Novel compounds and methods for synthesis and therapy

• US 20040053999A1
• Filed: 07/28/2003
• Published: 03/18/2004
• Est. Priority Date: 09/17/1997
• Status: Abandoned Application

• Current Assignee: Choung U. Kim, Hongtao Liu, Matthew Andrew Williams, Michael J.M. Hitchcock, Norbert W. Bischofberger, Roger G. Mills, Terrence C. Dahl, Willard Lew
• Original Assignee: Choung U. Kim, Hongtao Liu, Matthew Andrew Williams, Michael J.M. Hitchcock, Norbert W. Bischofberger, Roger G. Mills, Terrence C. Dahl, Willard Lew
• Inventors: Williams, Matthew A., Hitchcock, Michael J. M., Mills, Roger G., Lew, Willard, Kim, Choung U., Liu, Hongtao, Dahl, Terrence C., Bischofberger, Norbert W.
• Application Number:
  US10/628,773
• Publication Number:
  US 20040053999A1
• Time in Patent Office: Days
• US Class Current: 514/519
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00

Abstract

Novel compounds are described. The compounds generally comprise an acidic group, a basic group, a substituted amino or N-acyl and a group having an optionally hydroxylated alkane moiety. Pharmaceutical compositions comprising the inhibitors of the invention are also described. Methods of inhibiting neuraminidase in samples suspected of containing neuraminidase are also described. Antigenic materials, polymers, antibodies, conjugates of the compounds of the invention with labels, and assay methods for detecting neuraminidase activity are also described.

Claims

1. A pharmaceutical formulation comprising an enteric protectant and a compound of the formula:

2. The pharmaceutical formulation of claim 1 wherein E₁ is —

CO₂R₅;

G₁ is NH₂ or N₃;

T₁ is NHC(O)CH₃; and

U₁ is —

OR₄.

3. The pharmaceutical formulation of claim 2 wherein E₁ is C(O)OCH₂CH₃;

G₁ is NH₂;

T₁ is NHC(O)CH₃; and

U₁ is OCH(CH₂CH₃)₂.

4. The pharmaceutical formulation of claim 1 comprising a compound of the formula:

5. The pharmaceutical formulation of claim 4 wherein the compound further comprises a phosphate salt.

6. The pharmaceutical formulation of claim 1 comprising a compound of the formula:

7. The pharmaceutical formulation of claim 1 wherein the enteric protectant is selected from cellulose acetate phthalate polymer, methyl acrylate-methacrylic acid copolymer, cellulose acetate succinate polymer, hydroxypropylmethylcellulose phthalate polymer, polyvinyl acetate phthalate polymer, cellulose acetate trimellitate polymer, hydroxypropyl methylcellulose phthalate succinate polymer, methacrylic acid polymer, and methacrylic acid ester polymer.

8. The pharmaceutical formulation of claim 1 wherein the formulation is a tablet.

9. The pharmaceutical formulation of claim 1 wherein the formulation is a capsule.

10. A pharmaceutical formulation comprising a liquid suspension of enteric coated particles of a compound of claim 1.

11. A method of inhibiting the activity of neuraminidase comprising the step of contacting a sample suspected of containing neuraminidase with a pharmaceutical formulation of claim 1.

12. The method of claim 11 wherein the neuraminidase is influenza neuraminidase in vivo.

13. A method for the treatment or prophylaxis of influenza infection in a host comprising administering to the host a therapeutically effective amount of a pharmaceutical formulation of claim 1.