Glycohydrolase inhibitors, their preparation and use thereof

Details Glycohydrolase inhibitors, their preparation and use thereof Glycohydrolase inhibitors, their preparation and use thereof

1994-09-07

1998-12-01

Wilson, James O.

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 173, 514299, 514315, 514328, 546112, 546116, 546138, 546183, 546220, 546224, C07H 1500

Patent

active

058441026

ABSTRACT:
A compound of the formula ##STR1## wherein n, m, and p, which may be the same or different, are a number between 0 and 5; q is a number between 0 and 10; R.sub.1, R.sub.2 R.sub.3 R.sub.4 and R.sub.5, which may be the same or different, are a hydrogen, a hydroxyl, a halogen, a hydrocarbon or an O-hydrocarbon group having between 1 and 6 carbons which is aliphatic, alicyclic or aromatic, or a glycosyl group; and R.sub.4 is a glycosyl group, is disclosed. Nitrogen oxides of such compounds are also included. These novel compounds have been found to be potent glycohydrolase inhibitors. Processes for preparing these novel compounds and methods for their use in the treatment of diabetes mellitus are also provided.

REFERENCES:
patent: 3235541 (1966-02-01), Carlson
patent: 4788335 (1988-11-01), Wagner et al.
patent: 4963355 (1990-10-01), Kim et al.
patent: 4970317 (1990-11-01), Margolin et al.
patent: 5156965 (1992-10-01), Schochetman et al.
patent: 5157116 (1992-10-01), Ducep et al.
patent: 5194585 (1993-03-01), Paul et al.
patent: 5229272 (1993-07-01), Paul et al.
Cerny et al, "Synthesis with Anhydro Sugars. V. Preparation of 2,4-Di-O-Substituted 1,6-Anhydro-.beta.-D-Hexopyranos-3-Uloses and Their Isomerization and Reduction," Collection Czechoslov. Chem. Commun., vol. 33, pp. 1143-1156 (1968).
Cogoli et al, "A Probable Oxocarbonium Ion in the Reaction Mechanism of Small Intestinal Sucrase and Isomaltase," Jnl. Biological Chem., vol. 250, No. 19, pp. 7802-7809 (Oct. 1975).
Dimitriadis et al, ".alpha.-Glucosidase Inhibition Improves Postprandial Hyperglycemia and Decreases Insulin Requirements in Insulin-Dependent Diabetes Mellitus," Metabolism, vol. 34, No. 3, pp. 261-265 (Mar. 1985).
Eis et al, "Mechanism and Synthetic Utility of Boron Trifluoride Etherate Promoted Organolithium Additions," J. Am. Chem. Soc., vol. 106, No. 12, pp. 3693-3694 (1984).
Kajimoto et al, "Enzyme-Catalyzed Aldol Condensation for Asymmetric Synthesis of Azasugars, Evaluation, and Modeling of Glycosidase Inhibitors," J. Am. Chem. Soc., vol. 113, No. 16, pp. 6187-6196 (1991).
Inghardt et al, "Oxirane Ring Opening of Anhydrosugars with Alkynyl-and Alkenylaluminates," J. of Synthetic Organic Chem., No. 4, pp. 285-291 (Apr. 1990).
Lardinois et al, "Acarbose Treatment of Non-Insulin-Dependent Diabetes Mellitus," Arch Intern Med, vol. 144, pp. 345-347 (Feb. 1984).
G. Legler, "Glycoside Hydrolases: Mechanistic Information from Studies with Reversible and Irreversible Inhibitors," Advances in Carbohydrate Chem. and Biochem., vol. 48, pp. 319-384, Academic Press, Inc.
Lipshutz et al, "2-Thienyl(Cyano)Copper Lithium. A Lower Order, Stable `Cuprate in a Bottle` Precursor to Higher Order Reagents," Tetrahedron Letters, vol. 28, No. 9, pp. 945-948 (1987).
Papandreou et al, "Amidine, Amidrazone, and Amidoxime Derivatives of Monosaccharide Aldonolactams: Synthesis and Evaluation as Glycosidase Inhibitors," J. Am. Chem. Soc., vol. 115, No. 25, pp. 11682-11690 (Dec. 1993).
Quaroni et al, "Affinity Labeling of the Active Sites in the Sucrase-Isomaltase Complex from Small Intestine," Jnl. of Biological Chem., vol. 249, No. 20, pp. 6424-6433 (1974).
Reymond et al, "Antibody Catalysis of Glycosidic Bond Hydrolysis," Angew. Chem. Int. Ed. Engl., vol. 30, No. 12, pp. 1711-1713 (1991).
Rhinehart et al, "Inhibition of Intestinal Disaccharidases and Suppression of Blood Glucose by a New .alpha.-Glucohydrolase Inhibitor--MDL 25,637," Jnl. of Pharmacology and Experimental Therapeutics, vol. 241, No. 3, pp. 915-920 (1987).
Robinson et al, "Castanospermine-Glucosides are Potent, Selective, Long-Acting Sucrase Inhibitors," Jnl. of Pharmacology and Experimental Therapeutics, vol. 251, No. 1, pp. 224-229 (1989).
Robinson et al, "New Potent .alpha.-Glucohydrolase Inhibitor MDL 73945 With Long Duration of Action in Rats," Diabetes, vol. 40, pp. 825-830 (Jun. 1991).
W.C. Still, "Stannylation/Destannylation. Preparation of .alpha.-Alkoxy Organolithium Reagents and Synthesis of Dendrolasin Via A Carbinyl Carbanion Equivalent," Jnl. Amer. Chem. Soc., vol. 100, No. 5, pp. 1481-1487 (Mar. 1978).
Winchester et al, "Amino-Sugar Glycosidase Inhibitors: Versatile Tools for Glycobiologists," Glycobiology, vol. 2, No. 3, pp. 199-210 (Jun. 1992).
J.B. Wright, "The Reaction of Sulfamide with .alpha.-and -62 -Diketones. The Preparation of 1,2,5-Thiadiazole 1,1-Dioxides and 1,2,6-Thiadiazine 1,1-Dioxides," Reaction of Sulfamide with .alpha.-And .beta.-Diketones, vol. 29, pp. 1905-1909, (Jul. 1964).
W. Dong et al., Design of Catalytic Antibodies for Carbohydrate Synthesis, Journal of Cellular Biochemistry, Supplement 18D, 194, T200 (Feb. 26-Apr. 17, 1994).
T.M. Jespersen et al., "Isofagomine, a Potent, New Glycosidase Inhibitor", Angew. Chem. Int. Ed. Engl., 33, No. 17, 1778-1779 (1994).

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