Anhydride modified cantharidin analogues useful in the treatment of cancer
AssigneeThe University of Newcastle Research Associates Limited
InventorsAdam McCluskey, Jennette A. Sakoff, Stephen Ackland, Alistair T.R. Sim
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Abstract
Anhydride modified cantharidin analogues useful in the treatment of certain forms of cancer also methods for the screening for anti-cancer activity of these analogues and/or their ability to sensitise cancer cells to cancer treatment. The modified cantharidin analogues have structure (I) or (II), wherein R1, R2, R3 and R4 are H, aryl or alkyl; X is O, N or S; Y is O, S, NH, NR; R is alkyl or aryl; A and B are H or CH3; W and Z are CHOH or C═O. These compounds inhibit protein phosphatase. 1
Claims29
A cell permeable inhibitor of protein phosphatase, said inhibitor being an anhydride modified cantharidin analogue.
A compound of the formula:
- 31
- wherein R1 and R2 are H. aryl or alkyl;
- X is O, N or S;
- Y is O, S, SR, NH, NR, CH2OH, CH2OR;
- R is alkyl or aryl;
- A and B are H or CH3;
- W and Z are CHOH or C=0 and R1 and R2 can cyclise to form a ring as follows:
- 32
- wherein R3 and R4 are H, aryl or alkyl.
A process for producing anhydride modified cantharidin analogues for use in the treatment of cancer or for the sensitising cancer cells to one or more cancer treatments comprising the step of reacting a diene with an ene.
A process for producing anhydride modified cantharidin analogues, said process including the steps of:
- dissolving a diene in a suitable solvent and adding to the resultant solution an ene.
A process for producing anhydride modified cantharidin analogue, said process including the steps of:
- dissolving a furan in a suitable solvent and adding to the resultant solution an ene;
- incubating the solution at a temperature and for a time sufficient to form a precipitate;
- and
- collecting the precipitate and recrystalising the analogue.
A process for producing anhydride modified cantharidin analogue, said process including the steps of:
- mixing thiophene and maleic anhydride at room temperature in a suitable solvent;
- compressing the mixture at a temperature and pressure sufficient to facilitate a reaction to take place;
- and
- purifying the analogue.
A method of screening compounds for use in sensitising cancer cells to at least one method of treating cancer, and comprising:
- screening for anti-cancer activity;
- and
- screening for ability to abrogate either the G1 or the G2 checkpoint of the cancer cell cycle.
A compound selected from a group comprising compounds (a) to (k) below:
- 33 34
Dependencies are inferred from the claim text.