Tiglien-3-one derivatives

A method of stimulating a localised inflammatory response comprising administering to a subject in need thereof a compound of formula (II) or a pharmaceutically acceptable salt thereof, wherein the compound of formula (II) has the following structure:

• wherein:
• X is —O—;
• R1 and R2 are independently selected from hydrogen, OH, OC1-C10 alkyl, OC2-C10alkenyl, OC2-C10alkynyl, Ocycloalkyl, OC(O)C1-C10alkyl, OC(O)C2-C10 alkenyl, OC(O)C2-C10alkynyl, OC(O)cycloalkyl, OC(O)NHC1-C10 alkyl, OC(O)NHC2-C10alkenyl, OC(O)NHC2-C10alkynyl, OC(O)NHcycloalkyl, OC(O)NHaryl, OC(S)NHC1-C10alkyl, OC(S)NHC2-C10alkenyl, OC(S)NHC2-C10 alkynyl, OC(S)NHcycloalkyl and OC(S)NHaryl, or R1 and R2 taken together are ═O, ═S, ═NH or ═N(C1-C6 alkyl);
• R3 is hydrogen, —C1-C10alkyl, —C2-C10alkenyl or —C2-C10alkynyl;
• R4 and R5 are each hydrogen, —C1-C10alkyl, —C2-C10alkenyl, —C2-C10 alkynyl, —OH, —OC1-C10alkyl, —OC2-C10alkenyl, —OC2-C10alkynyl, —Ocycloalkyl, —OC(O)C1-C10 alkyl, —OC(O)C2-C10alkenyl, —OC(O)C2-C10alkynyl, —OC(O)cycloalkyl, —OC(O)aryl, —OC(O)NHC1-C10alkyl, —OC(O)NHC2-C10alkenyl, —OC(O)NHC2-C10alkynyl, —OC(O)NHcycloalkyl, —OC(O)NHaryl, —OC(S)NHC1-C10alkyl, —OC(S)NHC2-C10 alkenyl, —OC(S)NHC2-C10alkynyl, —OC(S)NHcycloalkyl, —OC(S)NHaryl, F, Cl, Br, I, —CN, —NO2 or N(R25)2, or R4 and R5 taken together form a double bond or are —O—, —S—, —NR25— or —CR26R27—;
• R6 is selected from hydrogen, —C1-C10alkyl, —C2-C10alkenyl and —C2-C10 alkynyl;
• R8 is selected from hydrogen, —C1-C10alkyl, —C2-C10alkenyl and —C2-C10 alkynyl;
• R10 is selected from hydrogen, —C1-C10alkyl, —C2-C10alkenyl and —C2-C10 alkynyl;
• R11 is selected from OH, OC1-C20alkyl, OC2-C20alkenyl, OC2-C20 alkynyl, Ocycloalkyl, OC(O)C1-C20alkyl, OC(O)C2-C20alkenyl, OC(O)C2-C20alkynyl, OC(O)cycloalkyl, OC(O)aryl, OC(O)NHC1-C20alkyl, OC(O)NHC2-C20alkenyl, OC(O)NHC2-C20alkynyl, OC(O)NHcycloalkyl, OC(O)NHaryl, OC(S)NHC1-C20 alkyl, OC(S)NHC2-C20alkenyl, OC(S)NHC2-C20alkynyl, OC(S)NHcycloalkyl and OC(S)NHaryl, or R10 and R11 taken together form a carbonyl group (═O);
• R12 is selected from OH, OC1-C20alkyl, OC2-C20alkenyl, OC2-C20 alkynyl, Ocycloalkyl, OC(O)C1-C20alkyl, OC(O)C2-C20alkenyl, OC(O)C2-C20 alkynyl, OC(O)cycloalkyl, OC(O)aryl, OC(O)NHC1-C20alkyl, OC(O)NHC2-C20alkenyl, OC(O)NHC2-C20alkynyl, OC(O)NHcycloalkyl, OC(O)NHaryl, OC(S)NHC1-C20 alkyl, OC(S)NHC2-C20alkenyl, OC(S)NHC2-C20alkynyl, OC(S)NHcycloalkyl and OC(S)NHaryl;
• R13 and R14 are independently selected from hydrogen and —C1-C10 alkyl;
• R18 is selected from C1-C20alkyl, C2-C20alkenyl, C2-C20alkynyl, OH, OC1-C20alkyl, OC2-C20alkenyl, OC2-C20 alkynyl, Ocycloalkyl, OC(O)C1-C20alkyl, OC(O)C2-C20alkenyl, OC(O)C2-C20 alkynyl, OC(O)cycloalkyl, OC(O)aryl, NHC1-C20alkyl, NHC2-C20alkenyl, NHC2-C20alkynyl, NHcycloalkyl, NHaryl, OC(O)NHC1-C20alkyl, OC(O)NHC2-C20alkenyl, OC(O)NHC2-C20alkynyl, OC(O)NHcycloalkyl, OC(O)NHaryl, OC(S)NHC1-C20alkyl, OC(S)NHC2-C20 alkenyl, OC(S)NHC2-C20alkynyl, OC(S)NHcycloalkyl and OC(S)NHaryl;
• R19 and R20 are independently selected from hydrogen, —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C20alkynyl, —OH, —OC1-C6alkyl, —OC2-C6alkenyl, —OC2-C6 alkynyl, —Ocycloalkyl, —OC(O)C1-C6alkyl, —OC(O)C2-C6alkenyl, —OC(O)C2-C6 alkynyl, —OC(O)cycloalkyl and —OC(O)aryl or R19 and R20 taken together form a carbonyl or thiocarbonyl group;
• R21 is selected from hydrogen, —C1-C10alkyl, —C2-C10alkenyl and —C2-C10 alkynyl;
• R22 is selected from hydrogen, OH, OC1-C20alkyl, OC2-C20alkenyl, OC2-C20alkynyl, Ocycloalkyl, OC(O)C1-C20alkyl, OC(O)C2-C20alkenyl, OC(O)C2-C20 alkynyl, OC(O)cycloalkyl, OC(O)aryl, OC(O)NHC1-C20alkyl, OC(O)NHC2-C20alkenyl, OC(O)NHC2-C20alkynyl, OC(O)NHcycloalkyl, OC(O)NHaryl, OC(S)NHC1-C20alkyl, OC(S)NHC2-C20alkenyl, OC(S)NHC2-C20 alkynyl, OC(S)NHcycloalky and, OC(S)NHaryl, or R21 and R22 taken together form a carbonyl group;
• R23 is selected from hydrogen, OH, OC1-C20alkyl, OC2-C20alkenyl, OC2-C20alkynyl, Ocycloalkyl, OC(O)C1-C20alkyl, OC(O)C2-C20alkenyl, OC(O)C2-C20alkynyl, OC(O)cycloalkyl, OC(O)aryl, —OC(O)NHC1-C20alkyl, OC(O)NHC2-C20alkenyl, OC(O)NHC2-C20alkynyl, OC(O)NHcycloalkyl, OC(O)NHaryl, OC(S)NHC1-C20alkyl, OC(S)NHC2-C20alkenyl, OC(S)NHC2-C20 alkynyl, OC(S)NHcycloalkyl and OC(S)NHaryl;
• R24 is selected from hydrogen, OH, OC1-C20alkyl, OC2-C20alkenyl, OC2-C20alkynyl, Ocycloalkyl, OC(O)C1-C20alkyl, OC(O)C2-C20alkenyl, OC(O)C2-C20 alkynyl, OC(O)cycloalkyl, —OC(O)aryl, OC(O)NHC1-C20alkyl, OC(O)NHC2-C20alkenyl, OC(O)NHC2-C20alkynyl, OC(O)NHcycloalkyl, OC(O)NHaryl, OC(S)NHC1-C20alkyl, OC(S)NHC2-C20alkenyl, OC(S)NHC2-C20 alkynyl, OC(S)NHcycloalkyl and OC(S)NHaryl;
• R25 is selected from hydrogen and —C1-C10alkyl;
• R26 and R27 are independently selected from hydrogen, —C1-C10alkyl, —OH, —OC1-C10alkyl;
• wherein each alkyl, alkenyl, alkynyl, cycloalkyl and aryl is optionally substituted with one or more optional substituents, wherein each optional substituent is independently —F, —Cl, —Br, —I, —CN, —CF3, —CO2R28, —COR28, —OR28, —SR28, —N(R28)2, —NO2, —NR28OR28, —ON(R28)2, —SOR28, —SO2R28, —SO3R28, —SON(R28)2, —SO3N(R28)2, —P(R28)3, —P(°O)(R28)3, —OSi(R28)3, —OB(R28)2 and wherein R28 is hydrogen, —C1-C6 alkyl, —C2-C6alkenyl, —C2-C6alkynyl, —C3-C8cycloalkyl, arylalkyl, —C1-C6 haloalkyl, —C1-C6dihaloalkyl or —C1-C6trihaloalkyl;
• or a geometric isomer or stereoisomer thereof or a pharmaceutically, acceptable salt thereof.