IRE-1α inhibitors
AssigneeMannKind Corporation
InventorsJohn B. Patterson, David G. Lonergan, Gary A. Flynn, Qingping Zeng, Peter V. Pallai
Life of this patent
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Abstract
Compounds which directly inhibit IRE-1α activity in vitro, prodrugs, and pharmaceutically acceptable salts thereof. Such compounds and prodrugs are useful for treating diseases associated with the unfolded protein response and can be used as single agents or in combination therapies.
Claims24
A compound which directly inhibits IRE-1α activity in vitro and is represented by structural formula (B):
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is hydrogen, phenyl or an optionally benzofused five- or six-membered heterocycle, wherein the phenyl or the optionally benzofused five- or six-membered heterocycle is optionally substituted with
- —CH3OH, —CHO, —OCH3, halogen, —OH, —CH3,
- R2 is phenyl or an optionally benzofused five- or six-membered heterocycle, wherein the phenyl or the optionally benzofused five- or six-membered heterocycle is optionally substituted with
- —CH3OH, —CHO, —OCH3, halogen, —OH, —CH3,
- R3 is hydrogen, halogen, —NO2, C1-C3 linear or branched alkyl, C1-C3 linear or branched alkoxy, C1-C3 linear or branched hydroxyl alkyl,
- and
- R4 is hydrogen,
The method of claim 3 wherein the compound is the compound of claim 21.
The method of claim 3 wherein the compound is the compound of claim 22.
A compound which has the structural formula:
A pharmaceutical composition comprising:
- a compound which has the structural formula
- or a pharmaceutically acceptable salt thereof;
- and
- a pharmaceutically acceptable vehicle.
A method of inhibiting the activity of IRE1-α comprising contacting the IRE1-α enzyme with a compound having the structural formula
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.