Tetrahydro-isohumulone derivatives, methods of making and using

A method of inhibiting inflammation or treating a condition associated with inflammation in a subject in need thereof comprising administering a therapeutically effective amount of a tetrahydro-iso-alpha acid (THIAA) derivative selected from the group consisting of (4R,5R)-3,4-dihydroxy-4-(1-hydroxy-4-methylpentyl)-2-(N-methoxy-3-methylbutanimidoyl)-5-(3-methylbutyl)cyclopent-2-en-1-one (KDT0005), (4R,5R)-4-hydroxy-2-{1-[(2-hydroxyethyl)amino]-3-methylbutyl idene}-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopentane-1,3-dione (KDT0017), (4R,5R)-4-hydroxy-5-(3-methylbutyl)-2-[3-methyl-1-(methylamino)butylidene]-4-(4-methylpentanoyl)cyclopentane-1,3-dione (KDT0020), (4R,5R)-2-[1-(benzylamino)-3-methyl butyl idene]-4-hydroxy-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopentane-1,3-dione (KDT0024), (1 S,5R)-2-hydroxy-3-(3-methylbutanoyl)-5-(3-methylbutyl)-1-(4-methylpentanoyl)-4-oxocyclopent-2-en-1-yl 2,2-dimethylpropanoate (KDT0033), (1 S, 5R)-2-hydroxy-3-(3-methylbutanoyl)-5-(3-methylbutyl)-1-(4-methylpentanoyl)-4-oxocyclopent-2-en-1-yl 3,3-dimethylbutanoate (KDT0034), but-3-yn-1-yl (1S,5R)-2-hydroxy-3-(3-methylbutanoyl)-5-(3-methylbutyl)-1-(4-methylpentanoyl)-4-oxocyclopent-2-en-1-yl carbonate (KDT0035), (1 S, 5R)-2-hydroxy-5-(3-methylbutyl)-1-(4-methylpentanoyl)-3-(2-methylpropanoyl)-4-oxocyclopent-2-en-1-yl decanoate (KDT0036), (1 S,5R)-2-hydroxy-5-(3-methylbutyl)-1-(4-methylpentanoyl)-3-(2-methylpropanoyl)-4-oxocyclopent-2-en-1-yl 2-methylpropyl carbonate (KDT0037), 5-[(1 S,5R)-1,2-dihydroxy-3-(3-methylbutanoyl)-5-(3-methylbutyl)-4-oxocyclopent-2-en-1-yl]-2-methyl-5-oxopentanoic acid (KDT0038), (4R,5R)-3,4-dihydroxy-4-(1-hydroxy-4-methylpentyl)-2-(3-methylbutanoyl)-5-(3-methylbutyl)cyclopent-2-en-1-one (KDT0039), (4S,5R)-3,4-dihydroxy-4-[(2E)-4-hydroxy-4-methylpent-2-enoyl]-2-(3-methylbutanoyl)-5-(3-methylbut-2-en-1-yl)cyclopent-2-en-1-one (KDT0040), (4R,5R)-3,4-dihydroxy-2-(N-methoxy-3-methylbutanimidoyl)-4-(N-methoxy-4-methylpentanimidoyl)-5-(3-methylbutyl)cyclopent-2-en-1-one (KDT0001/2), (1 S,5R)-2-hydroxy-5-(3-methylbutyl)-1-(4-methylpentanoyl)-3-(2-methylpropanoyl)-4-oxocyclopent-2-en-1-yl 3,3-dimethylbutanoate (KDT0041), and (1 S,5R)-2-hydroxy-5-(3-methylbutyl)-1-(4-methylpentanoyl)-3-(2-methylpropanoyl)-4-oxocyclopent-2-en-1-yl benzoate (KDT0042), (1R,2S)-3-hydroxy-4-(3-methylbutanoyl)-2-(3-methylbutyl)-1-(4-methylpentanoyl)-5-oxocyclopent-3-en-1-yl 2-[4-(2-methylpropyl)phenyl]propanoate (KDT0043), or a salt or crystal thereof, or a substantially enantiomerically pure composition thereof.