Guanidinyl-substituted polyamides useful for treating human papilloma virus

1. A compound of the formula:

G-(X) n -γ q -(X) m -A

or a pharmaceutically acceptable salt thereof, wherein

m is 5-12;

n is 4-10;

G is a guanidinyl radical is the formula

or its tautomer, wherein R 1 , R 2 , R 3 , or R 4 is H, alkyl, aryl or aralkyl;

each X is independently selected from 4-amino-2-carbonyl-N-methylimidazole (Im), 4-amino-2-carbonyl-N-methylpyrrole (Py) or β-alanine (β);

γ q is γ-aminobutyric acid (γ), 2,4-diaminobutyric acid (γ NH2 ), or H 2 N(CH 2 ) 2 CH(NHC(═O)NHR)CO 2 H, wherein R is —(CH 2 ) 3 —N(CH 3 )—(CH 2 ) 3 —NH 2 (γ NHR′ ) or —(CH 2 ) 3 —N(CH 3 ) 2 (γ NHR″ ); and

A is 3,3′-diamino-N-methyldipropylamine (Ta) or 3-(dimethylamino)propylamine (Dp).

2. A compound according to claim 1 , wherein G is tetramethylguanidinyl (TMG).

3. A compound according to claim 1 , wherein the polyamide compound is selected from the group consisting of:

TM-PyPyβPyPyβPyIm-γ NH2 -PyβPyPyβPyPyPyβPyPy-Ta;

TMG-PyPyPyβPyPyβPyIm-γ NHR -PyβPyPyβPyPyPyβPyβ-Ta;

TMG-PyPyPyβPyPyβPyIm-γ NH2 -PyβPyPyβPyPyPyβPyβ-Ta;

TMG-PyPyPyβPyPyβPy-γ NHR -PyPyPyβPyPyPyβPyβ-Ta;

TMG-PyPyPyβPyPyβPyIm-γ NH2 -PyβPyPyβPyPyPyβPyβ-Dp;

TMG-PyPyPyβPyPyβPy-γ NH2 -PyPyPyβPyPyPyβPyβ-Ta;

TMG-PyPyPyβPyPyβPy-γ NH2 PyPyPyβPyPyPyβPyβ-Dp;

TMG-PyβPyPyImβPyPy-γ-PyPyβPyPyPyβPyPyPyβ-Ta;

TMG-PyPyPyβPyPyβPy-γ NHR -PyPyPyβPyPyPyβPyβ-Dp;

TMG-PyβPyPyImβPyPy-γ-PyPyβPyPyPyβPyPyPyβ-Dp;

TMG-PyβPyPyPy-γ-PyPyβPyPyPyPyβ-Dp;

TMG-PyβPyPyPy-γ-PyPyβPyPyPyPyβ-Ta;

TMG-PyPyβPyPyPy-γ-PyPyβPyPyPyPyβ-Dp;

TMG-PyPyβPyPyPy-γ-PyPyβPyPyPyPyβ-Ta;

TMG-PyPyβPyPyImβPyPy-γ-PyPyβPyPyPyβPyPyPyβ-Ta;

TMG-PyPyβPyPyImβPyPy-γ-PyPyβPyPyPyβPyPyPyβ-Dp;

TMG-PyPyPyβPyPyβPyIm-γ-PyβPyPyβPyPyPyβPyβ-Ta;

TMG-PyPyPyβPyPyβPyIm-γ-PyβPyPyβPyPyPyβPyβ-Dp;

TMG-PyPyβPyPyβPyIm-γ-PyβPyPyβPyPyPyβPyβ-Dp;

TMG-PyPyβPyPyβPyIm-γ-PyβPyPyβPyPyPyβPyβ-Ta;

TMG-PyImβPyPy-γ-PyPyPyβPyPyPyβ-Ta;

TMG-PyPyβPyPyβPy-γ NH2 -PyPyPyβPyPyPyβPyβ-Ta;

TMG-PyPyβPyPyβPyIm-γ NH2 -Py βPyPyβPyPyPyβPyβ-Ta;

TMG-PyPyβPyPyβPy-γ-PyPyPyβPyPyPyβPyβ-Ta;

TMG-PyPyPyβPyPyβPy-γ-PyPyPyβPyPyPyβPyβ-Ta;

TMG-PyImPyIm-γ-PyPyPyPyβ-Ta;

TMG-PyImβIm-γ-PyβPyPyβ-Ta;

TMG-PyImPyIm-γ-PyβPyPyβ-Ta;

TMG-PyImβIm-γ-PyPyPyPyβ-Ta;

GUAN-PyImβImγPyβPyPyβ-Ta;

and pharmaceutically acceptable salts thereof.

4. A compound according to claim 1 , wherein γ q is (R)-2,4-diaminobutyric acid (γ NH2 ).

5. A compound according to claim 1 , wherein γ q is (S)-2,4-diaminobutyric acid (γ NH2 ).

6. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

7. The compound according to claim 1 , which is fluorescent or fluorescently labeled.

8. The compound according to claim 7 , of formula:

TMG-PyPyPyβPyPyβPyIm-γ-PyβPyPyβPyPyPyβPyβ-Ta-FAM; and pharmaceutically acceptable salts thereof.

9. A method of treating virus infected cells comprising contacting the cells with an effective amount of a compound of claim 1 .

10. The method according to claim 9 , wherein the infection is caused by a double-stranded DNA virus.

11. The method according to claim 9 , wherein the infection is caused by HPV, Epstein-Barr viruses, herpes viruses, adenoviruses, BK and pox viruses.

12. The method according to claim 9 , wherein the infection is caused by HPV16, HPV31, or HPV18.

13. A method of treating HPV in a subject comprising administering to the subject a pharmaceutical composition comprising an effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.