Depsipeptides and their therapeutic use

A compound of the general Structure VIII

• including pharmaceutically acceptable salts thereof, wherein
• R1, R2 (where X=—CONR6−), and R3 are the same or different and each represents an amino-acid side chain moiety selected from the group consisting of:
• —H, —C1-C6 alkyl, —C2-C6 alkenyl, -L′-O—C(O)—R′, -L′-C(O)—O—R″, -L′-A, -L′-N R″R″, -L′-Het-C(O)-Het-R″ and -L′-Het-R″, wherein L′ is a C2-C6 alkylene group and A is phenyl or a 5- to 6-membered heteroaryl group, each R′ is the same or different and represents C1-C4 alkyl, each R″ is the same or different and represents H or C1-C6 alkyl, each Het is the same or different and is a heteroatom spacer selected from —O—, —N(R″)— and —S—, and each R″′ is the same or different and represents H or C1-C4 alkyl;
• Z is a heteroatom bonded to the macrocycle by a single or double bond, and any other group bonded to Z is H or a protecting group;
• R2 (where X=—CHZ—), R4 and R6 are the same or different and each represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl or, C2-C6 alkynyl;
• K represents a linear or branched chain of 1-10 atoms containing carbon atoms and other atoms;
• M is a linear or branched chain containing 1-10 carbon or other atoms, and is capable of undergoing in vivo cleavage to give the following Structure VII:
• wherein the variables are as defined above and R7 is selected from —H, —C1-C6 alkyl, —C2-C6 alkenyl or -L′-A and L represents SPr1, wherein Pr1 is H or a protecting group that forms a thioether, a monothio, dithio or aminothioacetal, a thioester or a carbamine acid thioester to protect a thiol group.