Compounds for the treatment of inflammatory disorders
View Patent ↗This invention relates to compounds of the Formula (I): or a pharmaceutically acceptable salt, solvate or isomer thereof, wherein n, M, V, T, W, X, U, R 1 and R 2 are as disclosed in the present specification, and which compounds are useful for the treatment of diseases or conditions mediated by MMPs, TNF-α or combinations thereof.
1. A compound represented by the structural formula (III):
or a pharmaceutically acceptable salt of said compound, wherein:
L is aryl or heteroaryl;
R 1 is
T is H;
G 2 is H,
V is selected from the group consisting of —C(O)OH and —C(O)N(H)OH;
x is 0 to 2;
each of R 2 , R 4 and R 5 is the same or different and each is independently selected from the group consisting of H, halo, alkyl, R 22 -substituted alkyl, cycloalkyl, heterocyclyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, —OR 6 , —C(O)R 7 , —C(O)OR 6 , —NR 24 R 25 , —NR 24 C(O)R 25 , —N(═C—O—NR 24 R 25 ), —NR 24 S(O) 2 R 25 , wherein each of the cycloalkyl, heterocyclyl, arylalkyl, heteroarylalkyl, aryl and heteroaryl groups of R 2 , R 4 and R 5 is unsubstituted or optionally independently substituted with one to six alkyl, R 22 -substituted alkyl or R 22 moieties which can be the same or different, each R 22 moiety being independently selected from the group of R 22 moieties below;
each R 3 is the same or different and is independently selected from the group consisting of H, alkyl, R 22 -substituted alkyl, heterocyclyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, —OR 6 , —C(O)R 7 , —C(O)OR 6 , —NR 24 R 25 , —NR 24 C(O)R 25 , —N(═C—O—NR 24 R 25 ) and —NR 24 S(O) 2 R 25 , wherein each of the cycloalkyl, heterocyclyl, arylalkyl, heteroarylalkyl, aryl and heteroaryl groups of R 3 is unsubstituted or optionally independently substituted with one to four alkyl, R 22 -substituted alkyl or R 22 moieties which can be the same or different, each R 22 moiety being independently selected from the group of R 22 moieties below;
each R 6 is independently selected from the group consisting of H, alkyl and —OCF 3 ;
each R 7 is independently selected from the group consisting of H, alkyl, heteroaryl and —CF 3 ;
each R 22 is independently selected from the group consisting of:
halo, alkynyl, aryl, heteroaryl, —OR 24 , —(C 1 -C 6 alkyl)-OR 24 , —CN, —NO 2 , —NR 24 R 25 , —C(O)R 23 , —C(O)OR 23 , —C(O)NR 24 R 25 , —S(O) X NR 24 R 25 , —S(O) X R 23 , —CF 3 , —OCF 3 , —CF 2 CF 3 , —C(═NOH)R 23 , —N(R 24 )S(O) x R 25 , —N(R 24 )C(O)R 25 , and —N(R 24 )C(O)NR 24 R 25 ,
or two R 22 groups taken together with the carbon to which both R 22 groups are attached is
each R 23 is independently selected from the group consisting of H, hydroxyl, halo and alkyl;
each R 24 is independently selected from the group consisting of H and alkyl; and
each R 25 is independently selected from the group consisting of H, hydroxyl, alkyl, hydroxyalkyl, aryl, cycloalkyl, heteroaryl, —NR 24 R 24 , —(C 1 to C 6 alkyl)NR 24 N 24 , —CF 3 and —S(O) x R 23 .
2. The compound according to claim 1 , wherein R 2 and R 5 are both hydrogen.
3. The compound according to claim 1 , wherein one of R 3 and R 4 is H, and the other is —C(O)OR 6 .
4. The compound according to claim 1 , wherein both R 3 and R 4 are H.
5. The compound according to claim 1 , wherein L is aryl.
6. The compound according to claim 5 , wherein said aryl is phenyl.
7. A compound according to claim 1 , selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
8. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound according to claim 1 , or a pharmaceutically acceptable salt thereof, in combination with at least one pharmaceutically acceptable carrier.
9. The pharmaceutical composition of claim 8 , additionally comprising an anti-inflammatory agent.