(+)-MORPHINANS AS ANTAGONISTS OF TOLL-LIKE RECEPTOR 9 AND THERAPEUTIC USES THEREOF

摘要

The present invention provides (+)-morphinans comprising Toll-like receptor 9 (TLR9) antagonist activity, as well as methods for using the (+)-morphinans to treat a variety of disorders.

主权项

1. A method for treating a hepatic disorder in a subject in need thereof, the method comprising administering to the subject a compound of Formula (IIa) or a pharmaceutically acceptable salt thereof: wherein:
R is hydrogen, alkyl, alkenyl, allyl, cycloalkylmethyl, alkylaryl, acyl, acylalkyl, acylcycloalkyl, acylaryl, acyloxy, acyloxyalkyl, acyloxyaryl, alkoxy, or alkoxyalkyl;R1 is hydrogen, halo, hydroxy, alkoxy, alkoxyalkyl, alkoxyalkenyl, aryloxy, alkyl, alkenyl, aryl, heteroaryl, or amine;R3 is hydroxy, alkoxy, aryloxy, acyl, acyloxy, or protected hydroxy;A1 is hydrogen, hydroxy, keto, alkoxy, acyl, acyloxy, amino, amide, alkylamine, hydroxyalkylamine, carboxylalkylamine, alkylcarboxylalkylamine, arylamine, alkyl, alkenyl, aryl, substituted alkyl, substituted alkenyl, or substituted aryl;Y is hydrogen, hydroxy, alkoxy, or protected hydroxy; andthe dashed line represents an optional double bond.