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