6-ETHER/THIOETHER-PURINES AS TOPOISOMERASE II CATALYTIC INHIBITORS AND THEIR USE IN THERAPY

1 . A compound selected from compounds of the following formulae, and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof, for use in a method of treatment or therapy of the human or animal body:

wherein:

J is independently:

—H, or

NR N1 R N2 .

X is independently:

—O—, or

—S—;

Q is independently:

a covalent bond,

C 1-7 alkylene,

C 2-7 alkenylene,

C 2-7 alkynylene,

C 3-7 cycloalkylene,

C 3-7 cycloalkenylene, or

C 3-7 cycloalkynylene;

T is independently:

a group A 1 , or

a group A 2 ;

A 1 is independently:

C 6-14 carboaryl,

C 5-14 heteroaryl,

C 3-12 carbocyclic, or

C 3-12 heterocyclic;

and is independently unsubstituted or substituted;

A 2 is independently:

—H,

—CN,

—OH, or

—O(C═O)—C 1-7 alkyl;

R N is independently —H or a nitrogen ring substituent;

R 8 is independently —H or a ring substituent;

either: each of R N1 and R N2 is independently —H or a nitrogen substituent;

or: R N1 and R N2 taken together with the nitrogen atom to which they are attached form a ring having from 3 to 7 ring atoms.

2 . A compound according to claim 1 , wherein X is independently —O—.

3 . A compound according to claim 1 , wherein X is independently —S—.

4 . A compound according to claim 1 , wherein Q is independently a covalent bond.

5 . A compound according to claim 1 , wherein Q is independently C 1-7 alkylene, C 2-7 alkenylene, C 2-7 alkynylene, C 3-7 cycloalkylene, C 3-7 cycloalkenylene, or C 3-7 cycloalkynylene.

6 . A compound according to claim 1 , wherein Q is independently C 1-7 alkylene, C 2-7 alkenylene, or C 2-7 alkynylene.

7 . A compound according to claim 1 , wherein Q is independently C 1-4 alkylene, C 2-4 alkenylene, or C 2-4 alkynylene.

8 . A compound according to claim 1 , wherein Q is independently C 1-3 alkylene, C 2-3 alkenylene, or C 2-3 alkynylene.

9 . A compound according to claim 1 , wherein Q is independently selected from —(CH 2 ) n — where n is an integer from 1 to 7.

10 . A compound according to claim 1 , wherein Q is independently selected from —(CH 2 ) n — where n is an integer from 1 to 4.

11 . A compound according to claim 1 , wherein Q is independently selected from —(CH 2 ) n — where n is an integer from 1 to 3.

12 . A compound according to claim 1 , wherein Q is independently selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, and —CH 2 CH═CH—.

13 . A compound according to claim 1 , wherein J is —NR N1 R N2 .

14 . A compound according to claim 1 , wherein each of R N1 and R N2 is independently —H or a nitrogen substituent selected from:

C 1-7 alkyl;

C 2-7 alkenyl;

C 2-7 alkynyl;

C 3-7 cycloalkyl;

C 3-7 cycloalkenyl;

C 3-7 cycloalkynyl;

C 6-20 carboaryl;

C 5-20 heteroaryl;

C 3-20 heterocyclyl;

C 6-20 carboaryl-C 1-7 alkyl;

C 5-20 heteroaryl-C 1-7 alkyl;

C 3-20 heterocyclyl-C 1-7 alkyl;

and is independently unsubstituted or substituted.

15 . A compound according to claim 1 , wherein each of R N1 and R N2 is independently —H or C 1-7 alkyl, and is independently unsubstituted or substituted.

16 . A compound according to claim 1 , wherein each of R N1 and R N2 is independently —H or unsubstituted C 1-7 alkyl.

17 . A compound according to claim 1 , wherein each of R N1 and R N2 is independently —H, -Me, or -Et.

18 . A compound according to claim 1 , wherein exactly one of R N1 and R N2 is —H, and the other is a nitrogen substituent.

19 . A compound according to claim 1 , wherein neither R N1 nor R N2 is —H.

20 . A compound according to claim 1 , wherein each of R N1 and R N2 is —H.

21 . A compound according to claim 1 , wherein the group —NR N1 R N2 is independently selected from:

—NH 2 , —NHMe, —NHEt, —NH(nPr), —NH(iPr), —NH(nBu), —NH(iBu), —NH(sBu), —NH(tBu), —N(Me) 2 , —N(Et) 2 , —N(nPr) 2 , —N(iPr) 2 , —N(nBu) 2 , —N(iBu) 2 , —N(sBu) 2 , —N(tBu) 2 , —NH(Ph), —N(Ph) 2 , —NH(CH 2 Ph), —N(CH 2 Ph) 2 .

22 . A compound according to claim 1 , wherein the group —NR N1 R N2 is independently selected from: —NH 2 , —NHMe, —NHEt, —N(Me) 2 , —N(Et) 2 .

23 . A compound according to claim 1 , wherein the group —NR N1 R N2 is independently —NH 2 .

24 . A compound according to claim 1 , wherein R N1 and R N2 taken together with the nitrogen atom to which they are attached form a ring having from 3 to 7 ring atoms.

25 . A compound according to claim 1 , wherein R N1 and R N2 taken together with the nitrogen atom to which they are attached form a ring having from 5 to 7 ring atoms.

26 . A compound according to claim 1 , wherein the group —NR N1 R N2 is independently selected from:

aziridino;

azetidino;

pyrrolidin-N-yl, pyrrolin-N-yl, pyrrol-N-yl;

imidazolidin-N-yl, imidazolin-N-yl, imidazol-N-yl;

pyrazolidin-N-yl, pyrazolin-N-yl, pyrazol-N-yl;

piperidine-N-yl, piperazin-N-yl, pyridin-N-yl;

morpholino; and

azepin-N-yl.

27 . A compound according to claim 1 , wherein J is independently —H.

28 . A compound according to claim 1 , wherein R N is independently —H or a nitrogen ring substituent selected from:

C 1-7 alkyl;

C 2-7 alkenyl;

C 2-7 alkynyl;

C 3-7 cycloalkyl;

C 3-7 cycloalkenyl;

C 3-7 cycloalkynyl;

C 6-20 carboaryl;

C 5-20 heteroaryl;

C 3-20 heterocyclyl;

C 6-20 carboaryl-C 1-7 alkyl;

C 5-20 heteroaryl-C 1-7 alkyl;

C 3-20 heterocyclyl-C 1-7 alkyl;

and is independently unsubstituted or substituted.

29 . A compound according to claim 1 , wherein R N is independently —H or C 1-7 alkyl, and is independently unsubstituted or substituted.

30 . A compound according to claim 1 , wherein R N is independently —H or unsubstituted C 1-7 alkyl.

31 . A compound according to claim 1 , wherein R N is independently —H, -Me, or -Et.

32 . A compound according to claim 1 , wherein R N is independently —H.

33 . A compound according to claim 1 , wherein R N is independently —H or tetrahydrofuranyl, and is independently unsubstituted or substituted.

34 . A compound according to claim 1 , wherein R N is independently —H or morpholino-methyl, piperidino-methyl, or piperazino-methyl, and is independently unsubstituted or substituted.

35 . A compound according to claim 1 , wherein R N is independently selected from:

36 . A compound according to claim 1 , wherein T is independently A 1 .

37 . A compound according to claim 1 , wherein A 1 is independently:

C 6-14 carboaryl, or

C 5-14 heteroaryl;

and is independently unsubstituted or substituted.

38 . A compound according to claim 1 , wherein A 1 is independently:

C 6-12 carboaryl, or

C 5-12 heteroaryl;

and is independently unsubstituted or substituted.

39 . A compound according to claim 1 , wherein A 1 is independently:

C 6-10 carboaryl, or

C 5-10 heteroaryl;

and is independently unsubstituted or substituted.

40 . A compound according to claim 1 , wherein A 1 is independently:

monocyclic or bicyclic C 6-10 carboaryl, or

monocyclic or bicyclic C 5-10 heteroaryl;

and is independently unsubstituted or substituted.

41 . A compound according to claim 1 , wherein A 1 is independently:

monocyclic C 6 carboaryl, or

monocyclic C 5-6 heteroaryl;

and is independently unsubstituted or substituted.

42 . A compound according to claim 1 , wherein A 1 is independently: phenyl, naphthyl, pyridyl, pyrimidyl, pyrrolyl, imidazolyl, furanyl, thienyl, thiazoyl, or benzofurazanyl; and is independently unsubstituted or substituted.

43 . A compound according to claim 1 , wherein A 1 is independently: phenyl, naphthyl, pyrididyl, pyrrolyl, furanyl, thienyl, and thiazolyl; and is independently unsubstituted or substituted.

44 . A compound according to claim 1 , wherein A 1 is independently: phenyl, pyrimidyl, imidazolyl, or benzofurazanyl; and is independently unsubstituted or substituted.

45 . A compound according to claim 1 , wherein A 1 is independently phenyl; and is independently unsubstituted or substituted.

46 . A compound according to claim 1 , wherein A 1 is independently pyrimidyl; and is independently unsubstituted or substituted.

47 . A compound according to claim 1 , wherein A 1 is independently imidazolyl; and is independently unsubstituted or substituted.

48 . A compound according to claim 1 , wherein A 1 is independently benzofurazanyl; and is independently unsubstituted or substituted.

49 . A compound according to claim 1 , wherein A 1 is independently:

C 3-12 carbocyclic, or

C 3-12 heterocyclic;

and is independently unsubstituted or substituted.

50 . A compound according to claim 1 , wherein A 1 is independently:

C 5-10 carbocyclic, or

C 5-10 heterocyclic;

and is independently unsubstituted or substituted.

51 . A compound according to claim 1 , wherein A 1 is independently:

monocyclic or bicyclic C 3-12 carbocyclic, or

monocyclic or bicyclic C 3-12 heterocyclic;

and is independently unsubstituted or substituted.

52 . A compound according to claim 1 , wherein A 1 is independently:

C 5-8 carbocyclic, or

C 5-8 heterocyclic;

and is independently unsubstituted or substituted.

53 . A compound according to claim 1 , wherein A 1 is independently:

monocyclic C 5-8 carbocyclic, or

monocyclic C 5-8 heterocyclic;

and is independently unsubstituted or substituted.

54 . A compound according to claim 1 , wherein A 1 is independently: cyclopentyl, cyclohexyl, tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, pyrrolidinyl, piperidinyl, or piperzinyl; and is independently unsubstituted or substituted.

55 . A compound according to claim 1 , wherein A 1 is independently cyclohexyl; and is independently unsubstituted or substituted.

56 . A compound according to claim 1 , wherein substituents on the cyclic group A 1 , if present, are independently selected from:

(1) carboxylic acid; (2) ester; (3) amido or thioamido; (4) acyl; (5) halo; (6) cyano; (7) nitro; (8) hydroxy; (9) ether; (10) thiol; (11) thioether; (12) acyloxy; (13) carbamate; (14) amino; (15) acylamino orthioacylamino; (16) aminoacylamino or aminothioacylamino; (17) sulfonamino; (18) sulfonyl; (19) sulfonate; (20) sulfonamido; (21) oxo; (22) imino; (23) hydroxyimino; (24) C 5-20 aryl-C 1-7 alkyl; (25) C 5-20 aryl; (26) C 3-20 heterocyclyl; (27) C 1-7 alkyl; (28) bi-dentate di-oxy groups.

57 . A compound according to claim 1 , wherein substituents on the cyclic group A 1 , if present, are independently selected from:

(1) —C(═O)OH;

(2) —C(═O)OR 1 , wherein R 1 is independently as defined in (24), (25), (26) or (27);

(3) —C(═O)NR 2 R 3 or —C(═S)NR 2 R 3 , wherein each of R 2 and R 3 is independently —H; or as defined in (24), (25), (26) or (27); or R 2 and R 3 taken together with the nitrogen atom to which they are attached form a ring having from 3 to 7 ring atoms;

(4) —C(═O)R 4 , wherein R 4 is independently —H, or as defined in (24), (25), (26) or (27);

(5) —F, —Cl, —Br, —I;

(6) —CN;

(7) —NO 2 ;

(8) —OH;

(9) —OR 5 , wherein R 5 is independently as defined in (24), (25), (26) or (27);

(10) —SH;

(11) —SR 6 , wherein R 6 is independently as defined in (24), (25), (26) or (27);

(12) —OC(═O)R 7 , wherein R 7 is independently as defined in (24), (25), (26) or (27);

(13) —OC(═O)NR 8 R 9 , wherein each of R 8 and R 9 is independently —H; or as defined in (24), (25), (26) or (27); or R 8 and R 9 taken together with the nitrogen atom to which they are attached form a ring having from 3 to 7 ring atoms;

(14) —NR 10 R 11 , wherein each of R 10 and R 11 is independently —H; or as defined in (24), (25), (26) or (27); or R 10 and R 11 taken together with the nitrogen atom to which they are attached form a ring having from 3 to 7 ring atoms;

(15) —NR 12 C(═O)R 13 or —NR 12 C(═S)R 13 , wherein R 12 is independently —H; or as defined in (24), (25), (26) or (27); and R 13 is independently —H, or as defined in (24), (25), (26) or (27);

(16) —NR 14 C(═O)NR 15 R 16 or —NR 14 C(═S)NR 15 R 16 , wherein R 14 is independently —H; or as defined in (24), (25), (26) or (27); and each of R 15 and R 16 is independently —H; or as defined in (24), (25), (26) or (27); or R 15 and R 16 taken together with the nitrogen atom to which they are attached form a ring having from 3 to 7 ring atoms;

(17) —NR 17 SO 2 R 18 , wherein R 17 is independently —H; or as defined in (24), (25), (26) or (27); and R 18 is independently —H, or as defined in (24), (25), (26) or (27);

(18) —SO 2 R 19 , wherein R 19 is independently as defined in (24), (25), (26) or (27);

(19) —OSO 2 R 20 and wherein R 20 is independently as defined in (24), (25), (26) or (27);

(20) —SO 2 NR 21 R 22 , wherein each of R 21 and R 22 is independently —H; or as defined in (24), (25), (26) or (27); or R 21 and R 22 taken together with the nitrogen atom to which they are attached form a ring having from 3 to 7 ring atoms;

(21) ═O;

(22) ═NR 23 , wherein R 23 is independently —H; or as defined in (24), (25), (26) or (27);

(23) ═NOR 24 , wherein R 24 is independently —H; or as defined in (24), (25), (26) or (27);

(24) C 5-20 aryl-C 1-7 alkyl, for example, wherein C 5-20 aryl is as defined in (25); unsubstituted or substituted, e.g., with one or more groups as defined in (1) to (28);

(25) C 5-20 aryl, including C 6-20 carboaryl and C 5-20 heteroaryl; unsubstituted or substituted, e.g., with one or more groups as defined in (1) to (28);

(26) C 3-20 heterocyclyl; unsubstituted or substituted, e.g., with one or more groups as defined in (1) to (28);

(27) C 1-7 alkyl, C 2-7 alkenyl, C 2-7 alkynyl, C 3-7 cycloalkyl, C 3-7 cycloalkenyl, C 3-7 cycloalkynyl, unsubstituted or substituted, e.g., with one or more groups as defined in (1) to (26) and

(28) —O—R 25 —O—, wherein R 25 is independently saturated C 1-3 alkyl, and is independently unsubstituted or substituted with one or more (e.g., 1, 2, 3, 4) substituents as defined in (5).

58 . A compound according to claim 57 , wherein (27) C 1-7 alkyl, unsubstituted or substituted is:

Unsubstituted C 1-7 alkyl;

halo-C 1-7 alkyl;

amino-C 1-7 alkyl;

amido-C 1-7 alkyl;

acylamido-C 1-7 alkyl;

carboxy-C 1-7 alkyl;

acyl-C 1-7 alkyl;

hydroxy-C 1-7 alkyl; and

C 1-7 alkoxy-C 1-7 alkyl.

59 . A compound according to claim 1 , wherein substituents on the cyclic group A 1 , if present, are independently selected from:

(1) —C(═O)OH;

(2) —C(═O)OMe, —C(═O)OEt, —C(═O)O(iPr), —C(═O)O(tBu); —C(═O)O(cPr); —C(═O)OCH 2 CH 2 OH, —C(═O)OCH 2 CH 2 OMe, —C(═O)OCH 2 CH 2 OEt; —C(═O)OPh, —C(═O)OCH 2 Ph;

(3) —(C═O)NH 2 , —(C═O)NMe 2 , —(C═O)NEt 2 , —(C═O)N(iPr) 2 , —(C═O)N(CH 2 CH 2 OH) 2 ; —(C═O)-morpholino, —(C═O)NHPh, —(C═O)NHCH 2 Ph;

(4) —C(═O)H, —(C═O)Me, —(C═O)Et, —(C═O)(tBu), —(C═O)-cHex, —(C═O)Ph; —(C═O)CH 2 Ph;

(5) —F, —Cl, —Br, —I;

(6) —CN;

(7) —NO 2 ;

(8) —OH;

(9) —OMe, —OEt, —O(iPr), —O(tBu), —OPh, —OCH 2 Ph; —OCF 3 , —OCH 2 CF 3 ; —OCH 2 CH 2 OH, —OCH 2 CH 2 OMe, —OCH 2 CH 2 OEt; —OCH 2 CH 2 NH 2 , —OCH 2 CH 2 NMe 2 , —OCH 2 CH 2 N(iPr) 2 ; —OPh-Me, —OPh-OH, —OPh-OMe, —OPh-F, —OPh-Cl, —OPh-Br, —OPh-I;

(10) —SH;

(11) —SMe, —SEt, —SPh, —SCH 2 Ph;

(12) —OC(═O)Me, —OC(═O)Et, —OC(═O)(iPr), —OC(═O)(tBu); —OC(═O)(cPr); —OC(═O)CH 2 CH 2 OH, —OC(═O)CH 2 CH 2 OMe, —OC(═O)CH 2 CH 2 OEt; —OC(═O)Ph, —OC(═O)CH 2 Ph;

(13) —OC(═O)NH 2 , —OC(═O)NHMe, —OC(═O)NMe 2 , —OC(═O)NHEt, —OC(═O)NEt 2 , —OC(═O)NHPh, —OC(═O)NCH 2 Ph;

(14) —NH 2 , —NHMe, —NHEt, —NH(iPr), —NMe 2 , —NEt 2 , —N(iPr) 2 , —N(CH 2 CH 2 OH) 2 ; —NHPh, —NHCH 2 Ph; piperidino, piperazino, morpholino;

(15) —NH(C═O)Me, —NH(C═O)Et, —NH(C═O) n Pr, —NH(C═O)Ph, —NHC(═O)CH 2 Ph; —NMe(C═O)Me, —NMe(C═O)Et, —NMe(C═O)Ph, —NMeC(═O)CH 2 Ph;

(16) —NH(C═O)NH 2 , —NH(C═O)NHMe, —NH(C═O)NHEt, —NH(C═O)NPh, —NH(C═O)NHCH 2 Ph; —NH(C═S)NH 2 , —NH(C═S)NHMe, —NH(C═S)NHEt, —NH(C═S)NPh, —NH(C═S)NHCH 2 Ph;

(17) —NHSO 2 Me, —NHSO 2 Et, —NHSO 2 Ph, —NHSO 2 PhMe, —NHSO 2 CH 2 Ph; —NMeSO 2 Me, —NMeSO 2 Et, —NMeSO 2 Ph, —NMeSO 2 PhMe, —NMeSO 2 CH 2 Ph;

(18) —SO 2 Me, —SO 2 CF 3 , —SO 2 Et, —SO 2 Ph, —SO 2 PhMe, —SO 2 CH 2 Ph;

(19) —OSO 2 Me, —OSO 2 CF 3 , —OSO 2 Et, —OSO 2 Ph, —OSO 2 PhMe, —OSO 2 CH 2 Ph;

(20) —SO 2 NH 2 , —SO 2 NHMe, —SO 2 NHEt, —SO 2 NMe 2 , —SO 2 NEt 2 , —SO 2 -morpholino, —SO 2 NHPh, —SO 2 NHCH 2 Ph;

(21) ═O;

(22) ═NH, ═NMe; ═NEt;

(23) ═NOH, ═NOMe, ═NOEt, ═NO(nPr), ═NO(iPr), ═NO(cPr), ═NO(CH 2 -cPr);

(24) —CH 2 Ph, —CH 2 Ph-Me, —CH 2 Ph-OH, —CH 2 Ph-F, —CH 2 Ph-Cl;

(25) -Ph, -Ph-Me, -Ph-OH, -Ph-OMe, -Ph-NH 2 , -Ph-F, -Ph-Cl, -Ph-Br, -Ph-I; pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, furanyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, thiadiazolyl;

(26) pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, azepinyl, tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, azetidinyl;

(27) -Me, -Et, -nPr, -iPr, -nBu, -iBu, -sBu, -tBu, -nPe;

-cPr, -cHex; —CH═CH 2 , —CH 2 —CH═CH 2 ;

—CF 3 , —CHF 2 , —CH 2 F, —CCl 3 , —CBr 3 , —CH 2 CH 2 F, —CH 2 CHF 2 , and —CH 2 CF 3 ;

—CH 2 OH, —CH 2 OMe, —CH 2 OEt, —CH 2 NH 2 , —CH 2 NMe 2 ;

—CH 2 CH 2 OH, —CH 2 CH 2 OMe, —CH 2 CH 2 OEt, —CH 2 CH 2 CH 2 NH 2 , —CH 2 CH 2 NMe 2 ;

(28) —O—CH 2 —O—, —O—CH 2 —CH 2 —O—, —O—CH 2 —CH 2 —CH 2 —O—, —O—CF 2 —O—, and —O—CF 2 —CF 2 —O—.

60 . A compound according to claim 1 , wherein substituents on the cyclic group A 1 , if present, are independently selected from:

(2) —C(═O)OMe, —C(═O)OEt;

(5) —F, —Cl, —Br, —I;

(7) —NO 2 ;

(8) —OH;

(9) —OMe, —OEt;

(11) —SMe, —SEt;

(12) —OC(═O)Me, —OC(═O)Et;

(14) —NH 2 , —NHMe, —NHEt, —NMe 2 , —NEt 2 ;

(27) -Me, and -Et.

61 . A compound according to claim 1 , wherein T, is independently A 2 .

62 . A compound according to claim 61 , wherein A 2 is independently:

—H;

—CN;

—OH; or

—O(C═O)—C 1-7 alkyl.

63 . A compound according to claim 61 , wherein A 2 , is independently:

—H;

—CN;

—OH; or

—O(C═O)—C 1-7 alkyl;

with the proviso that Q is not a covalent bond.

64 . A compound according to claim 61 , wherein A 2 is independently —H, with the proviso that Q is not a covalent bond.

65 . A compound according to claim 61 , wherein A 2 is independently —CN, with the proviso that Q is not a covalent bond.

66 . A compound according to claim 61 , wherein A 2 is independently —OH or —O(C═O)—C 1-7 alkyl, with the proviso that Q is not a covalent bond.

67 . A compound according to claim 61 , wherein A 2 is independently —OH or —O(C═O)Me, with the proviso that Q is not a covalent bond.

68 . A compound according to claim 1 , wherein R 8 is independently —H or a monovalent monodentate substituent selected from those defined for (1) through (20) and (24) through (27) in any one of claims 56 to 60 .

69 . A compound according to claim 1 , wherein R 8 is independently —H.

70 . A compound according to claim 1 , selected from the following compounds, and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof:

NU2058

O 6 -benzylguanine

NSC35866

NSC15747

NSC35865

NSC36824

NSC39328

NSC46384

71 . A compound according to claim 1 , selected from the following compounds, and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof:

NSC244708

NSC172614

NSC42375

NSC52383

NSC38732

NSC52388

NSC348401

NSC348402

NSC348400

72 . A compound according to claim 1 , selected from the following compounds, and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof:

NSC35862

NSC39331

NSC647471

73 . A compound as defined in claim 1 for use in combination with a topoisomerase II poison in a method of treatment of the human or animal body by therapy.

74 . A compound according to claim 73 , wherein the topoisomerase II poison is an anthracycline or an epipodophyllotoxin.

75 . A compound according to claim 73 , wherein the topoisomerase II poison is an anthracycline selected from: doxorubicin, idarubicin, epirubicin, aclarubicin, mitoxantrone, dactinomycin, bleomycin, mitomycin, carubicin, pirarubicin, daunorubicin, daunomycin, 4-iodo-4-deoxy-doxorubicin, N,N-dibenzyl-daunomycin, morpholinodoxorubicin, aclacinomycin, duborimycin, menogaril, nogalamycin, zorubicin, marcellomycin, detorubicin, annamycin, 7-cyanoquinocarcinol, deoxydoxorubicin, valrubicin, GPX-100, MEN-10755, and KRN5500.

76 . A compound according to claim 73 , wherein the topoisomerase II poison is an epipodophyllotoxin selected from: etoposide, etoposide phosphate, teniposide, tafluposide, VP-16213, and NK-611.

77 . A compound according to claim 73 , wherein the topoisomerase II poison is etoposide.

78 . Use of a compound as defined in claim 1 in the manufacture of a medicament for use in the treatment of a disease or condition that is ameliorated by the catalytic inhibition of topoisomerase II.

79 . Use according to claim 78 , wherein the treatment is prevention or treatment of tissue damage associated with extravasation of a topoisomerase II poison.

80 . Use according to claim 78 , wherein the treatment is prevention or treatment of tissue damage associated with extravasation of a topoisomerase II poison in a patient receiving treatment with said topoisomerase II poison.

81 . Use according to claim 79 , wherein the medicament is for systemic administration.

82 . Use according to claim 79 , wherein the medicament is for local administration.

83 . Use according to claim 79 , wherein the topoisomerase II poison is an anthracycline or an epipodophyllotoxin.

84 . Use according to claim 79 , wherein the topoisomerase II poison is an anthracycline selected from: doxorubicin, idarubicin, epirubicin, aclarubicin, mitoxantrone, dactinomycin, bleomycin, mitomycin, carubicin, pirarubicin, daunorubicin, daunomycin, 4-iodo-4-deoxy-doxorubicin, N,N-dibenzyl-daunomycin, morpholinodoxorubicin, aclacinomycin, duborimycin, menogaril, nogalamycin, zorubicin, marcellomycin, detorubicin, annamycin, 7-cyanoquinocarcinol, deoxydoxorubicin, valrubicin, GPX-100, MEN-10755, and KRN5500.

85 . Use according to claim 79 , wherein the topoisomerase II poison is an epipodophyllotoxin selected from: etoposide, etoposide phosphate, teniposide, tafluposide, VP-16213, and NK-611.

86 . Use according to claim 79 , wherein the topoisomerase II poison is etoposide.

87 . Use of a compound as defined in claim 1 in the manufacture of a medicament for use in combination with a topoisomerase II poison, in the treatment of a disease or condition that is ameliorated by the catalytic inhibition of topoisomerase II.

88 . Use according to claim 87 , wherein the treatment is treatment of a proliferative condition.

89 . Use according to claim 87 , wherein the treatment is treatment of cancer.

90 . Use according to claim 87 , wherein the treatment is treatment of solid tumour cancer.

91 . Use according to claim 87 , wherein the treatment is treatment of a proliferative condition of the central nervous system (CNS).

92 . Use according to claim 87 , wherein the treatment is treatment of a tumour of the central nervous system (CNS).

93 . Use according to claim 87 , wherein the treatment is treatment of brain cancer.

94 . Use according to claim 87 , wherein the topoisomerase II poison is an anthracycline or an epipodophyllotoxin.

95 . Use according to claim 87 , wherein the topoisomerase II poison is an anthracycline selected from: doxorubicin, idarubicin, epirubicin, aclarubicin, mitoxantrone, dactinomycin, bleomycin, mitomycin, carubicin, pirarubicin, daunorubicin, daunomycin, 4-iodo-4-deoxy-doxorubicin, N,N-dibenzyl-daunomycin, morpholinodoxorubicin, aclacinomycin, duborimycin, menogaril, nogalamycin, zorubicin, marcellomycin, detorubicin, annamycin, 7-cyanoquinocarcinol, deoxydoxorubicin, valrubicin, GPX-100, MEN-10755, and KRN5500.

96 . Use according to claim 87 , wherein the topoisomerase II poison is an epipodophyllotoxin selected from: etoposide, etoposide phosphate, teniposide, tafluposide, VP-16213, and NK-611.

97 . Use according to claim 87 , wherein the topoisomerase II poison is etoposide.

98 . A method of inhibiting topoisomerase II in a cell, in vitro or in vivo, comprising contacting the cell with an effective amount of a compound as defined in claim 1 .

99 . A method of treatment comprising administering to a patient in need of treatment a therapeutically effective amount of a compound as defined in claim 1 .

100 . A method of treatment comprising administering to a patient in need of treatment a therapeutically effective amount of a compound as defined in claim 1 and a topoisomerase II poison.

101 . A method of targeting the cytotoxicity of a topoisomerase II poison, comprising administering a compound as defined in claim 1 , in combination with said topoisomerase II poison.

102 . A method according to claim 101 , wherein the targeting is targeting to a solid tumour.

103 . A method according to claim 101 , wherein the targeting is targeting to the central nervous systems (CNS).

104 . A method of permitting increased dosage of a topoisomerase II poison in therapy, comprising administering a compound as defined in claim 1 , in combination with said topoisomerase II poison.