Micheliolide derivatives, methods for their preparation and their use as anticancer and antiinflammatory agents

A compound of one of general formula (A) and general formula (B), or a pharmaceutically acceptable salt thereof,

• A is ═CH2 or —CH2R* wherein R* is an amino acid residue bonded to the A methylene via a nitrogen or sulfur atom;
• or R* is —NR1R2, —NR1C(O)R2, —NR1CO2R2, or —SR1, wherein R1 and R2 are independently selected from the group consisting of H and an optionally substituted alkyl, alkenyl, or alkynyl group, an optionally substituted heteroalkyl, heteroalkenyl, or heteroalkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted heterocyclic group;
• or R* is —NR′R2, wherein R1 and R2 optionally together with the nitrogen atom form an optionally substituted 5-12 membered ring, the ring optionally comprising at least one heteroatom or group selected from the group consisting of —CO—, —SO—, —SO2—, and —PO—;
• L is —O—, —NH—, —NHC(O)—, —OC(O)—, —OC(O)NH—, —S—, —SO—, —SO2—, —PO—, —OCH2—, or a chemical bond connecting the carbon atom to Y;
• and
• Y represents an optionally substituted alkyl, alkenyl, or alkynyl group, an optionally substituted heteroalkyl, heteroalkenyl, or heteroalkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted heterocyclic group, wherein -L-Y together with the carbon atom at position C2 optionally forms carbonyl;
• or
• Y is absent and L represents a halogen atom, an azido group (—N3), an optionally substituted triazole group, or a group —NR3R4, where R3 represents a hydrogen atom or an optionally substituted alkyl, alkenyl, or alkynyl group;
• R4 represents an optionally substituted alkyl, alkenyl, alkynyl, aryl, or heteroaryl group;
• or where R3 and R4 are connected together to form an optionally substituted heterocyclic group;
• M is —O— or —OC(O)— and X represents a hydrogen atom, an optionally substituted alkyl, alkenyl, or alkynyl group, an optionally substituted heteroalkyl, heteroalkenyl, or heteroalkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted heterocyclic group.