Trizol-1-OL analogs anti-retroviral latency drugs
In one aspect, the invention relates to triazol-1-ol compounds, analogs thereof, compositions comprising same, and methods of using same, alone or in combination with other agents, to reactivate latent retroviruses, and more particularly to reactivate latent HIV-1. Such compounds, compositions, and methods can be used, for example, in connection with diagnosing and/or treating a retrovirus, and more specifically HIV-1. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
1. A method of activating a latent retrovirus in a subject, the method comprising the step of administering to the subject an effective amount of a compound represented by a formula:
wherein n is 0 or 1;
wherein R 1 is selected from H, C1-C4 alkyl, C1-C6 aryl, C(O)Ar, C(O)N(CH 3 ) 2 , SO 2 N(CH 3 ) 2 , fluorenylmethyloxycarbonyl, N-((dimethylamino)methylene)-N-methylmethanaminium tetrafluoroborate, N-((dimethylamino)methylene)-N-methylmethanaminium hexafluorophosphate (V), tri(pyrrolidin-1-yl)phosphonium hexafluorophosphate (V), tris(dimethylamino)phosphonium hexafluorophosphate (V), 1-(pyrrolidine-1-ylmethylene)pyrrolidin-1-ium hexafluorophosphate (V), and 1-(piperidin-1-ylmethylene)piperidin-1-ium hexafluorophosphate (V);
wherein R 2 is selected from H and C1-C4 alkyl; and
wherein R 3 is selected from H and C1-C4 alkyl;
or wherein R 2 and R 3 are covalently bonded and, together with the intermediate atoms, comprise phenyl substituted with 0, 1, 2, or 3 groups independently selected from Cl, CH 3 , and NO 2 or unsubstituted pyridinyl.
2. The method of claim 1 , wherein the retrovirus is selected from HIV-1, HIV-2, SIV, XMRV, HTLV-1, HTLV-2, HTLV-3, and HTLV-4.
3. The method of claim 1 , wherein the retrovirus is HIV-1.
4. A method of activating a latent retrovirus in a subject, the method comprising the step of administering to the subject an effective amount of a compound represented by a formula selected from:
wherein R 1 is selected from H, C1-C4 alkyl, C1-C6 aryl, C(O)Ar, C(O)N(CH 3 ) 2 , SO 2 N(CH 3 ) 2 , fluorenylmethyloxycarbonyl, N-((dimethylamino)methylene)-N-methylmethanaminium tetrafluoroborate, N-((dimethylamino)methylene)-N-methylmethanaminium hexafluorophosphate (V), tri(pyrrolidin-1-yl)phosphonium hexafluorophosphate (V), tris(dimethylamino)phosphonium hexafluorophosphate (V), 1-(pyrrolidine-1-ylmethylene)pyrrolidin-1-ium hexafluorophosphate (V), and 1-(piperidin-1-ylmethylene)piperidin-1-ium hexafluorophosphate (V);
wherein each of R 4 , R 5 , and R 6 is independently selected from H, Cl, CH 3 , and NO 2 ,
wherein each of R 7 , R 8 , and R 9 is independently selected from H, Cl, CH 3 , and NO 2 .
5. The method of claim 4 , wherein the retrovirus is selected from HIV-1, HIV-2, SIV, XMRV, HTLV-1, HTLV-2, HTLV-3, and HTLV-4.
6. The method of claim 4 , wherein the retrovirus is HIV-1.
7. The method of claim 4 , wherein R 1 is selected from H and N-((dimethylamino)methylene) -N-methylmethanaminium hexafluorophosphate (V).
8. The method of claim 4 , wherein R 1 is H.
9. The method of claim 4 , wherein the compound is represented by a formula:
10. The method of claim 4 , wherein the compound is represented by a formula:
11. The method of claim 4 , wherein the compound is represented by a formula:
12. The method of claim 4 , wherein the compound is represented by a formula:
13. A method of activating a latent retrovirus in a subject, the method comprising the step of administering to the subject an effective amount of a compound selected from:
14. The method of claim 13 , wherein the retrovirus is selected from HIV-1, HIV-2, SIV, XMRV, HTLV-1, HTLV-2, HTLV-3, and HTLV-4.
15. The method of claim 13 , wherein the retrovirus is HIV-1.
16. The method of claim 13 , wherein the compound is selected from:
17. The method of claim 16 , wherein the retrovirus is selected from HIV-1, HIV-2, SIV, XMRV, HTLV-1, HTLV-2, HTLV-3, and HTLV-4.
18. The method of claim 16 , wherein the retrovirus is HIV-1.
19. The method of claim 13 , wherein the subject is a population of cells.
20. The method of claim 13 , wherein the subject is a mammal.