4-oxoquinoline derivatives
View Patent ↗This invention relates to novel compounds that are 4-oxoquinoline derivatives and pharmaceutically acceptable salts thereof. More specifically, this invention relates to novel 4-oxoquinoline derivatives that are derivatives of elvitegravir. This invention also provides pyrogen-free compositions comprising one or more compounds of this invention and a carrier, and the use of the disclosed compounds and compositions in methods of treating diseases and conditions that are beneficially treated by administering an HIV integrase inhibitor, such as elvitegravir.
1. A compound of Formula I:
wherein:
each Y is independently selected from hydrogen and deuterium;
R 1 is selected from CH 3 , CH 2 D, CHD 2 and CD 3 ;
R 2 is an isopropyl group optionally containing 1 to 7 deuterium atoms; and
when each Y is hydrogen, at least one R contains a deuterium atom,
wherein the compound is compound 107 set forth in the table below:
Compound
R 1
R 2
Y 1a
Y 1b
Y 2a
Y 2b
Y 3
107
CH 3
(CD 3 ) 2 CD—
H
H
D
D
D
or a pharmaceutically acceptable salt thereof, wherein any atom not designated as deuterium is present at its natural isotopic abundance.
2. A pyrogen-free pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
3. The composition of claim 2 further comprising a second therapeutic agent useful in the treatment of HIV infection.
4. The composition of claim 3 , wherein the second therapeutic agent is selected from the group consisting of: ritonavir; darunavir; tipranavir; and any combination thereof.
5. A method of inhibiting the activity of HIV integrase in a cell infected with an HIV virus, comprising contacting the cell with a compound of claim 1 or a pharmaceutically acceptable salt thereof.
6. 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 or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , further comprising co-administering to the patient in need thereof a second therapeutic agent useful in the treatment of HIV infection.
8. The method of claim 7 , wherein the second therapeutic agent is selected from the group consisting of: ritonavir; darunavir; tipranavir; and any combination thereof.