Compounds that stimulate glucose utilization and methods of use

Details Compounds that stimulate glucose utilization and methods of use Compounds that stimulate glucose utilization and methods of use

2006-08-01

2006-08-01

Davis, Zinna Northington (Department: 1625)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Ester doai

C514S529000, C560S123000, C560S124000

Reexamination Certificate

active

07084173

ABSTRACT:
The invention provides novel compounds of the Formula (I) that stimulate rates of glucose oxidation in myocardial cells. The invention also relates to pharmaceutical compositions comprising compounds capable of stimulation of glucose oxidation, methods for increasing glucose oxidation rates in myocardial cells, and methods of treatment of myocardial ischemiawhereinW is C1–C6alkyl, halogen, or aryl;Cyc is C3or C4cycloalkyl;p is 0–3 for Cyc being C4cycloalkyl and p=0–2 for Cyc being C3cycloalkyl;Y is O, S, or NR, where R═H, alkyl or aryl;X is O, S, NR, or CR3R4;Z is H, alkyl, cycloalkyl, aryl or (cyclo)alkylcarbonyl;R1is H, alkyl, aryl or O;R2is H, alkyl or aryl;R3and R4are, independently, H, alkyl or aryl; andn is an integer from 1 to 10; or a pharmaceutically acceptable salt, ester or prodrug thereof.

REFERENCES:
patent: 3306727 (1967-02-01), Neighbors
patent: 3926860 (1975-12-01), Chappell
patent: 3957849 (1976-05-01), Henrick et al.
patent: 4000315 (1976-12-01), Henrick et al.
patent: 4935422 (1990-06-01), Patil et al.
patent: WO 02/085294 (2002-10-01), None
patent: WO 03/082800 (2003-10-01), None
Barak, C., et al., Effects of dichloroacetate on mechanical recovery and oxidation of physiologic substrates after ischemia and reperfusion in the isolated heart, J Cardiovasc Pharmacol 31: 336-44., 1998.
Barbour, R.L., et al.,.Use of gated perfusion to study early effects of anoxia on cardiac energy metabolism: A new31P NMR methodBiochemistry1923:6503-6062, 1984.
Bersin, et al., Dichloroacetate as metabolic therapy for myocardial ischemia and failure, American Heart Journal, 134(5)(Part 1):841-855 (1997).
Burger, et al., Database Crossfile Beilstein 'Online! Beilstein Institute zur Forderung der Chemischen Wissenschaften, Frankfurt am Main, DE; Database accession No. 2576757, XP002248454 (Abstract) J. Med. Chem.., vol. 6, 1963, pp. 221-227.
Calderon, et al., Database Crossfire Beilstein 'Online! Beilstein Institute zur Forderung der Chemischen Wissenschaften, Frankfurt am Main, DE; Database accession No. 7079339 XP002248456 (Abstract) J. Med. Chem., vol. 37, No. 15, 1994, pp. 2285-2291.
Chen, T.M., et al., Effects of insulin on glucose uptake by rat hearts during and after coronary flow reduction, Am J Physiol 273: H2170-7., 1997.
Database CA 'Online! Chemical Abstracts Service, Columbus, Ohio, US; Henrick, et al., “Ovicidal activity and its relation to chemical structure for the two-spotted spider mite (Tetranychus urticae Koch) in a new class of miticides contaiing the cyclopropyl group”, retrieved from STN Database accession No. 85:105335 CA XP002249230 s. RN 60128-48-5, RN 60128-46-3 abstract & Journal of Agricultural and Food Chemistry (1976), 24(5), 1023-9.
Fraser, H., et al., Assessment of glycogen turnover in aerobic, ischemic, and reperfused working rat hearts, Am J Physiol 275: H1533-41, 1998.
Fraser, H., et al., Alteration of glycogen and glucose metabolism in ischaemic and post-ischaemic working rat hearts by adenosine A1receptor stimulation, Br J Pharmacol 128: 197-205, 1999.
Gamble, J., et al., Glycolysis and glucose oxidation during reperfusion of ischemic hearts from diabetic rats, Biochimica et Biophysica Acta 1225: 191-9, 1994.
Itoi, T., et al., The contribution of glycolysis, glucose oxidation, lactate oxidation, and fatty acid oxidation to ATP production in isolated biventricular working hearts from 2-week-old rabbits, Pediatric Research 34: 735-41, 1993.
Jonassen, A.K., et al., Glucose-insulin-potassium reduces infarct size when administered during reperfusion,Cardiovasc Drugs Ther14: 615-23., 2000.
Kantor, P.F., et al., The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochodrial long-chain 3-ketoacryl coenzyme A thiolase, Circulation Research. 86: 580-8, 2000.
King, L.M., et al., Glucose delivery is a major determinant of glucose utilisation in the ischemic myocardium with a residual coronary flow, Cardiovasc Res 39: 381-92., 1998.
Kudo, N., et al., Characterization of 5′AMP-activated protein kinase activity in the heart and its role in inhibiting acetyl-CoA carboxylase during reperfusion following ischemia, Biochimica et Biophysica Acta 1301: 67-75, 1996.
Kudo, N., et al., High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5′-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase, Journal of Biological Chemistry 270(29): 17513-20, 1995.
Lopaschuk, G.D., et al., Plasma fatty acid levels in infants and adults after myocardial ischemia, Am Heart J 128: 61-7, 1994.
Lopaschuk, G.D., et al., Regulation of carbohydrate metabolism in ischemia and reperfusion, Am Heart J 139: S115-9., 2000.
Lopaschuk, G.D., et al., Alterations in fatty acid oxidation during reperfusion of the heart after myocardial ischemia, Am J Cardiol 80: 11A-16A, 1997.
Lopaschuk, G.D., et al., Treating ischemic heart disease by pharmacologically improving cardiac energy metabolism, Am J Cardiol 82: 14K-17K., 1998.
Lopaschuk, G.D., et al., Response of isolated working hearts to fatty acids and carnitine palmitoyltransferase I inhibition during reduction of coronary flow in acutely and chronically diabetic rats, Circ Res 65: 378-87, 1989.
Lopaschuk, G.D., et al., Glucose and palmitate oxidation in isolated working rat hearts reperfused after a period of transient global ischemia, Circ Res 66: 546-53, 1990.
Lopaschuk, G.D., et al., Glucose metabolism in the ischemic heart, Circulation 95: 313-5., 1997.
Lopaschuk, G.D., et al., Optimizing cardiac energy metabolism: How can fatty acid and carbohydrate metabolism be manipuated?, Coron Artery Dis 12: S8-11., 2001.
Lopaschuk, G.D., et al., Measurements of fatty acid and carbohydrate metabolism in the isolated working rat heart, Molecular & Cellular Biochemistry 172: 137-47, 1997.
Lopaschuk, G.D., et al., Glucose oxidation is stimulated in reperfused ischemic hearts with the carnitine palmitoyltransferase 1 inhibitor, Etomoxir, Molecular & Cellular Biochemistry 88: 175-9, 1989.
McCormack, J.G., et al., Ranolazine stimulates glucose oxidation in normoxic, ischemic, and reperfused ischemic rat hearts, Circulation 93: 135-42., 1996.
McCormack, J.G., et al., Ranolazine: A novel metabolic modulator for the treatment of angina, Gen Pharmacol 30(5): 639-45., 1998.
McVeigh, J.J., et al, Dichloroacetate stimulation of glucose oxidation improves recovery of ischemic rat hearts, American Journal of Physiology 259: H1079-85, 1990.
Nicholl, T.A., et al., Effects of free fatty acids and dichloroacetate on isolated working diabetic rat heart, American Journal of Physiology 261: H1053-9, 1991.
Pogatsa, G., Metabolic energy metabolism in diabetes: therapeutic implications, Coron Artery Dis 12: S29-33., 2001.
Saddik, M., et al., Myocardial triglyceride turnover during reperfusion of isolated rat hearts subjected to a transient period of global ischemia, J Bio Chem. 1992; 267(6):3825-3831.
Stanley, W.C., et al., Cardiac energetics during ischaemia and the rationale for metabolic interventions, Coron Artery Dis 12: S3-7., 2001.
Taniguchi, M., et al., Dichloroacetate improves cardiac efficiency after ischemia independent of changes in mitochondrial proton leak, Am J Physiol Heart Circ Physiol 280: H1762-9., 2001.
Vaghaiwalla, F., et al., Trimetazidine-induced enhancement of myocardial glucose utilization in normal and ischemic myocardial tissue: An evaluation by positron emission tomography, Am J Cardiol 82: 42K-49K., 1998.
Wambolt, R.B., et al., Dichloroacetate improves postischemic function of hypertrophied rat hearts, J Am Coll Cardiol 36: 1378-85., 2000.
Whitten, et al., Database Crossfire Beilstein 'Online! Beilstein Institute zur Forderung der Chemischen Wissenschaften, Frankfurt am Main, DE; Database accession No. 2040782 XP002248455 Abstract J. Med. Chem., vol. 39, No. 22, 1996, pp. 4354-4357.
Yamane, Y., et al., Stimulated glucose uptake in the ischemic border zone: Its dependence on glucose uptake in the norm

Affiliated with

Also associated with

Rating

Compounds that stimulate glucose utilization and methods of 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 Compounds that stimulate glucose utilization and methods of use, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compounds that stimulate glucose utilization and methods of use will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3644646