Tricyclic P2-ligand containing potent HIV-protease inhibitors against HIV/AIDS
Various embodiments relate to a compound of the formula (I) and (II), wherein X, X 1 , X 2 , X 3 , and R 1 -R 4 are defined herein, as well as pharmaceutical compositions comprising compounds of the formula (I) and/or (II) and methods of treating an HIV infection comprising administering a therapeutically effective amount of one or more compounds of formula (I) and/or (II), or a pharmaceutical composition comprising compounds of the formula (I) and/or (II), to a patient in need thereof.
1. A method for treating an HIV infection comprising administering a therapeutically effective amount of one or more compounds of the formula (I):
or a pharmaceutically acceptable salt, polymorph, or solvate thereof, wherein:
n is an integer from 0 to 3; X is (—CHR 5 —) m or —O—, wherein m is 1 or 2 and each R 5 is, independently H, alkyl or alkoxy;
X 1 , X 2 , and X 3 are each, independently, (—CHR 5 —) m ;
R 1 is alkyl, alkoxy, aryl, heterocyclyl, halo, hydroxy or amino;
R 2 is alkyl;
R 3 is aryl, benzthiazole, benzoxazole, benzofuranyl or indolyl; and
R 4 is H, alkyl or alkoxy;
to a subject in need thereof.
2. The method of claim 1 , wherein:
X 1 is (—CHR 5 —) m , wherein m is 2;
X 2 is (—CHR 5 —) m , wherein in is 1;
X 3 is (—CHR 5 —) m , wherein m is 1; and
wherein each R 5 is independently H, alkyl or alkoxy.
3. The method of claim 1 , wherein:
X 1 is (—CHR 5 —) m , wherein m is 1;
X 2 is (—CHR 5 —) m , wherein m is 1;
X 3 is (—CHR 5 —) m , wherein m is 2; and
wherein each R 5 is independently H, alkyl or alkoxy.
4. The method of claim 1 , wherein X is O.
5. The method of claim 1 , wherein X is (—CHR 5 —) m , wherein m is 1 and R 5 is H, alkyl or alkoxy.
6. The method of claim 1 , wherein R 4 is H or alkoxy.
7. The method of claim 1 , wherein the compound of the formula (I) is a compound of the formula:
or a pharmaceutically acceptable salt, polymorph, prodrug, solvate or clathrate thereof, wherein n, R 1 , R 2 , R 3 , and R 4 are as defined in claim 1 .
8. The method of claim 1 , wherein n is 0.
9. The method of claim 1 , wherein R 2 is unsubstituted alkyl.
10. The method of claim 1 , wherein R 3 is aryl, benzthiazole or benzoxazole.
11. The method of claim 10 , wherein R 3 is phenyl.
12. The method of claim 10 , wherein R 3 is:
13. The method of claim 12 , wherein R 3 is:
14. The method of claim 10 , wherein R 3 is:
R 6 is alkyl, alkylamino, cycloalkylamino, cycloalkyl heterocycloamino, heterocyclo cycloalkylamino or heterocycloamino; and
X 4 is S or O.
15. The method of claim 1 , wherein the compound of formula (I) is at least one of:
or a pharmaceutically acceptable salt, polymorph, or solvate thereof.