Cytostatic agents

The use of a compound of formula (I) or a pharmaceutically acceptable salt hydrate or solvate thereof in the preparation of a pharmaceutical composition for inhibiting proliferation of tumour cells in mammals:

• 57
• wherein
• R is hydrogen or (C1-C6)alkyl:
• R1 is hydrogen;
• (C1-C6)alkyl or fluoro-substituted (C1-C6)alkyl;
• (C2-C6)alkenyl;
• phenyl or substituted phenyl;
• phenyl(C1-C6)alkyl or substituted phenyl(C1-C6)alkyl;
• phenyl(C2-C6)alkenyl or substituted phenyl(C2-C6)alkenyl heterocyclyl or substituted heterocyclyl;
• heterocyclyl(C1-C6)alkyl or substituted heterocyclyl(C1-C6)alkyl;
• a group BSOnA- wherein n is 0, 1 or 2 and B is hydrogen or a (C1-C6) alkyl, phenyl, substituted phenyl, heterocyclyl substituted heterocyclyl, (C1-C6)acyl, phenacyl or substituted phenacyl group, and A represents (C1-C6)alkylene;
• amino(C1-C6)alkyl, (C1-C6)alkylamino(C1-C6)alkyl, di(C1-C6)alkylamino(C1-C6)alkyl, hydroxy(C1-C6)alkyl, mercapto(C1-C6)alkyl or carboxy(C1-C6) alkyl wherein the amino-, hydroxy-, mercapto- or carboxyl-group are optionally protected or the carboxyl- group amidated;
• lower alkyl substituted by carbamoyl, mono(lower alkyl)carbamoyl, di(lower alkyl)carbamoyl, di(lower alkyl)amino, or carboxy-lower alkanoylamino;
• a cycloalkyl, cycloalkenyl, cycloalkyl(C1-C6alkyl), cycloalkenyl(C1-C6alkyly or non-aromatic heterocyclic ring containing up to 3 heteroatoms, any of which may be (i) substituted by one or more substituents selected from C1-C6 alkyl, C2-C6 alkenyl, halo, cyano (—CN), —CO2H, —CO2R, —CONH2, —CONHR, —CON(R)2, —OH, —OR, oxo-, —SH, —SR, —NHCOR, and —NHCO2R wherein R is C1-C6 alkyl or benzyl and/or (ii) fused to a cycloalkyl or heterocyclic ring;
• R2 is a C1-C12 alkyl,
• C2-C12 alkenyl,
• C2-C12 alkynyl,
• phenyl(C1-C6 alkyl),
• heteroaryl(C1-C6 alkyly,
• phenyl(C2-C6 alkenyly,
• heteroaryl(C2-C6 alkenyly,
• phenyl(C2-C6 alkynyly,
• heteroaryl(C2-C6 alkynyly,
• cycloalkyl(C1-C6 alkyly,
• cycloalkyl(C2-C6 alkenyly,
• cycloalkyl(C2-C6 alkynyly,
• cycloalkenyl(C1-C6 alkyl),
• cycloalkenyl(C2-C6 alkenyl),
• cycloalkenyl(C2-C6 alkynyl),
• phenyl(C1-C6 alkyl)O(C1-C6 alkyl), or
• heteroaryl(C1-C6 alkyl)O(C1-C6 alkyl) group,
• any one of which may be optionally substituted by
• C1-C6 alkyl,
• C1-C6 alkoxy,
• halo,
• cyano (—CN),
• phenyl or heteroaryl, optionally ring-substituted by
• C1-C6 alkyl,
• C1-C6 alkoxy,
• halo, or
• cyano (—CN);
• R3 is the characterising group of a natural or non-natural a amino acid in which any functional groups may be protected;
• and
• R4 is an ester or thioester group.