Compounds for inflammation and immune-related uses
The invention relates to compounds of structural formula (I) and structural formula (VI): or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein R, R 1 , R 2 , Z, L, and n are defined herein. Those compounds are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.
1. A compound represented by structural formula (V′):
or a pharmaceutically acceptable salt thereof, wherein:
R 12 is phenyl optionally substituted with one or more substituents selected from the group consisting of alkyl, haloalkyl, heteroaryl, a halo, cyano, —OR 17 , —C(X 3 )OR 17 , and —C(X 3 )NR 15 R 16 ;
R 13 is pyridinyl, which is optionally substituted with one or more substituents selected from the group consisting of a lower alkyl, a halo, cyano, a lower haloalkyl, and a lower alkoxy;
R 14 is H;
R 15 and R 16 , for each occurrence are, independently, H, alkyl, or R 15 and R 16 are taken together with the nitrogen to which they are attached to form heterocyclyl or heteroaryl;
R 17 is H, alkyl or cycloalkyl; and
X 3 is ═O.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said R 12 is phenyl, optionally substituted with one or more substituents selected from the group consisting of —CH 3 , —CF 3 , chloro, cyano, monocyclic 5-membered heteroaryl comprising 1 or 2 heteroatoms selected from O and N, —OR 17 , —C(O)OR 17 , and —C(O)NH 2 ; wherein said monocyclic 5-membered heteroaryl is furyl, pyrrolyl, oxazolyl, imidazolyl, thiazolyl, isoxazolyl, pyrazolyl, or isothiazolyl.
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said R 12 is phenyl, optionally substituted with one or more substituents selected from the group consisting of —CH 3 , —CH 2 CH 3 , —CF 3 , chloro, cyano, —OR 17 , —C(O)OMe, —C(O)OEt, —C(O)OPr, —C(O)NH 2 ; furyl, thienyl, pyrrolyl, oxazolyl, imidazolyl, thiazolyl, isoxazolyl, pyrazolyl, or isothiazolyl.
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said R 13 is pyridinyl, which is optionally substituted with one or more substituents selected from the group consisting of an alkyl of 1 to 4 carbon atoms and a fluoro atom.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said R 13 is pyridinyl, which is optionally substituted with one or more substituents selected from the group consisting of methyl and fluoro atom.
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said R 17 is methyl, ethyl, n-propyl, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.
7. A compound represented by structural formula (V′):
or a pharmaceutically acceptable salt thereof, wherein:
R 12 is phenyl optionally substituted with one or more substituents selected from the group consisting of alkyl of 1 to 4 carbon atoms, haloalkyl of 1 to 4 carbon atoms, monocyclic 5- or 6-membered heteroaryl comprising 1 or 2 heteroatoms selected from O and N, cyano, a halo selected from fluoro and chloro, —OR 17 , —C(X 3 )OR 17 , and —C(X 3 )NR 15 R 16 ;
R 13 is pyridinyl, which is optionally substituted with one or more substituents selected from the group consisting of an alkyl of 1 to 4 carbon atoms and a fluoro atom;
R 14 is H;
R 15 and R 16 are H;
R 17 is H, an alkyl of 1 to 4 carbon atoms or cycloalkyl; and
X 3 is ═O.
8. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein
R 12 is phenyl, optionally substituted with one or more substituents selected from the group consisting of —CH 3 , —CF 3 , chloro, cyano, monocyclic 5-membered heteroaryl comprising 1 or 2 heteroatoms selected from O and N, —OR 17 , —C(O)OR 17 , and —C(O)NH 2 ;
R 13 is pyridinyl, which is optionally substituted with one or more substituents selected from the group consisting of an alkyl of 1 to 4 carbon atoms and a fluoro atom;
R 14 is H; and
R 17 is alkyl of 1 to 4 carbon atoms or cycloalkyl.
9. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein said
R 17 is phenyl, optionally substituted with one or more substituents selected from the group consisting of —CH 3 , —CF 3 , chloro, cyano, monocyclic 5-membered heteroaryl comprising 1 or 2 heteroatoms selected from O and N, —OR 17 , —C(O)OR 17 , and —C(O)NH 2 ; wherein said monocyclic 5-membered heteroaryl is furyl, pyrrolyl, oxazolyl, imidazolyl, thiazolyl, isoxazolyl, pyrazolyl, or isothiazolyl,
R 13 is pyridinyl, which is optionally substituted with one or more substituents selected from the group consisting of an alkyl of 1 to 4 carbon atoms and a fluoro atom;
R 14 is H; and
R 17 is an alkyl of 1 to 4 carbon atoms or cycloalkyl.
10. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein said
R 12 is phenyl, optionally substituted with one or more substituents selected from the group consisting of —CH 3 , —CH 2 CH 3 , —CF 3 , chloro, cyano, —OR 17 , —C(O)OMe, —C(O)OEt, —C(O)OPr, —C(O)NH 2 ; furyl, pyrrolyl, oxazolyl, imidazolyl, thiazolyl, isoxazolyl, pyrazolyl, or isothiazolyl;
R 13 is pyridinyl, which is optionally substituted with one or more substituents selected from the group consisting of methyl and fluoro atom;
R 14 is H; and
R 17 is an alkyl of 1 to 4 carbon atoms or cycloalkyl.
11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.