creswell
Lancet 2, "W.H.O. Cooperative Trial on Primary Prevention on Ischemic Heart Disease Using Colifibrate to Lower Serum Cholesterol: Mortailty Follow-Up," pp. 379-385 (1980).
Lois M. Zucker, Annals New York Academy of Sciences, "Hereditary Obesity in the Rat Associated with Hyperlipemia", pp. 447-457 (1965).
Wayne S. Barry et al., "Plasma Triglycerides in Genetically Obese Rates", Metabolism, vol. 18, No. 10, pp. 833-839 (Oct. 1969).
Gustav Schonfeld, et al., "Characterization of the Plasma Lipoproteins of the Genetically Obese Hyperlipoproteinemic Zucker Fatty Rat", Journal of Lipid Research, vol. 15, pp. 457-464 (1974).
Christine Simonelli, et al., "Effect of Clofibrate on in vivo Triglyceride Production and Clearance in Genetically Hyperlipemic Rats", Atherosclerosis, 29, pp. 269-275 (1978).
A. Fontbonne, et al., "Hypertriglyceridaemia as a Rick Factor of Coronary Heat Disease Mortality in Subjects with Imparied Glucose Tolerance of Diabetes", Diabetologia, 32, pp. 300-304 (1989).
Lars A. Carlson, et al., "Risk Factors for Ischaemic Heart Disease in Men and Women;", Acta Med Scand, 218, pp. 207-211 (1985).
William P. Castelli, MD, "The Triglyceride Issue: A View from Framingham", American Heat Journal, vol. 112, No. 2, pp. 432-437 (1986).
Basil M. Rifkind, MD, "High-Density Lipoprotein Cholesterol and Coronary Artery Disease: Survey of the Evidence", The American Journal of Cardiology, vol. 66, pp. 3A-6A (Sep. 4, 1990).
Peter W. F. Wilson, MD, "High-Density Lipoprotein, Low-Density Lipoprotein and Coronary Artery Disease", The American Journal of Cardiology, vol. 66, pp. 7A-10A (Sep. 4, 1990).
W. Virgil Brown, MD, "Clinical Trials Including an Update on the Helsinki Heart Study", The American Journal of Cardiology, vol. 66, pp. 11A-15A (Sep. 4, 1990).
Frank P. Bell, et al., "U-73,482: A Novel ACAT Inhibitor that Elevates HDL-Cholesterol, Lowers Plasma Triglyceride and Facilitates Hepatic Cholesterol Mobilization in the Rat", Atherosclerosis, 92, pp. 115-122 (1992).
Ronald B. Gammill, et al., "Antiatherosclerotic Agents, A Structural Novel Bivalent Inhibitor of AcylCoA:Cholesterol O-Acyltransferase with Systemic Activity", Jour. Med. Chem. vol. 33, pp. 2685-2687 (May 10, 1990).
Frank P. Bell et al., "U-73,482, a Novel Symstemically Acting Inhibitor of AcylCoA:Cholesterol Acyltransferase (ACAT) With Potent Hypotriglyceridemic and HDL-Elevating Effects", 63rd Scientific Seesions Abstract Form, Medical Research, Nursing Research, American Heart Association, pp. 3-4 (Nov. 1990).
Kossakowski et al. Chem. Abstr vol. 109 Entry 149179s (1988).

Affiliated with

Also associated with

Rating

Bivalent ligands effective for blocking ACAT enzyme for lowering does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Bivalent ligands effective for blocking ACAT enzyme for lowering, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Bivalent ligands effective for blocking ACAT enzyme for lowering will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-19820