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US 2023/0399303 A1Published application
Macrophage Migration Inhibitory Factor Inhibitors, and Methods of Making and Using Same
OwnerWilliam L. Jorgenseninventor
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Abstract
The present disclosure provides inhibitors of MIF tautomerase activity. In certain embodiments, the compounds inhibitors are useful in treating or preventing inflammatory and/or auto-immune diseases. In other embodiments, the compounds are useful in reversing, ameliorating, and/or preventing tumor growth. In yet other embodiments, the compounds are useful in reversing, ameliorating, and/or preventing angiogenesis.
Claims20
A compound of formula (I), or a salt, enantiomer, tautomer, or solvate thereof:
- wherein:
- R1 and R1′ are each independently H, C1-3 alkyl, or halogen;
- X is CH2, O, or S;
- A is a fused 5-membered heteroaryl ring or a fused 6-membered aryl or heteroaryl ring;
- each G is independently selected from the group consisting of halogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocyclyl, C3-10 cycloalkyl-C1-10 alkyl, C3-10 cycloalkyl-C1-10 heteroalkyl, C6-10 aryl-C1-10 alkyl, C6-10 aryl-C1-10 heteroalkyl, 5-10 membered heteroaryl-C1-10 alkyl, 5-10 membered heteroaryl-C1-10 heteroalkyl, 4-10 membered heterocyclyl-C1-10 alkyl, 4-10 membered heterocyclyl-C1-10 heteroalkyl, CN, NO2, OR, SR, C(O)R, C(O)NRR′, C(O)OR, OC(O)R, OC(O)NRR′, NRR′, NRC(O)R, NRC(O)NRR′, NRC(O)OR, C(═NR)NRR′, NRC(═NR)NRR′, S(O)R, S(O)2R, NRS(O)2R, S(O)2NRR′, and combinations thereof;
- Ar is a 5-membered heteroaryl or a 6-membered aryl or heteroaryl ring;
- each Z is a substituent on Ar independently selected from the group consisting of halogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocyclyl, C3-10 cycloalkyl-C1-10 alkyl, C3-10 cycloalkyl-C1-10 heteroalkyl, C6-10 aryl-C1-10 alkyl, C6-10 aryl-C1-10 heteroalkyl, 5-10 membered heteroaryl-C1-10 alkyl, 5-10 membered heteroaryl-C1-10 heteroalkyl, 4-10 membered heterocyclyl-C1-10 alkyl, 4-10 membered heterocyclyl-C1-10 heteroalkyl, CN, NO2, OR, SR, C(O)R, C(O)NRR′, C(O)OR, OC(O)R, OC(O)NRR′, NRR′, NRC(O)R, NRC(O)NRR′, NRC(O)OR, C(═NR)NRR′, NRC(═NR)NRR′, S(O)R, S(O)2R, NRS(O)2R, S(O)2NRR′, —(OCH2CH2)p-4-10 membered heterocyclyl, —O(CH2CH2O)p-4-10 membered heterocyclyl, —(OCH2CH2)p-4-10 membered heteroaryl, —O(CH2CH2O)p-4-10 membered heteroaryl, —O(CH2CH2O)p—C1-4 alkyl, and combinations thereof;
- each R and R′ is independently H or C1-10 hydrocarbyl;
- n is an integer from 1 to 4;
- m is an integer from 1 to 5;
- and
- p is an integer from 1 to 5;
- with the proviso that if
- Ar is phenyl;
- A is a fused 6-membered aryl ring having the structure
- substituted at the position marked with * by hydrogen, hydroxy, Ci-s alkoxy, Ci-s haloalkyl, or C1-5 haloalkoxy;
- and
- m is 1;
- then Z is not OH, C1-5 alkyl, C1-5 alkoxy, C1-5 haloalkyl, C1-5 haloalkoxy, OCF3, phenyl, or halogen.
16 more elements
3-8. (canceled)
22-24. (canceled)
(canceled)
Dependencies are inferred from the claim text.