Sulfonamide derivatives and methods of use thereof for improving the pharmacokinetics of a drug

1. A compound having the formula (I):

or a pharmaceutically acceptable salt thereof,

wherein:

A is a 5 or 6-membered heteroarylene group;

W is N or —CH—;

X is N or —C(R 3 )—;

R 1 is selected from —(C 1 -C 6 alkylene)-aryl, —(C 1 -C 6 alkylene)-(5 or 6-membered heteroaryl), —(C 1 -C 6 alkylene)-O-aryl, —(C 1 -C 6 alkylene)-O-(5 or 6-membered heteroaryl) and C 3 -C 6 cycloalkyl, wherein any aryl, heteroaryl or C 3 -C 6 cycloalkyl group can be optionally substituted with up to four R 7 groups, which can be the same or different, and wherein said C 3 -C 6 cycloalkyl group can be fused to a benzene ring and said fused benzene ring can be optionally substituted with up to four R 7 groups, which can be the same or different;

each occurrence of R 2 is independently selected from H, C 1 -C 6 alkyl, —OH, —O—(C 1 -C 6 alkyl) and —(C 1 -C 6 alkylene)-O—(C 1 -C 6 alkyl);

R 3 is selected from H, C 1 -C 6 alkyl, C 1 -C 6 hydroxyalkyl and —CN, or R 3 and an R 2 group, together with the carbon atoms to which they are attached, can combine to form a cyclopropyl ring;

R 4 is H, or R 4 and an R 2 group, can join to form a group selected from —CH 2 —CH 2 —CH 2 —, —C(O)—O—CH 2 —, —CH 2 —O—CH 2 — and —CH 2 —N(R 8 )—CH 2 —;

R 5 is —NH(R 6 ), 5 or 6-membered monocyclic heterocycloalkyl or 9 or 10-membered bicyclic heterocycloalkyl, wherein said 5 or 6-membered monocyclic heterocycloalkyl group can optionally form a spirocycle with a C 3 -C 6 cycloalkyl group or another 5 or 6-membered monocyclic heterocycloalkyl group, and wherein said 5 or 6-membered monocyclic heterocycloalkyl group and said 9 or 10-membered bicyclic heterocycloalkyl group can be optionally substituted on one or more ring carbon atoms with up to four R 7 groups, which can be the same or different, and wherein a ring carbon atom of a 5 or 6-membered monocyclic heterocycloalkyl group may be functionalized as a carbonyl group

R 6 is C 1 -C 6 alkyl or 5 or 6-membered heteroaryl, wherein said C 1 -C 6 alkyl group is optionally substituted with 1 or 2 groups, each independently being NH 2 or halo, and wherein said 5 or 6-membered heteroaryl group can be optionally substituted with up to four R 7 groups;

each occurrence of R 7 is independently selected from C 1 -C 6 alkyl, 5 or 6-membered heterocycloalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 haloalkyl, halo, —CN, —N(R 8 ) 2 , —CH 2 N(R 8 ) 2 , —OR 8 , —C(O)OR 8 , —SR 8 , —S(O) 2 R 8 and —C(O)N(R 8 ) 2 , wherein said 5 or 6-membered heterocycloalkyl group can be optionally substituted with a group selected from C 1 -C 6 alkyl, halo, C 1 -C 6 hydroxyalkyl, C 1 -C 6 haloalkyl, halo, —CN, —N(R 8 ) 2 and —OR 8 ; and

each occurrence of R 8 is independently H or C 1 -C 6 alkyl.

2. The compound of claim 1 , wherein A is thiazolyl, pyridyl or pyrazinyl.

3. The compound of claim 1 , having the formula (Ia):

or a pharmaceutically acceptable salt thereof,

wherein:

R 5 is 5 or 6-membered monocyclic heterocycloalkyl, 9 or 10-membered bicyclic heterocycloalkyl, wherein said 5 or 6-membered monocyclic heterocycloalkyl group can optionally form a spirocycle with a C 3 -C 6 cycloalkyl group or another 5 or 6-membered monocyclic heterocycloalkyl group, and wherein said 5 or 6-membered monocyclic heterocycloalkyl group, said 9 or 10-membered bicyclic heterocycloalkyl and said spirocycle can be optionally substituted on one ring carbon atom with C 1 -C 6 alkyl or halo; and

each occurrence of R 7 is independently selected from H, C 1 -C 6 alkyl or halo.

4. The compound of claim 1 , wherein R 5 is 5 or 6-membered monocyclic heterocycloalkyl, which can optionally form a spirocycle and/or be optionally substituted as described in claim 1 .

5. The compound of claim 1 , wherein R 5 is 9 or 10-membered bicyclic heterocycloalkyl, which can be optionally substituted as described in claim 1 .

6. The compound of claim 1 , wherein R 5 is selected from:

7. The compound of claim 3 , wherein R 7 is halo.

8. The compound of claim 7 , wherein R 7 is F.

9. The compound of claim 1 , having the structure:

or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising an effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

11. The pharmaceutical composition of claim 10 , further comprising an anti-HIV drug.

12. The pharmaceutical composition of claim 11 , wherein said anti-HIV drug is selected from an HIV protease inhibitor, an HIV integrase inhibitor, a nucleoside reverse transcriptase inhibitor and a non-nucleoside reverse-transcriptase inhibitor.

13. The pharmaceutical composition of claim 12 , wherein said anti-HIV drug is selected from raltegravir, lamivudine, abacavir, darunavir, ritonavir, dolutegravir, atazanavir, elvitegravir and lopinavir.

14. The pharmaceutical composition of claim 13 , further comprising a second anti-HIV drug, which is selected from an HIV protease inhibitor, an HIV integrase inhibitor, a nucleoside reverse transcriptase inhibitor and a non-nucleoside reverse-transcriptase inhibitor.

15. A method for improving the pharmacokinetics of a therapeutic compound that is metabolized by a CYP3A enzyme in subject, said method comprising administering to said subject in need of such treatment a combination of: (a) said therapeutic compound that is metabolized by a CYP3A enzyme and (b) a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

16. The method of claim 15 , wherein said therapeutic compound is an anti-HIV drug.

17. The method of claim 16 , wherein said anti-HIV drug is selected from an HIV protease inhibitor, an HIV integrase inhibitor, a nucleoside reverse transcriptase inhibitor and a non-nucleoside reverse-transcriptase inhibitor.

18. The method of claim 17 , wherein said anti-HIV drug is selected from raltegravir, lamivudine, abacavir, ritonavir, dolutegravir, atazanavir, darunavir, elvitegravir and lopinavir.

19. The method of claim 18 , wherein said anti-HIV drug is raltegravir.

20. The method of claim 15 , wherein the therapeutic compound of (a) is metabolized by CYP3A4.