Inhibitors of macrophage migration inhibitory factor and methods for identifying the same
AssigneeAvanir Pharmaceuticals
InventorsJagadish Sircar, Sunil KC, Wenbin Ying
Life of this patent
Estimating the term…
Abstract
Inhibitors of MIF are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with MIF activity. The inhibitors of MIF have the following structures: including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein n, R1, R2, R3, R4, X, and Z are as defined herein. Compositions containing an inhibitor of MIF in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.
Claims36
A compound having a structure selected from the group consisting of:
- or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:
- X is oxygen or sulfur;
- Z is —CH2— or —C(═O)—;
- R1 is selected from the group consisting of C1-10 alkyl, aryl C1-10 alkyl, aryl, 5- to 7-membered monocyclic heterocyclic ring, and 7- to 14-membered polycyclic heterocyclic ring, wherein R1 is unsubstituted or substituted with at least one substitutent selected from the group consisting of halogen, alkyl, alkoxy, hydroxy, amino, alkylamino, dialkylamino, and keto;
- R2 and R3 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, hydroxy, amino, alkylamino, dialkylamino, and keto;
- R4 is selected from the group consisting of —CH2R7, —C(═O)NR5R6, and —C(═O)R7;
- R5 and R6 are independently selected from the group consisting of C1-10 alkyl, aryl, aryl C1-10 alkyl, 5- to 7-membered monocyclic heterocyclic ring, and 7- to 14-membered polycyclic heterocyclic ring, wherein R5 and R6 are independently unsubstituted or substituted with at least one substitutent selected from the group consisting of halogen, alkoxy, hydroxy, amino, alkylamino, dialkylamino, and keto, or R5 and R6 taken together with a nitrogen atom to which they are attached form a 5- to 7-membered monocyclic heterocyclic ring or a 7- to 14-membered polycyclic heterocyclic ring, wherein the ring is unsubstituted or substituted with at least one substitutent selected from the group consisting of halogen, alkyl, alkoxy, hydroxy, amino, alkylamino, dialkylamino, and keto;
- R7 is selected from the group consisting of C1-10 alkyl, aryl, aryl C1-10 alkyl, 5- to 7-membered monocyclic heterocyclic ring, and 7- to 14-membered polycyclic heterocyclic ring, wherein R7 is unsubstituted or substituted with at least one substitutent selected from the group consisting of halogen, alkyl, alkoxy, amino, alkylamino, dialkylamino, and keto;
- and
- n is 0, 1 or 2, with the proviso that when n is 0, Z is —C(═O)—.
A compound having a structure selected from the group consisting of:
- or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:
- X is oxygen or sulfur;
- Z is —CH2— or —C(═O)—;
- R1 is selected from the group consisting of C1-10 alkyl, aryl C1-10 alkyl, aryl, 5- to 7-membered monocyclic heterocyclic ring, and 7- to 14-membered polycyclic heterocyclic ring, wherein R1 is unsubstituted or substituted with at least one substitutent selected from the group consisting of halogen, alkyl, alkoxy, hydroxy, amino, alkylamino, dialkylamino, and keto;
- R2 and R3 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, hydroxy, amino, alkylamino, dialkylamino, and keto;
- R4 is selected from the group consisting of hydrogen, methyl, and methyl substituted by keto;
- and
- n is 0, 1 or 2, with the proviso that when n is 0, Z is —C(═O)—.
Dependencies are inferred from the claim text.