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

Patent metadata

Field	Value
Publication number	US-10406142-B2
Application number	US-201715450812-A
Country	US
Kind code	B2
Filing date	Mar 6, 2017
Priority date	Jun 3, 2011
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

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 of an antigen, the conjugate having at least one segment represented by formula:

wherein:
X is —O—C 3-8 alkylene, wherein the —O— is directly attached to the nitrogen of the imidazole ring;
R 2 is methyl, ethyl, propyl, butyl, ethoxymethyl, methoxymethyl, or 2-methoxyethyl;
A is CH or N;
R is halogen, hydroxyl, alkyl, haloalkyl, or alkoxy;
n is 0;
Z is a bond or —C(O)—NH—(CH 2 CH 2 O) p —CH 2 CH 2 —, wherein p is in a range from 1 to 50; and
the nitrogen atom indicated by N* is covalently bonded to the antigen;

or a pharmaceutically acceptable salt thereof.

2. The conjugate of claim 1 , wherein Z is a bond.

3. The conjugate of claim 1 , wherein Z is —C(O)—NH—(CH 2 CH 2 O) p —CH 2 CH 2 —, wherein p is in a range from 1 to 50.

4. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the conjugate of claim 1 .

5. The conjugate of claim 1 , wherein X is —O—CH 2 —CH 2 —CH 2 —CH 2 —, wherein the —O— is directly attached to the nitrogen of the imidazole ring.

6. The conjugate of claim 1 , wherein R 2 is butyl.

7. The conjugate of claim 1 , wherein A is N.

8. The conjugate of claim 7 , wherein X is —O—CH 2 —CH 2 —CH 2 —CH 2 —, wherein the —O— is directly attached to the nitrogen of the imidazole ring.

9. The conjugate of claim 8 , wherein R 2 is butyl.

10. The conjugate of claim 7 , wherein R 2 is butyl.

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

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

13. The conjugate of claim 12 , 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, and a DNA vaccine.

14. The conjugate of claim 12 , 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, haemophilus 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.

Assignees

• 3M Innovative Properties Co
• 3M Lnnovative Properties Company

Inventors

• Wightman Paul D

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/22

  for herpes viruses · CPC title