Polycationic compounds and uses thereof
Aspects of the present invention relate to compounds and methods useful in modulating angiogenesis and methods of treating or preventing diseases associated with angiogenesis by administering a polycationic compound. The present invention relates to methods of use and compositions for inhibiting angiogenesis-mediated disorders in mammals including animals and humans. Additionally, this invention relates to the combined use of polycations with other anti-angiogenesis agents for the treatment of different angiogenesis-mediated disorders. Additionally, those polycationic compounds can be used with various anti-inflammatory and cytotoxic agents as well as with radio-therapeutic agents in cancer patients to prevent and treat tumor growth and metastasis.
1. An arylamide compound of the formula
wherein:
X is O or S;
R 1 is C 1 -C 9 straight or branched chain alkyl, optionally substituted with one or more —NH 2 or
Y is a bond or
Z is a bond or
R 2 is hydrogen or C 1 -C 9 straight or branched chain alkyl, optionally substituted with one or more —NH 2 or
or R 2 is —X—R 1 ;
R 3 is methylene or
wherein the methylene is substituted with C 1 -C 9 straight or branched chain alkyl, wherein the C 1 -C 9 straight or branched chain alkyl is optionally substituted with one or more —NH 2 or
n is 2-10; and
m is 1 or 2.
2. An arylamide compound of the formula:
wherein:
X is O or S;
Y is O or S;
R 1 is H or —C(═O)-A, where A is C 1 to C 9 straight or branched alkyl, where A is optionally substituted with one or more —NH 2 , —N(CH 3 ) 2 or
R 2 is C 1 to C 9 straight or branched alkyl, optionally substituted with one or more —NH 2 , —N(CH 3 ) 2 or
R 3 is C 1 to C 9 straight or branched alkyl, optionally substituted with one or more —NH 2 , —N(CH 3 ) 2 or
and
R 4 is H, −B, or —C(═O)—O—B, where B is C 1 to C 9 straight or branched alkyl.
3. The arylamide compound of claim 2 of the formula:
wherein:
R 1 is
4. The arylamide compound of claim 2 of the formula:
5. The arylamide compound of claim 2 of the formula:
6. A composition comprising an arylamide compound of claim 1 and a pharmaceutically acceptable carrier.
7. The composition of claim 6 further comprising another angiogenesis inhibitor.
8. A method of inhibiting angiogenesis in an animal in need thereof comprising administering to the animal a therapeutically effective amount of an arylamide compound of claim 1 .
9. A method of antagonizing heparin in an animal in need thereof comprising administering to the animal a therapeutically effective amount of an arylamide compound of claim 1 .
10. A method of inhibiting angiogenesis in an animal in need thereof comprising administering to the animal a therapeutically effective amount of an arylamide compound of claim 2 .
11. A method of inhibiting angiogenesis in an animal in need thereof comprising administering to the animal a therapeutically effective amount of an arylamide compound of claim 3 .
12. A method of inhibiting angiogenesis in an animal in need thereof comprising administering to the animal a therapeutically effective amount of an arylamide compound of claim 4 .
13. A method of inhibiting angiogenesis in an animal in need thereof comprising administering to the animal a therapeutically effective amount of an arylamide compound of claim 5 .
14. A method of antagonizing heparin in an animal in need thereof comprising administering to the animal a therapeutically effective amount of an arylamide compound of claim 2 .
15. A method of antagonizing heparin in an animal in need thereof comprising administering to the animal a therapeutically effective amount of an arylamide compound of claim 3 .
16. A method of antagonizing heparin in an animal in need thereof comprising administering to the animal a therapeutically effective amount of an arylamide compound of claim 4 .
17. A method of antagonizing heparin in an animal in need thereof comprising administering to the animal a therapeutically effective amount of an arylamide compound of claim 5 .
18. An arylamide compound chosen from
19. A method of inhibiting angiogenesis in an animal in need thereof comprising administering to the animal a therapeutically effective amount of an arylamide compound of claim 18 .
20. A method of antagonizing heparin in an animal in need thereof comprising administering to the animal a therapeutically effective amount of an arylamide compound of claim 18 .