Method for inhibiting sialidase activity

• US 5,512,470 A
• Filed: 05/19/1995
• Issued: 04/30/1996
• Est. Priority Date: 06/25/1992
• Status: Expired due to Fees

• Current Assignee: E. I. du Pont de Nemours and Company (Corteva, Inc.)
• Original Assignee: E. I. du Pont de Nemours and Company (Corteva, Inc.)
• Inventors: Sabesan, Subramaniam
• Primary Examiner(s): Robinson, Douglas W.
• Assistant Examiner(s): Fonda, Kathleen Kahler
• Application Number:
  US08/444,593
• Time in Patent Office: 347 Days
• Field of Search: 435/200, 514/25, 514/53, 536/17.2, 536/53, 536/123.13
• US Class Current: 435/200
• CPC Class Codes: C07H 15/10 containing unsaturated carbon-to-carbon bonds
• CPC Class Codes: C07H 15/14 attached to a sulfur, selenium or tellurium atom of a saccharide radical
• CPC Class Codes: C07H 23/00 Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12 esters with inorganic acids C07H11/00; metal salts, see parent compounds
• CPC Class Codes: C07H 3/06 Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages

Abstract

Novel NeuAc-Gal dissacharide sialidase substrates and inhibitors which are locked into rigid conformation by the attachment of an alkyl group at the C-6 arm of the galactose core are provided. Also provided is a method for the inhibition of sialidase activity.

Claims

1. A method for inhibiting sialidase activity comprising contacting sialidase with a compound of Formula I ##STR8## wherein R is H or C₁ to C₂₀ hydrocarbyl or substituted hydrocarbyl;

R¹ is H, a C₁ to C₂₀ alkyl, a mono, di or polyvalent cation of an alkali metal, alkaline earth metal or transition metal, or an ammonium or substituted ammonium ion;

X is O, S, CR⁴ R⁵ or NR⁶, wherein R⁴, R⁵, R⁶ are each independently H or a C₁ to C₂₀ hydrocarbyl or substituted hydrocarbyl;

R² is a C₁ to C₂₀ hydrocarbyl or substituted hydrocarbyl;

R³ and R^3'"'"' are H, OH, a C₁ to C₂₀ alkoxy or substituted alkoxy, a mono, di or oligosaccharide, or a C₁ to C₂₀ alkylideneoxy taken together with R^7'"'"' when R^7'"'"' is not H;

provided that one of R³ or R^3'"'"' must be H but R³ and R^3'"'"' may not both be H;

R⁷ and R^7'"'"' are independently H, a C₁ to C₂₀ acyl, a C₁ to C₂₀ alkyl, or a C₁ to C₂₀ alkylidene taken together with an adjacent R^3'"'"', R⁷ or R7'"'"'; and

R⁸ is H, a C₁ to C₂₀ acyl, or a C₁ to C₂₀ alkyl.

2. The process of claim 1 wherein in formula I R is methyl;

R¹ is Na or CH₃ ;

R² i s CH₃ ;

R⁸ is H or acetyl;

R⁷ is H or alkylidene taken together with R³ '"'"' ;

R^7'"'"' is acetyl or benzyl;

R³ is OH when R^3'"'"' is H;

R^3'"'"' is OH when R³ is H; and

X is S.