Fucosidase inhibitors

• US 5,100,797 A
• Filed: 06/27/1989
• Issued: 03/31/1992
• Est. Priority Date: 06/27/1989
• Status: Expired due to Term

• Current Assignee: Monsanto Company (Bayer AG)
• Original Assignee: Monsanto Company (Bayer AG)
• Inventors: Namgoong, Sung K., Fleet, George W. J.
• Primary Examiner(s): Brown, Johnnie R.
• Assistant Examiner(s): Carson, Nancy S.
• Application Number:
  US07/371,943
• Time in Patent Office: 1,008 Days
• Field of Search: 536/1.1, 536/18.7, 536/55.3, 435/200, 514/315, 514/413, 514/23, 546/184, 546/242
• US Class Current: 435/200
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 211/46 having a hydrogen atom as the second substituent in position 4
• CPC Class Codes: C07D 491/04 Ortho-condensed systems
• CPC Class Codes: C07D 493/04 Ortho-condensed systems
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The synthesis of the novel fucosidase inhibitors, β-L-homofuconojirimycin and related 1-β-C-substituted deoxymannojirimycins, is disclosed.

Claims

1. A fucosidase inhibitor selected from the group consisting of 1-β

-C-substituted deoxymannojirimycins in which the 1-β

-C substituent is an alkyl group having from one to six carbon atoms or phenyl.

5. A method of inhibiting α

-L-fucosidase in a biological fluid comprising subjecting said biological fluid containing Δ

-L-fucosidase to an inhibitory effective amount of a compound of claim 1.

6. A method for the production of a β

-1-C-substituted deoxymannojirimycin of claim 1 comprising reacting 5-azido-6-O-tert-butyldimethylsilyl-5-deoxy-2,3-O-isopropylidene-D-mannono-1,4-lactone with an alkylating reagent selected from the group consisting of methyl lithium, vinyl magnesium bromide and phenyl magnesium bromide to give a 1-C-adduct of said 5-azido-6-O-tert-butyldimethylsilyl-5-deoxy-2,3-O-isopropylidene-D-mannono-1,4-lactone followed by catalytic hydrogenation of said adduct to give a corresponding hydroxyl-protected β

-1-C-substituted deoxymannojirimycin and then hydrolytic removal of the silyl and isopropylidene protecting groups from said hydroxyl-protected β

-1-C-substituted deoxymannojirimycin.

2. β

-1-C-methyl deoxymannojirimycin.

3. β

-1-C-ethyl deoxymannojirimycin.

4. β

-1-C-phenyl deoxymannojirimycin.