Azapeptide derivatives
This invention relates to novel compounds that are azapeptides, and pharmaceutically acceptable salts thereof. More specifically, the invention relates to novel azapeptide compounds that are derivatives of the HIV protease inhibitor atazanavir sulfate. This invention also provides pyrogen-free compositions comprising one or more compounds of the invention and a carrier, and the use of the disclosed compounds and compositions in methods of treating diseases and conditions that are treated by administering HIV protease inhibitors. The invention also relates to the use of one or more of the disclosed compounds as reagents in analytical studies involving atazanavir.
1. A compound of the following formula
or a pharmaceutically acceptable salt thereof, wherein any atom not designated as deuterium is present at its natural isotopic abundance.
2. A pharmaceutical composition comprising the compound claim 1 and a pharmaceutically acceptable carrier.
3. The composition of claim 2 , additionally comprising a second therapeutic agent selected from a second HIV protease inhibitor, a non-nucleoside reverse transcriptase inhibitor, a nucleoside/nucleotide reverse transcriptase inhibitor, a viral entry inhibitor, an integrase inhibitor, an immune based antiretroviral agent, a viral maturation inhibitor, a cellular inhibitor, or combinations of two or more of the above.
4. The composition of claim 3 , wherein the second therapeutic agent is selected from ritonavir, efavirenz, didanosine, tenofovir disoproxil, nelfinavir mesilate, aniprenavir, raltegravir potassium, saquinavir, lopinavir, nevirapine, emtricitabine, abacavir, lamivudine, zidovudine, maraviroc, stavudine, darunavir, fosamprenavir, vicriviroc, a pharmaceutically acceptable salt of any of the foregoing, and combinations thereof.
5. The composition of claim 4 , wherein the second therapeutic agent is selected from ritonavir, efavirenz, didanosine, raltegravir potassium, tenofovir disoproxil, lamivudine, abacavir, zidovudine, emtricitabine, a pharmaceutically acceptable salt of any of the foregoing, and combinations thereof.
6. The composition of claim 5 , comprising two to three additional second therapeutic agents independently selected from ritonavir, efavirenz, didanosine, raltegravir potassium, tenofovir disoproxil, lamivudine, abacavir, zidovudine, emtricitabine, and a pharmaceutically acceptable salt of any of the foregoing.
7. The composition of claim 6 , comprising two additional second agents independently selected from ritonavir, efavirenz, didanosine, raltegravir potassium, tenofovir disoproxil, lamivudine, abacavir, zidovudine, emtricitabine, and a pharmaceutically acceptable salt of any of the foregoing.
8. A method of treating HIV infection in a patient in need thereof comprising the step of administering to the patient an effective amount of a compound of claim 1 .
9. The method of claim 8 , further comprising administering to the patient a second therapeutic agent selected from a second HIV protease inhibitor, a non-nucleoside reverse transcriptase inhibitor, a nucleoside/nucleotide reverse transcriptase inhibitor, a viral entry inhibitor, an integrase inhibitor, an immune based antiretroviral agent, a viral maturation inhibitor, a cellular inhibitor, or combinations of two or more of the above.
10. The method of claim 9 , wherein the second therapeutic agent is selected from ritonavir, efavirenz, didanosine, tenofovir disoproxil, nelfinavir mesilate, amprenavir, raltegravir potassium, saquinavir, lopinavir, nevirapine, emtricitabine, abacavir, lamivudine, zidovudine, maraviroc, stavudine, darunavir, fosamprenavir, vicriviroc, a pharmaceutically acceptable salt of any of the foregoing, and combinations thereof.
11. The method of claim 10 , wherein the second therapeutic agent is selected from ritonavir, efavirenz, didanosine, raltegravir potassium, tenofovir disoproxil, lamivudine, abacavir, zidovudine, emtricitabine, a pharmaceutically acceptable salt of any of the foregoing, and combinations thereof.
12. The method of claim 11 , further comprising administering to the patient two to three additional second therapeutic agents independently selected from ritonavir, efavirenz, didanosine, raltegravir potassium, tenofovir disoproxil, lamivudine, abacavir, zidovudine, emtricitabine, and a pharmaceutically acceptable salt of any of the foregoing.
13. The method of claim 12 , further comprising administering to the patient two additional second agents independently selected from ritonavir, efavirenz, didanosine, raltegravir potassium, tenofovir disoproxil, lamivudine, abacavir, zidovudine, emtricitabine, and a pharmaceutically acceptable salt of any of the foregoing.