Hydrazino 1H-imidazoquinolin-4-amines and conjugates made therefrom

Patent metadata

Field	Value
Publication number	US-9585968-B2
Application number	US-201514826754-A
Country	US
Kind code	B2
Filing date	Aug 14, 2015
Priority date	Jun 3, 2011
Publication date	Mar 7, 2017
Grant date	Mar 7, 2017

Abstract

1H-Imidazo[4,5-c]quinolin-4-amines substituted at the 1-position with a substituent bearing a hydrazinobenzamide or hydrazinonicotinamide, a salt thereof, or a protected hydrazinobenzamide or hydrazinonicotinamide and conjugates made from such compounds are disclosed. Pharmaceutical compositions containing the compound or the conjugate, methods of making a conjugate, and methods of use of the compounds or conjugates as immunomodulators for inducing cytokine biosynthesis in an animal and for vaccinating an animal are also disclosed.

First claim

What is claimed is:

1. A conjugate comprising a reaction product of an aldehyde-bearing antigen and a compound or salt of formula:

wherein:
X is alkylene having up to 8 carbon atoms optionally interrupted or terminated by —O—;
R 2 is hydrogen, alkyl, alkoxyalkylenyl, alkylaminoalkylenyl, or hydroxyalkylenyl;
A is CH or N:
R is halogen, hydroxyl, alkyl, haloalkyl, or alkoxy; and
n is an integer from 0 to 4;

or a pharmaceutically acceptable salt thereof.

2. The conjugate of claim 1 , wherein n is 0.

3. The conjugate of claim 1 , wherein R 2 is methyl, ethyl, propyl, butyl, ethoxymethyl, methoxymethyl, or 2-methoxyethyl.

4. The conjugate of claim 1 , wherein X is —O—C 3-8 alkylene.

5. The conjugate of claim 1 , wherein X is —O—C 3-5 alkylene.

6. The conjugate of claim 1 , wherein X is C 3-8 alkylene.

7. The conjugate of claim 1 , wherein X is C 3-5 alkylene.

8. The conjugate of claim 1 , wherein the antigen is a protein, glycoprotein, peptide, recombinant protein, recombinant glycoprotein, or recombinant peptide.

9. The conjugate of claim 1 , wherein the antigen is a vaccine.

10. The conjugate of claim 9 , wherein the vaccine is selected from the group consisting of a live viral immunogen, an attenuated viral immunogen, a live bacterial immunogen, an attenuated bacterial immunogen, an inactivated viral immunogen, an inactivated tumor-derived immunogen, an inactivated inprotozoal immunogen, an inactivated organism-derived immunogen, an inactivated fungal immunogen, an inactivated bacterial immunogen, a cellular vaccine, or a DNA vaccine.

11. The conjugate of claim 9 , wherein the vaccine is for BCG, cholera, plague, typhoid, hepatitis A, B, or C, influenza A or B, parainfluenza, polio, rabies, measles, mumps, rubella, yellow fever, tetanus, diphtheria, hemophilus influenza b, tuberculosis, meningitis, pneumococcal, adenovirus, HIV, chicken pox, cytomegalovirus, dengue, fowl plague, HSV-1 or HSV-2, hog cholera, Japanese encephalitis, respiratory syncytial virus, rotavirus, papilloma virus, severe acute respiratory syndrome, or anthrax.

12. A method of vaccinating an animal, the method comprising administering an effective amount of the conjugate of claim 11 to the animal.

13. A method of stimulating an antigen-specific response in an animal, the method comprising administering an effective amount of the conjugate of claim 11 to the animal.

14. A method of vaccinating an animal, the method comprising administering an effective amount of the conjugate of claim 10 to the animal.

15. A method of stimulating an antigen-specific response in an animal, the method comprising administering an effective amount of the conjugate of claim 10 to the animal.

16. A method of vaccinating an animal, the method comprising administering an effective amount of the conjugate of claim 9 to the animal.

17. A method of stimulating an antigen-specific response in an animal, the method comprising administering an effective amount of the conjugate of claim 9 to the animal.

18. A method of inducing cytokine biosynthesis in an animal, the method comprising administering an effective amount of the conjugate of claim 1 to the animal.

19. A method of treating a viral disease in an animal, the method comprising administering an effective amount of the conjugate of claim 1 to the animal.

Assignees

• 3M Innovative Properties Co

Inventors

• Wightman Paul D

Classifications

• A61P31/18

  for HIV · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P31/20

  for DNA viruses · CPC title