US2003171334A1PendingUtilityA1
Treatment of prostate cancer
Priority: Aug 7, 2000Filed: Aug 7, 2001Published: Sep 11, 2003
Est. expiryAug 7, 2020(expired)· nominal 20-yr term from priority
A61K 31/222A61K 47/54A61K 31/235A61K 36/47A61P 35/00A61K 47/548A61K 31/455
51
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Claims
Abstract
A chemical agent of the diterpene family obtained from a member of the Euphorbiaceae family of plants for use in the treatment of prophylaxis of prostate cancer or a related cancer or condition.
Claims
exact text as granted — not AI-modified1 . A method for the treatment or prophylaxis of prostate cancer or a related cancer or condition in a subject, said method comprising the administration to said subject of a symptom-ameliorating effective amount of a chemical agent obtainable from a plant of t h e Euphorbiaceae family or a derivative or chemical analog thereof which chemical agent is a diterpene selected from compounds of the ingenane, pepluane and jatrophane families and which chemical agent or derivative or chemical analog is represented by any one of the general formulae (a - (V):-
wherein:
n is 0-10 atoms selected from carbon, oxygen, nitrogen, sulfur, phosphorus, silicon, boron, arsenic and selenium, wherein the ring defmed by said atoms is saturated or unsaturated, including epoxides and tluoepoxides;
A-T are independently selected fiom hydrogen, R 1 , R 2 , R 3 , F, Cl, Br, I, CN, OR 1 , SR 1 , NR 1 R 2 , N(=O) 2 , NR 1 OR 2 , ONR 1 R 2 , SOR 1 , SO 2 R 1 , SO 3 R 1 , SONR 1 R 2 , SO 2 NR 1 R 2 , SO 3 NR 1 R 2 , P(R 1 ) 3 , P(=O)(R 1 ) 3 , Si(R 1 ) 3 , B(R 1 ) 2 , (C=X)R 3 or X(C=X)R 3 where X is selected from sulfur, oxygen and nitrogen;
R 1 and R 2 are each independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle, C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 alkynyl (branched and/or straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 allcoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloalkyl, haloalkoxy, C 1 -C 10 [CN, OR 1 , SR 1 , NR 1 R 2 , N(=O) 2 , NR 1 OR 2 , ONR 1 R 2 , SOR 1 , SO 2 R 1 , SO 3 R 1 , SONR 1 R 2 , SO 2 NR 1 R 2 , SO 3 NR 1 R 2 , P(R 1 ) 3 , P(=O)(R 1 ) 3 , Si(R 1 ) 3 , B(R 1 ) 2 ]alkyl;
R 3 is selected from R 1 , R 2 , CN, COR 1 , CO 2 R 1 , OR 1 , SR 1 , NR 1 R 2 , N(=O) 2 , NR 1 OR 2 , ONR 1 R 2 , SOR 1 , SO 2 R 1 , SO 3 R 1 , SONR 1 R 2 , SO 2 NR 1 R 2 , SO 3 NR 1 R 2 , P(R 1 ) 3 , P(=O)(R 1 ) 3 , Si(R 1 ) 3 , B(R 1 ) 2 ;
A connected to B (or C), D (or E), R (or Q), P (or O) or S (or T) is a selection of C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic rings further substituted by R 3 , (C=X)R 3 and X(C=X)R 3 , including epoxides and thioepoxides;
J connected to I (or H), G (or F), K (or L), M (or N) or S (or T) is a selection of C 1 -C 8 disubstituted (fused) saturated and unsaturated carbocyclic or heterocyclic rings further substituted by R 3 , (C=X)R 3 and X(C=X)R 3 , including epoxides and thioepoxides;
D (or E) connected to B (or C) or G (or F); I (or H) connected to G (or F); P (or O) connected to R (or Q) or M (or N); K (or L) connected to N (or M) is a selection of C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic rings substituted by R 3 , (C=X)R 3 and X(C=X)R 3 , including epoxides and thioepoxides;
B and C, D and E, R and Q, P and O, I and H, G and F, K and L M and N or S and T are =X where X is selected from sulfur, oxygen, nitrogen, NR 1 R 2 , and =Cr 1 R 2
wherein:
n is 0-10 atoms seleeted from carbon, oxygen, nitrogen, sulfur, phosphorus, silicon, boron, arsenic and selenium, wherein the ring defined by said atoms is saturated or unsaturated, including epoxides and thioepoxides;
A′-T′ are independently selected from hydrogen, R 4 , R 5 , R 6 , F, Cl, Br, I, CN, COR 4 , CO 2 R 4 , OR 4 , SR 4 , NR 4 R 5 , CONR 4 R 5 , N(=O) 2 , NR 4 OR 5 , ONR 4 R 5 , SOR 4 , SO 2 R 4 , SO 3 R 4 , SONR 4 R 5 , SO 2 NR 4 R 5 , SO 3 NR 4 R 5 , P(R 4 ) 3 , P(=O)(R 4 ) 3 , Si(R 4 ) 3 , B(R 4 ) 2 , (C=X)R 6 or X(C=X)R 6 where X is selected from sulfur, oxygen and nitrogen;
R 4 and R 5 are each, independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle, C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 alkynyl (branched and/or straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloalkyl, haloalkoxy, C 1 -C 10 [CN, OR 4 , SR 4 , NR 4 R 5 , N(=O) 2 , NR 4 RO 5 , ONR 4 R 5 , SOR 4 , SO 2 R 4 , SO 3 R 4 , SONR 4 R 5 , SO 2 NR 4 R 5 , SO 3 NR 4 R 5 , P(R 4 ) 3 , P(=O)(R 4 ) 3 , Si(R 4 ) 3 , B(R 4 ) 2 ]alkyl;
R 6 is selected from R 4 , R 5 , CN, COR 4 , CO 2 R 4 , OR 4 , SR 4 , NR 4 R 5 , N(=O) 2 , NR 4 OR 5 , ONR 4 R 5 , SOR 4 , SO 2 R 4 , SO 3 R 4 , SONR 4 R 5 , SO 2 NR 4 R 5 , SO 3 NR 5 , P(R 4 ) 3 , P(=O)(R 4 ) 3 , Si(R 4 ) 3 , B(R 4 ) 2 ;
E′ and R′ or H′ and O′ is a C 2 -C 8 saturated or unsaturated carbocyclic or heterocyclic ring system further substituted by R 6 , including epoxides and thioepoxides;
O′ connected to M′ (or N′) or Q′ (or P′); R′ connected to Q′ 60 (or P′) or S′ (or T′); S′ (or T′) connected to A′ (or B′); A′ (or B′) connected to C′ (or D′); E′ connected to C′ (or D′) or F′ (or G′); H′ connected to I′; I′ connected to J′; J′ connected to K′; K′ connected to L′; L′ connected to M′ (or N′) are C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic ring systems further substituted by R 6 , (C=X)R 6 and X(C=X)R 6 , including epoxides and thioepoxides;
A′, B′and C′, D′and F′, G′and M′, N′and P′Q′and S′T′are =X where X is selected from sulfur, oxygen, nitrogen, NR4R 5 , (C=X)R 6 , X(CX)R 6 , and =CR 7 R 8 ; R 7 and R 8 are each independently selected from R 6 , (C=X)R 6 and X(C=X)R 6
wherein:
n is 0-10 atoms selected from carbon, oxygen, nitrogen, sulfur, phosphorus, silicon, boron, arsenic and selenium, wherein the ring defined by said atoms is saturated or unsaturated, including epoxides and thioepoxides;
A 1 -T 1 are independently selected from hydrogen, R 9 , R 10 , R 11 , F, Cl, Br, I, CN, OR 9 , SR 9 , NR 9 R 10 , N(=O) 2 , NR 9 OR 10 , ONR 9 R 10 , SOR 9 , SO 2 R 9 , SO 3 R 9 , SONR 9 R 10 , SO 2 NR 9 R 10 , SO 3 NR 9 R 10 , P(R 9 ) 3 , P(=O)(R 9 ) 3 , Si(R 9 ) 3 , B(R 9 ) 2 , (C=X)R 11 or X(C=X)R 11 , where X is selected from sulfiur, oxygen and nitrogen;
R 9 and R 10 are each independently selected from C 1 -C 20 alkyl (branched and straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -CI 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle, C 2 -C 10 alkenyl (branched and straight chained), C 2 -C 10 alkynyl (branched and straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trialoalkyl, haloalkoxy, C 1 -C 10 [CN, OR 9 , SR 9 , NR 9 R 10 , N(=O) 2 , NR 9 OR 10 , ONR 9 R 10 , SOR 9 , SO 2 R 9 , SO 3 R 9 , SONR 9 R 10 , SO 2 NR 9 R 10 , SO 3 NR 9 R 10 , P(R 9 ) 3 , P(=O)(R 9 ) 3 , Si(R 9 ) 3 , B(R 9 ) 2 ]alkyl;
R 11 , is selected from R 9 , R 10 , CN, COR 9 , CO 2 R 9 , OR 9 , SR 9 , NR 9 R 10 , N(=O) 2 , NR 9 OR 10 , ONR 9 R 10 , SOR 9 , SO 2 R 9 , SO 3 R 9 , SONR 9 R 10 , SO 2 NR 9 R 10 , SO 3 NR 9 R 10 , P(R 9 ) 3 , P(=O)(R 9 ) 3 , Si(R 9 ) 3 , B(R 9 ) 2 ;
B 1 and R 1 , E 1 and Ö 1 and Ë 1 and M 1 are selected from a C 2 -C 8 saturated or unsaturated carbocyclic or heterocyclic ring system further substituted by R 11 , including epoxides and thioepoxides;
A 1 (or Ä 1 connected to Á 1 (or à 1 ) or T 1 (or S 1 ); B 1 connected to Á 1 (or à 1 ) or C 1 (or D 1 ). E 1 connected to Ë 1 or C 1 (or D 1 ); Ë 1 connected to É 1 (or F 1 ); G 1 (or H 1 ) connected to É 1 (or F 1 ) or I 1 (or J 1 ); K 1 (or L 1 ) connected to I 1 (or J 1 ) or M 1 ; M 1 connected to O 1 (or N 1 ); Ö 1 connected O 1 (or N 1 ) or P 1 (or Q 1 ); R 1 connected P 1 (or Q 1 ) or S 1 (or T 1 ) are C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic ring systems further substituted by R 11 , (C=X)R 11 , and X(C=X)R 11 , including epoxides and thioepoxides;
A 1 , Ä and Á, Ã and C 1 , D 1 and F 1 , É and G 1 , H 1 and I 1 , J 1 and K 1 , L 1 and N 1 , O 1 and P 1 , Q 1 and S 1 , T 1 are =X where X is selected from sulfur, oxygen, nitrogen, NR 9 R 10 , including (C=X)R 11 , and X(C=X)R 11 , and =CR 12 R 13 ;
R 12 and R 13 are independently selected from R 11 , (C=X)R 11 , and X(C=X)R 11 ,
wherein:
n is 0-10 atoms selected from carbon, oxygen, nitrogen, sulfuir, phosphorus, silicon, boron, arsenic and selenium, wherein the ring defined by said atoms is saturated or unsaturated, including epoxides and thioepoxides;
A 2 -X 2 are independently selected from hydrogen, R 14 , R 15 , R 16 , F, Cl, Br, I, CN, OR 14 , SR 14 , NR 14 R 15 , N(=O) 2 , NR 14 OR 15 , ONR 14 R 15 , SOR 14 , SO 2 R 14 , SO 3 R 14 , SONR 14 R 15 , SO 2 NR 14 R 15 , SO 3 NR 14 R 15 , P(R 14 ) 3 , P(=O)(R 14 ) 3 , Si(R 14 ) 3 , B(R 14 ), (C=Y)R 16 or Y(C=Y)R 16 where Y is selected from sulfur, oxygen and nitrogen;
R 14 and R 15 are each independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 allkynyl (branched and/or straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloalkyl, haloalkoxy, C 1 -C 10 [CN, OR 14 , SR 14 , NR 14 R 10 , N(=O) 2 , NR 14 OR 15 , ONR 14 R 15 , SOR 14 , SO 2 R 14 , SO 3 R 14 , SONR 14 R 15 , SO 2 NR 14 R 15 , SO 3 NR 14 R 15 , P(R 14 ) 3 , P(=O)(R 14 ) 3 , Si(R 14 ) 3 , B(R 14 ) 2 ]alkyl;
R 16 is selected from R 14 , R 15 , CN, COR 14 , CO 2 R 15 , OR 14 , SR 14 , N 14 R 15 , N(=O) 2 , NR 14 OR 15 , ONR 14 R 15 , SOR 14 , S 2 R 14 , SO 3 R 14 , SONR 14 R 15 , SO 2 NR 14 R 15 , SO 3 NR 14 R 15 , P(R 4 ) 3 , P(=O)(R 14 ) 3 , Si(R 14 ) 3 , B(R 14 ) 2 ;
E 2 and V 2 , and H 2 and S 2 , and I 2 and P 2 are C 2 -C 8 saturated or unsaturated carbocyclic or heterocyclic ring system further substituted by R 16 , including epoxides and thioepoxides;
A 2 (or B 2 ) connected to C 2 (or D 2 ) or W 2 (or X 2 ); E 2 connected to C 2 (or D 2 ) or F 2 (or G 2 ); H 2 connected to F 2 (or G 2 or I 2 ; I 2 connected to J 2 (or K 2 ); L 2 (or M 2 ) connected to J 2 (or K 2 ) or N 2 (or O 2 ); R 2 (or Q 2 connected to P 2 or S 2 ; V 2 connected to U 2 (or T 2 ) or W 2 (or X 2 ) are C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic ring systems further substituted by R 16 , (C=Y)R 16 and Y(C=Y)R 16 , including epoxides and thioepoxides;
A 2 , B 2 ; C 2 , D 2 ; F 2 , G 2 ; J 2 , K 2 ; L 2 , M 2 ; N 2 , O 2 ; O 2 , R 2 ; U 2 , T 2 and X 2 , W 2 are =Y where Y is selected from sulfur, oxygen, nitrogen, NR 14 R 15 and =CR 17 R 18 ;
R 17 and R 18 are independently selected from R 16 , (C=Y)R 16 and Y(C=Y)R 16
wherein:
n is 0-10 atoms selected from carbon, oxygen, nitrogen, sulfuir, phosphorus, silicon, boron, arsenic and selenium, wherein the ring defined by said atoms is saturated or unsaturated, including epoxides and thioepoxides;
A 3 -Z 3 are independently selected from hydrogen, R 19 , R 20 , R 21 , F, Cl, Br, I, CN, OR 19 , SR 19 , NR 19 R 20 , N(=O) 2 , NR 19 OR 20 , ONR 19 R 20 , SOR 19 , SO 2 R 19 , SO 3 R 19 , SONR 19 R 20 , SO 2 NR 19 R 20 , SO 3 NR 19 R 20 , P(R 19 ) 3 , P(=O)(R 19 ) 3 , Si(R 19 ) 3 , B(R 19 ) 2 , (C=Ø)R 21 or Ø(C=Ø)R 21 where Ø is sulfur, oxygen and nitrogen;
R 19 and R 20 are each independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle, C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 alkynyl (branched and/or straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 allkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloalkyl, haloalkoxy, C 1 -C 10 [CN, OR 19 , SR 19 , NR 19 R 20 , N(=O) 2 , NR, 19 OR 20 , ONR 19 R 20 , SOR 19 , SO 2 R 19 , SO 3 R 19 , SONR 19 R 20 , SO 2 NR 19 R 20 , SO 3 NR 19 R 20 , P(R 19 ) 3 , P(=O)(R 19 ) 3 , Si(R 19 ) 3 , B(R 19 ) 2 ]alkyl;
R 21 is selected from R 19 , R 20 , CN, COR 19 , CO 2 R 19 , OR 19 , SR 19 , NR 19 R 20 , N(=O) 2 , NR 19 OR 20 , ONR 19 R 20 , SOR 19 , SO 2 R 19 , SO 3 R 19 , SONR 19 R 20 , SO 2 NR 19 R 20 , SO 3 NR 19 R 20 , P(R 19 ) 3 , P(=O)(R 19 ) 3 , Si(R 19 ) 3 , B(R 19 ) 2 ;
D 3 connected to X 3 is a C 2 -C 8 saturated or unsaturated carbocyclic or heterocyclic ring system further substituted by R 21 , including epoxides and thioepoxides; A 3 (or Ä 3 ) connected to B 3 (or C 3 ) or Z 3 (or Y 3 ); D 3 connected to B 3 (or C 3 ) or E 3 (or F 3 ); G 3 (or H 3 ) connected to E 3 (or F 3 ) or I 3 (or J 3 ); L 3 (or K 3 ) connected to I 3 (or J 3 ) or M 3 (or N 3 ); O 3 (or Ö 3 ) connected to N 3 (or M 3 ) or P 3 (or Q 3 ). S 3 (or R 3 ) connected to Q 3 (or P 3 ) or U 3 (or T 3 ). W 3 (or V 3 ) connected to U 3 (or T 3 ) or X 3 ; X 3 connected to Y 3 (or Z 3 ) are C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic ring systems further substituted by R 21 , (C=Ø)R 21 and Ø (C=Ø)R 21 , including epoxides and thioepoxides;
A 3 , Ä 3 ;B 3 ,C 3 ; E 3 ,F 3 ; G 3 , H 3 ; I 3 , J 3 ; K 3 , L 3 ; M 3 ,N 3 ; O 3 , {umlaut over ( 0 )} 3 ; Q 3 ,P 3 , R 3 , U 3 , T 3 , W 3 , V 3 , and Z 3 ,Y 3 are =Ø where Ø is selected from sulfur, oxygen, nitrogen, NR 19 R 20 , and =CR 22 R 23 ; and
R 22 and R 23 are selected from R 21 , (C=Ø)R 21 and Ø (C=Ø)R 21 ; and which chemical agent or derivative or chemical analog is administered for a time and under conditions sufficient to ameliorate one or more symptoms associated with said, prostate cancer or related cancer or condition.
2 . A method according to claim 1 wherein the chemical agent is represented. by the general forrnula (VI):
wherein:
R 24 , R 25 and R 26 are independently selected from hydrogen, R 27 , R 28 , F, Cl, Br, I, CN, OR 27 , SR 27 , NR 27 R 28 , N(=O) 2 , Nr 27 OR 28 , ONR 27 R 28 , SOR 27 , SO 2 R 27 , SO 3 R 27 , SONR 27 R 28 , SO 2 NR 27 R 28 , SO 3 NR 27 R 28 , P(R 27 ) 3 , P(=O)(R 27 ) 3 ,Si(R 27 ) 3 , B(R 27 ) 2 , (C=X)R 29 or X(C=X)R 29 where X is selected from sulfur, oxygen and nitrogen;
R 27 and R 28 are each independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C14 heterocycle, C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 alkynyl (branched and/or straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloalkyl, haloalkoxy, C 1 -C 10 [CN, OR 27 , SR 27 , NR 27 R 28 , N(=O) 2 , NR 27 OR 28 , ONR 27 R 28 , SOR 27 , SO 2 R 27 , SO 3 R 27 , SONR 27 R 28 , SO 2 NR 27 R 28 , SO 3 NR 27 R 28 , P(R 27 ) 3 , P(O)(R 27 ) 3 , Si(R 27 ) 3 , B(R 27 ) 2 ]alkyl;
R 29 is selected from R 27 , R 28 , CN, COR 27 , CO 2 R 27 , OR 27 , SR 27 , NR 27 R 28 , N(=O) 2 , NR 27 OR 28 , ONR 27 R 28 , SOR 27 , SO 2 R 27 , SO 3 R 27 , SONR 27 R 28 , SO 2 NR 27 R 28 , SO 3 NR 27 R 28 , P(R 27 ) 3 , P(=O)(R 27 ) 3 , Si(R 27 ) 3 , B(R 27 ) 2 .
3 . A method according to claim 2 wherein R 24 is H.
4 . A method according to claim 2 wherein R 24 is OAcetyl.
5 . A method according to claim 2 wherein R 24 is OH.
6 . A method according to claim 2 wherein R 25 is OH.
7 . A method according to claim 2 wherein R 26 is OH.
8 . A method according to claim 1 wherein the plant is of the genus selected from Acalypha, Acidoton, Actinostemon, Adelia, Adenocline, Adenocrepis, Adenophaedra, Adisca, Agrostistachys, Alchornea, Alchorneopsis, Alcinaeanthus, Alcoceria, Aleurites, Amanoa, Andrachne, Angostyles, Anisophllum, Antidesmia, Aphora, Aporosa, Aporosella, Argythamnia, Astrococcus, Astrogyne, Baccanrea, Baliospermum, Bernardia, Beyeriopsis, Bischofia, Blachia, Blumeodondron, Bonania, Bradleia, Breynia, Breyniopsis, Briedelia, Buraeavia, Caperonia, Caryodendron, Celianella, Cephalocroton, Chaenotheca, Chaetocarpus, Chanaesyce, Cheilosa, Chiropetalum, Choriophyllum, Cicca, Chaoxylon, Cleidon, Cleistanthus, Cluytia, Cnesmone, Cnidoscolus, Coccoceras, Codiaeum, Coelodiscus, Conami, Conceveiba, Conceveibastrum, Conceveibum, Corythea, Croizatia, Croton, Crotonopsis, Crozophora, Cubanthus, Cunuria, Dactylostemon, Dalechampia, Dendrocousinsia, Diaspersus, Didymocistus, Dimorphocalyx, Discocarpus, Ditaxis, Dodecastingma, Drypetes, Dysopsis, Elateriospermum, Endadenium, Endospermum, Erismanthus, Erythrocarpus, Erythrochilus, Eumecanthus, Euphorbia, Euphorbiodendron, Excoecaria, Flueggea, Calearia, Garcia, Gavarretia, Gelonium, Giara, Givotia, Glochidion, Clochidionopsis, Glycydendron, Gymnanthes, Gymnosparia, Haematospermum, Hendecandra, Hevea, Hieronima, Hieronyma, Hippocrepandra, Homalanthus, Hymenocardia, Janipha, Jatropha, Julocroton, Lasiocroton, Leiocarpus, Leonardia, Lepidanthus, Leucocroton, Mabea, Macaranga, Mallotus, Manihot, Mappa, Maprounea, Melanthesa, Mercurialis, mettenia, Micrandra, Microdesmis, Microelus, Microstachy, Maocroton, Monadenium, Mozinnia, Neoscortechinia, Omalanthus, Omphalea, Ophellantha, Orbicularia, Ostodes, Oxydectes, Palenga, Pantadenia, Paradrypeptes, Pausandra, Pedilandthus, Pera, Peridium,Petalostigima, Phyllanthus, Picrodendro, Pierardia, Pilinophytum, Pimeleodendron, Piranhea, Platygyna, Plukenetia, Podocalyx, Poinsettia, Poraresia, Prosartema, Pseudanthus, Pycnocoma, Ouadrasia, Reverchonia, Richeria, Richeriella, Ricinella,Ricinocarpus, Rottlera, Sagotia, Sanwithia, Sapium, Savia, Sclerocroton, Sebastiana, Securinega, Senefeldera, Senefilderopsis, Serophyton, Siphonia, Spathiostemon, Spixia, Stillingia, Strophioblachia, Synadenium, Tetracoccus, Tetraplandra, Tetrorchidium, Thyrsanthera, Tithymalus, Trageia, Trewia, Trigonostemon, Tyria and Xylophylla.
9 . A method according to claim 7 wherein the plant is of the genus Euphorbia.
10 . A method according to claim 8 wherein the species of Euphorbia is selected from Euphorbia aaron - rossii, Euphorbia abbreviata, Euphorbia acuta, Euphorbia alatocaulis, Euphorbia albicaulis, Euphorbia algomarginata, Euphorbia aliceae, Euphorbia alta, Euphorbia anacampseros, Euphorbia andromedae, Euphorbia angusta, Euphorbia anthonyi, Euphorbia antiguensis, Euphorbia apocynifolia, Euphorbia arabica, Euphorbia ariensis, Euphorbia arizonica, Euphorbia arkansana, Euphorbia arteagae, Euphorbia arundelana, Euphorbia astroites, Euphorbia atrococca, Euphorbia baselicis, Euphorbia batabanensis, Euphorbia bergeR 1 , Euphorbia bermudiana, Euphorbia bicolor, Euphorbia biformis, Euphorbia bifurcata, Euphorbia bilobata, Euphorbia biramensis, Euphorbia biuncialis, Euphorbia blepharostipula, Euphorbia blodgetti, Euphorbia boerhaavioides, Euphorbia boliviana, Euphorbia bracei, Euphorbia brachiata, Euphorbia brachycera, Euphorbia brandegee, Euphorbia brittonii, Euphorbia caesia, Euphorbia calcicola, Euphorbia campestris, Euphorbia candelabrum, Euphorbia capitellata, Euphorbia carmenensis, Euphorbia carunculata, Euphorbia cayensis, Euphorbia celastroides, Euphorbia chalicophila, Euphorbia chamaerrhodos, Euphorbia chamaesula, Euphorbia chiapensis, Euphorbia chiogenoides, Euphorbia cinerascens, Euphorbia clarionensis, Euphorbia colimae, Euphorbia colorata, Euphorbia communtata, Euphorbia consoquitlae, Euphorbia convolvuloides, Euphorbia corallifera, Euphorbia creberrima, Euphorbia crenulata, Euphorbia cubensis, Euphorbia cuspidata, Euphorbia cymbiformis, Euphorbia darlingtonii, Euphorbia defoliata, Euphorbia degeneR 1 , Euphorbia deltoidea, Euphorbia dentata, Euphorbia depressa Euphorbia dictyosperma, Euphorbia dictyosperma, Euphorbia dioeca, Euphorbia discoidalis, Euphorbia dorsiventralis, Euphorbia drumondii, Euphorbia duclouxii, Euphorbia dussii, Euphorbia eanophylla, Euphorbia eggersii, Euphorbia eglandulosa, Euphorbia elata, Euphorbia enzalla, Euphorbia eriogonoides, Euphorbia eriophylla, Euphorbia esculaeformis, Euphorbia espirituenisis, Euphorbia esula, Euphorbia excisa, Euphorbia exclusa, Euphorbia exstipitata, Euphorbia exstipulata, Euphorbia fendleR 1 , Euphorbia filicaulis, Euphorbia filiformis, Euphorbia florida, Euphorbia fruticulosa, Euphorbia garber, Euphorbia gaumerii, Euphorbia gerardiania, Euphorbia geyeR 1 , Euphorbia glyptosperma, Euphorbia gorgonis, Euphorbia gracilior, Euphorbia gracillima, Euphorbia gradyi, Euphorbia graminea, Euphorbia graminiea Euphorbia grisea, Euphorbia guadalajarana, Euphorbia guanarensis, Euphorbia gymnadenia, Euphorbia haematantha, Euphorbia hedyotoides, Euphorbia heldrichii, Euphorbia helenae, Euphorbia helleR 1 , Euphorbia helwigii, Euphorbia henricksonii, Euphorbia heterophylla, Euphorbia hexagona, Euphorbia hexagonoides, Euphorbia hinkleyorum, Euphorbia hintonii, Euphorbia hirtula, Euphorbia hirta, Euphorbia hooveR 1 , Euphorbia humistrata, Euphorbia hypericifolia, Euphorbia inundata, Euphorbia involuta, Euphorbia jaliscensis, Euphorbia jejuna, Euphorbia johnston, Euphorbia juttae, Euphorbia knuthii, Euphorbia lasiocarpa, Euphorbia lata, Euphorbia latazi, Euphorbia latericolor, Euphorbia laxiflora Euphorbia lecheoides, Euphorbia ledienii, Euphorbia leucophylla, Euphorbia lineata, Euphorbia linguiformis, Euphorbia longecornuta, Euphorbia longepetiolata, Euphorbia longeramosa, Euphorbia longinsulicola, Euphorbia longipila, Euphorbia lupulina, Euphorbia lurida, Euphorbia lycioides, Euphorbia macropodoides, macvaughiana, Euphorbia manca, Euphorbia mandoniania, Euphorbia mangleti, Euphorbia mango, Euphorbia marylandica, Euphorbia mayana, Euphorbia melanadenia, Euphorbia melanocarpa, Euphorbia meridensis, Euphorbia mertonii, Euphorbia mexiae, Euphorbia microcephala, Euphorbia microclada, Euphorbia micromera, Euphorbia misella, Euphorbia missurica, Euphorbia montana, Euphorbia montereyana, Euphorbia multicaulis, Euphorbia multiformis, Euphorbia multinodis, Euphorbia multiseta, Euphorbia muscicola, Euphorbia neomexicana, Euphorbia nephradenia, Euphorbia niqueroana, Euphorbia oaxacana, Euphorbia occidentalis, Euphorbia odontodemia, Euphorbia olivacea, Euphorbia olowaluana, Euphorbia opthalmica, Euphorbia ovata, Euphorbia pachypoda, Euphorbia pachyrhiza, Euphorbia padifolia, Euphorbia palmeR 1 , Euphorbia paludicola, Euphorbia paralias, Euphorbia parciflora, Euphorbia parishii, Euphorbia parryi, Euphorbia paxiana, Euphorbia pediculifera, Euphorbia peplidion, Euphorbia peploides, Euphorbia peplus, Euphorbia pergamena, Euphorbia perlignea, Euphorbia petaloidea, Euphorbia petaloidea, Euphorbia petrina, Euphorbia picachensis, Euphorbia pilosula, Euphorbia pilulifera, Euphorbia pinariona, Euphorbia pinetorum, Euphorbia pioniosperma, Euphorbia platysperma, Euphorbia plicata, Euphorbia poeppigii, Euphorbia poliosperma, Euphorbia polycarpa, Euphorbia polycnemioides, Euphorbia polyphylla, Euphorbia portoricensis, Euphorbia portulacoides Euphorbia portulana, Euphorbia preslii, Euphorbia prostrata, Euphorbia pteroneura, Euphorbia pycnanthema, Euphorbia ramosa, Euphorbia rapulum, Euphorbia remyi, Euphorbia retroscabra, Euphorbia revoluta, Euphorbia rivularis, Euphorbia robusta, Euphorbia romosa, Euphorbia rubida, Euphorbia rubrosperma, Euphorbia rupicola, Euphorbia sanmartensis, Euphorbia saxatilis M. Bieb, Euphorbia schizoloba, Euphorbia sclerocyathium, Euphorbia scopulorum, Euphorbia senilis, Euphorbia serpyllifolia, Euphorbia serrula, Euphorbia setiloba Engelm, Euphorbia sonorae, Euphorbia soobyi, Euphorbia sparsiflora, Euphorbia sphaerosperma, Euphorbia syphilitica, Euphorbia spruceana, Euphorbia subcoerulea, Euphorbia stellata, Euphorbia submammilaris, Euphorbia subpeltata, Euphorbia subpubens, Euphorbia subrenforme, Euphorbia subtrifoliata, Euphorbia succedanea, Euphorbia tamaulipasana, Euphorbia telephioides, Euphorbia tenuissima, Euphorbia tetrapora, Euphorbia tirucalli, Euphorbia tomentella, Euphorbia tomentosa, Euphorbia torralbasii, Euphorbia tovariensis, Euphorbia trachysperma, Euphorbia tricolor, Euphorbia troyana, Euphorbia tuerckheimii, Euphorbia turczaninowii, Euphorbia umbellulata, Euphorbia undulata, Euphorbia vermiformis, Euphorbia versicolor, Euphorbia villifera, Euphorbia violacea, Euphorbia whitei, Euphorbia xanti Engelm, Euphorbia xylopoda Greenm., Euphorbia yayalesia Urb., Euphorbia yungasensis, Euphorbia zeravschanica and Euphorbia zinniiflora.
11 . A method according to claim 9 wherein the species of Euphorbia is Euphorbia peplus.
12 . A method according to claim 1 wherein the cancer is prostate cancer.
13 . A method according to any one of claims 1 to 12 wherein the chemical agent is coupled to a targeting agent.
14 . A method according to claim 13 wherein the targeting agent is a bone-seeking agent.
15 . A method according to claim 14 wherein the bone-seeking agent is bisphosphonate.
16 . A method according to claim 15 wherein the bisphosphonate is methylene disphosphonate.
17 . A method according to claim 13 wherein the targeting agent is an antibody to a prostate-specific tunmor marker.
18 . A method according to claim 17 wherein the marker is prostate-specific antigen (PSA), prostate-specific membrane antigen (PMSA) or PSA receptor.
19 . A method for the treatment or prophylaxis of prostate cancer or a related cancer or condition in a subject, said method comprising the administration to said subject of a symptom-ameliorating effective amount of a chemical agent obtainable from Euphorbia peplus or a derivative or chemical analog thereof which chemical agent is a diterpene selected from compounds of the ingenane, pepluane and jatrophane faiilies and X which chemical agent or derivative or chemical analog is represented by any one of the general formulae (I)-(V):
wherein:
n is 0-10 atoms selected from carbon, oxygen, nitrogen, sulfiur, phosphorus, silicon, boron, arsenic and selenium, wherein the ring defmed by said atoms is saturated or unsaturated, including epoxides and thioepoxides;
A-T are independently selected fiom hydrogen, R 1 , R 2 , R 3 , F, Cl, Br, I, CN, OR 1 , SR 1 , NR 1 R 2 , N(=O) 2 , NR 1 OR 2 , ONR 1 R 2 , SOR 1 , SO 2 R 1 , SO 3 R 1 , SONR 1 R 2 , SO 2 NR 1 R 2 , SO 3 NR 1 R 2 , P(R 1 ) 3 , P(=O)(R 1 ) 3 , Si(R 1 ) 3 , B(R 1 ) 2 , (C=X)R 3 or X(C=X)R 3 where X is selected from sulfur, oxygen and nitrogen;
R 1 and R 2 are each independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle, C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 alkynyl (branched and/or straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 allcoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloalkyl, haloalkoxy, C 1 -C 10 [CN, OR 1 , SR 1 , NR 1 R 2 , N(=O) 2 , NR 1 OR 2 , ONR 1 R 2 , SOR 1 , SO 2 R 1 , SO 3 R 1 , SONR 1 R 2 , SO 2 NR 1 R 2 , SO 3 NR 1 R 2 , P(R 1 ) 3 , P(=O)(R 1 ) 3 , Si(R 1 ) 3 , B(R 1 ) 2 ]alkyl;
R 3 is selected from R 1 , R 2 , CN, COR 1 , CO 2 R 1 , OR 1 , SR 1 , NR 1 R 2 , N(=O) 2 , NR 1 OR 2 , ONR 1 R 2 , SOR 1 , SO 2 R 1 , SO 3 R 1 , SONR 1 R 2 , SO 2 NR 1 R 2 , SO 3 NR 1 R 2 , P(R 1 ) 3 , P(=O)(R 1 ) 3 , Si(R 1 ) 3 , B(R 1 ) 2 ;
A connected to B (or C), D (or E), R (or Q), P (or O) or S (or T) is a selection of C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic rings further substituted by R 3 , (C=X)R 3 and X(C=X)R 3 , including epoxides and thioepoxides;
J connected to I (or H), G (or F), K (or L), M (or N) or S (or T) is a selection of C 1 -C 8 disubstituted (fused) saturated and unsaturated carbocyclic or heterocyclic rings further substituted by R 3 , (C=X)R 3 and X(C=X)R 3 , including epoxides and thioepoxides;
D (or E) connected to B (or C) or G (or F); I (or H) connected to G (or F); P (or O) connected to R (or Q) or M (or N); K (or L) connected to N (or M) is a selection of C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic rings substituted by R 3 , (C=X)R 3 and X(C=X)R 3 , including epoxides and thioepoxides;
B and C, D and E, R and Q, P and O, I and H, G and F, K and L M and N or S and T are =X where X is selected from sulfur, oxygen, nitrogen, NR 1 R 2 , and =CriR 2
wherein:
n is 0-10 atoms selected from carbon, oxygen, nitrogen, sulfur, phosphorus, silicon, boron, arsenic and selenium, wherein the ring defined by said atoms is saturated or unsaturated, including epoxides and thioepoxides;
A′-T′ are independently selected from hydrogen, R 4 , R 5 , R 6 , F, Cl, Br, I, CN, COR 4 , CO 2 R 4 , OR 4 , SR 4 , NR 4 R 5 , CONR 4 R 5 , N(=O) 2 , NR 4 OR 5 , ONR 4 R 5 , SOR 4 , SO 2 R 4 , SO 3 R 4 , SONR 4 R 5 , SO 2 NR 4 R 5 , SO 3 NR 4 R 5 , P(R 4 ) 3 , P(=O)(R 4 ) 3 , Si(R 4 ) 3 , B(R 4 ) 2 , (C=X)R 6 or X(C=X)R 6 where X is selected from sulfur, oxygen and nitrogen;
R 4 and R 5 are each, independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle, C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 alkynyl (branched and/or straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloalkyl, haloalkoxy, C 1 -C 10 [CN, OR 4 , SR 4 , NR 4 R 5 , N(=O) 2 , NR 4 RO 5 , ONR 4 R 5 , SOR 4 , SO 2 R 4 , SO 3 R 4 , SONR 4 R 5 , SO 2 NR 4 R 5 , SO 3 NR 4 R 5 , P(R 4 ) 3 , P(=O)(R 4 ) 3 , Si(R 4 ) 3 , B(R 4 ) 2 ]alkyl;
R 6 is selected from R 4 , R 5 , CN, COR 4 , CO 2 R 4 , OR 4 , SR 4 , NR 4 R 5 , N(=O) 2 , NR 4 OR 5 , ONR 4 R 5 , SOR 4 , SO 2 R 4 , SO 3 R 4 , SONR 4 R 5 , SO 2 NR 4 R 5 , SO 3 NR 5 , P(R 4 ) 3 , P(=O)(R 4 ) 3 , Si(R 4 ) 3 , B(R 4 ) 2 ;
E′ and R′ or H′ and O′ is a C 2 -C 8 saturated or unsaturated carbocyclic or heterocyclic ring system further substituted by R 6 , including epoxides and thioepoxides;
O′ connected to M′ (or N′) or Q′ (or P′); R′ connected to Q′ 60 (or P′) or S′ (or T′); S′ (or T′) connected to A′ (or B′); A′ (or B′) connected to C′ (or D′); E′ connected to C′ (or D′) or F′ (or G′); H′ connected to I′; I′ connected to J′; J′ connected to K′; K′ connected to L′; L′ connected to M′ (or N′) are C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic ring systems further substituted by R 6 , (C=X)R 6 and X(C=X)R 6 , including epoxides and thioepoxides;
A′, B′and C′, D′and F′, G′and M′, N′and P′Q′and S′T′are =X where X is selected from sulfur, oxygen, nitrogen, NR4R 5 , (C=X)R 6 , X(CX)R 6 , and =CR 7 R 8 ; R 7 and R 8 are each independently selected from R 6 , (C=X)R 6 and X(C=X)R 6
wherein:
n is 0-10 atoms selected from carbon, oxygen, nitrogen, sulfur, phosphorus, silicon, boron, arsenic and selenium, wherein the ring defined by said atoms is saturated or unsaturated, including epoxides and thioepoxides;
A 1 -T 1 are independently selected from hydrogen, R 9 , R 10 , R 11 , F, Cl, Br, I, CN, OR 9 , SR 9 , NR 9 R 10 , N(=O) 2 , NR 9 OR 10 , ONR 9 R 10 , SOR 9 , SO 2 R 9 , SO 3 R 9 , SONR 9 R 10 , SO 2 NR 9 R 10 , SO 3 NR 9 R 10 , P(R 9 ) 3 , P(=O)(R 9 ) 3 , Si(R 9 ) 3 , B(R 9 ) 2 , (C=X)R 11 or X(C=X)R 11 , where X is selected from sulfiur, oxygen and nitrogen;
R 9 and R 10 are each independently selected from C 1 -C 20 alkyl (branched and straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -CI 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle, C 2 -C 10 alkenyl (branched and straight chained), C 2 -C 10 alkynyl (branched and straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trialoalkyl, haloalkoxy, C 1 -C 10 [CN, OR 9 , SR 9 , NR 9 R 10 , N(=O) 2 , NR 9 OR 10 , ONR 9 R 10 , SOR 9 , SO 2 R 9 , SO 3 R 9 , SONR 9 R 10 , SO 2 NR 9 R 10 , SO 3 NR 9 R 10 , P(R 9 ) 3 , P(=O)(R 9 ) 3 , Si(R 9 ) 3 , B(R 9 ) 2 ]alkyl;
R 11 , is selected from R 9 , R 10 , CN, COR 9 , CO 2 R 9 , OR 9 , SR 9 , NR 9 R 10 , N(=O) 2 , NR 9 OR 10 , ONR 9 R 10 , SOR 9 , SO 2 R 9 , SO 3 R 9 , SONR 9 R 10 , SO 2 NR 9 R 10 , SO 3 NR 9 R 10 , P(R 9 ) 3 , P(=O)(R 9 ) 3 , Si(R 9 ) 3 , B(R 9 ) 2 ;
B 1 and R 1 , E 1 and Ö 1 and Ë 1 and M 1 are selected from a C 2 -C 8 saturated or unsaturated carbocyclic or heterocyclic ring system further substituted by R 11 , including epoxides and thioepoxides;
A 1 (or Ä 1 connected to Á 1 (or à 1 ) or T 1 (or S 1 ); B 1 connected to Á 1 (or à 1 ) or C 1 (or D 1 ). E 1 connected to Ë 1 or C 1 (or D 1 ); Ë 1 connected to É 1 (or F 1 ); G 1 (or H 1 ) connected to É 1 (or F 1 ) or I 1 (or J 1 ); K 1 (or L 1 ) connected to I 1 (or J 1 ) or M 1 ; M 1 connected to O 1 (or N 1 ); Ö 1 connected O 1 (or N 1 ) or P 1 (or Q 1 ); R 1 connected P 1 (or Q 1 ) or S 1 (or T 1 ) are C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic ring systems further substituted by R 11 , (C=X)R 11 , and X(C=X)R 11 , including epoxides and thioepoxides;
A 1 , Ä and Á, Ã and C 1 , D 1 and F 1 , É and G 1 , H 1 and I 1 , J 1 and K 1 , L 1 and N 1 , O 1 and P 1 , Q 1 and S 1 , T 1 are =X where X is selected from sulfur, oxygen, nitrogen, NR 9 R 10 , including (C=X)R 11 , and X(C=X)R 11 , and =CR 12 R 13 ;
R 12 and R 13 are independently selected from R 11 , (C=X)R 11 , and X(C=X)R 11 ,
wherein:
n is 0-10 atoms selected fiom carbon, oxygen, nitrogen, sulfur, phosphorus, silicon, boron, arsenic and selenium, wherein the ring defined by said atoms is saturated or unsaturated, including epoxides and thioepoxides;
A 2 -X 2 are independently selected from hydrogen, R 14 , R 15 , R 16 , F, Cl, Br, I, CN, OR 14 , SR 14 , NR 14 R 15 , N(=O) 2 , NR 14 OR 15 , ONR 14 R 15 , SOR 14 , SO 2 R 14 , SO 3 R 14 , SONR 14 R 15 , SO 2 NR 14 R 15 , SO 3 NR 14 R 15 , P(R 14 ) 3 , P(=O)(R 14 ) 3 , Si(R 14 ) 3 , B(R 14 ), (C=Y)R 16 or Y(C=Y)R 16 where Y is selected from sulfur, oxygen and nitrogen;
R 14 and R 15 are each independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 allkynyl (branched and/or straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloalkyl, haloalkoxy, C 1 -C 10 [CN, OR 14 , SR 14 , NR 14 R 10 , N(=O) 2 , NR 14 OR 15 , ONR 14 R 15 , SOR 14 , SO 2 R 14 , SO 3 R 14 , SONR 14 R 15 , SO 2 NR 14 R 15 , SO 3 NR 14 R 15 , P(R 14 ) 3 , P(=O)(R 14 ) 3 , Si(R 14 ) 3 , B(R 14 ) 2 ]alkyl;
R 16 is selected from R 14 , R 15 , CN, COR 14 , CO 2 R 15 , OR 14 , SR 14 , N 14 R 15 , N(=O) 2 , NR 14 OR 15 , ONR 14 R 15 , SOR 14 , S 2 R 14 , SO 3 R 14 , SONR 14 R 15 , SO 2 NR 14 R 15 , SO 3 NR 14 R 15 , P(R 4 ) 3 , P(=O)(R 14 ) 3 , Si(R 14 ) 3 , B(R 14 ) 2 ;
E 2 and V 2 , and H 2 and S 2 , and I 2 and P 2 are C 2 -C 8 saturated or unsaturated carbocyclic or heterocyclic ring system further substituted by R 16 , including epoxides and thioepoxides;
A 2 (or B 2 ) connected to C 2 (or D 2 ) or W 2 (or X 2 ); E 2 connected to C 2 (or D 2 ) or F 2 (or G 2 ); H 2 connected to F 2 (or G 2 or I 2 ; I 2 connected to J 2 (or K 2 ); L 2 (or M 2 ) connected to J 2 (or K 2 ) or N 2 (or O 2 ); R 2 (or Q 2 connected to P 2 or S 2 ; V 2 connected to U 2 (or T 2 ) or W 2 (or X 2 ) are C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic ring systems further substituted by R 16 , (C=Y)R 16 and Y(C=Y)R 16 , including epoxides and thioepoxides;
A 2 , B 2 ; C 2 , D 2 ; F 2 , G 2 ; J 2 , K 2 ; L 2 , M 2 ; N 2 , O 2 ; O 2 , R 2 ; U 2 , T 2 and X 2 , W 2 are =Y where Y is selected from sulfur, oxygen, nitrogen, NR 14 R 15 and =CR 17 R 18 ;
R 17 and R 18 are independently selected from R 16 , (C=Y)R 16 and Y(C=Y)R 16
wherein:
n is 0-10 atoms selected from carbon, oxygen, nitrogen, sulfur, phosphorus, silicon, boron, arsenic and selenium, wherein the ring defined by said atoms is saturated or unsaturated, including epoxides and thioepoxides;
A 3 -Z 3 are independently selected from hydrogen, R 19 , R 20 , R 21 , F, Cl, Br, I, CN, OR 19 , SR 19 , NR 19 R 20 , N(=O) 2 , NR 19 OR 20 , ONR 19 R 20 , SOR 19 , SO 2 R 19 , SO 3 R 19 , SONR 19 R 20 , SO 2 NR 19 R 20 , SO 3 NR 19 R 20 , P(R 19 ) 3 , P(=O)(R 19 ) 3 , Si(R 19 ) 3 , B(R 19 ) 2 , (C=Ø)R 21 or Ø (C=Ø)R 21 where Ø is sulfur, oxygen and nitrogen;
R 19 and R 20 are each independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle, C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 alkynyl (branched and/or straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 allkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloalkyl, haloalkoxy, C 1 -C 10 [CN, OR 19 , SR 19 , NR 19 R 20 , N(=O) 2 , NR, 19 OR 20 , ONR 19 R 20 , SOR 19 , SO 2 R 19 , SO 3 R 19 , SONR 19 R 20 , SO 2 NR 19 R 20 , SO 3 NR 19 R 20 , P(R 19 ) 3 , P(=O)(R 19 ) 3 , Si(R 19 ) 3 , B(R 19 ) 2 ]alkyl;
R 21 is selected from R 19 , R 20 , CN, COR 19 , CO 2 R 19 , OR 19 , SR 19 , NR 19 R 20 , N(=O) 2 , NR 19 OR 20 , ONR 19 R 20 , SOR 19 , SO 2 R 19 , SO 3 R 19 , SONR 19 R 20 , SO 2 NR 19 R 20 , SO 3 NR 19 R 20 , P(R 19 ) 3 , P(=O)(R 19 ) 3 , Si(R 19 ) 3 , B(R 19 ) 2 ;
D 3 connected to X 3 is a C 2 -C 8 saturated or unsaturated carbocyclic or heterocyclic ring system further substituted by R 21 , including epoxides and thioepoxides; A 3 (or Ä 3 ) connected to B 3 (or C 3 ) or Z 3 (or Y 3 ); D 3 connected to B 3 (or C 3 ) or E 3 (or F 3 ); G 3 (or H 3 ) connected to E 3 (or F 3 ) or I 3 (or J 3 ); L 3 (or K 3 ) connected to I 3 (or J 3 ) or M 3 (or N 3 ); O 3 (or Ö 3 ) connected to N 3 (or M 3 ) or P 3 (or Q 3 ). S 3 (or R 3 ) connected to Q 3 (or P 3 ) or U 3 (or T 3 ). W 3 (or V 3 ) connected to U 3 (or T 3 ) or X 3 ; X 3 connected to Y 3 (or Z 3 ) are C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic ring systems further substituted by R 21 , (C=Ø)R 21 and Ø (C=Ø)R 21 , including epoxides and thioepoxides;
A 3 , A 3 ;B 3 ,C 3 ; E 3 ,F 3 ; G 3 , H 3 ; I 3 , J 3 ; K 3 , L 3 ; M 3 ,N 3 ; O 3 , {umlaut over ( 0 )} 3 ; Q 3 ,P 3 , R 3 , U 3 , T 3 , W 3 , V 3 , and Z 3 ,Y 3 are =Ø where Ø is selected from sulfur, oxygen, nitrogen, NR 19 R 20 , and =CR 22 R 23 ; and
R 22 and R 23 are selected from R 21 , (C=Ø)R 21 and Ø (C=Ø)R 21 ; and which chemical agent or derivative or chemical analogis administered for a time and under conditions sufficient to ameliorate one or more symptoms associated with said prostate cancer or related cancer or condition.
20 . A method according to claim 19 wherein the chemical agent is represented by the general formula (VI):
wherein:
R 24 , R 25 and R 26 are independently selected from hydrogen, R 27 , R 28 , F, Cl, Br, I, CN, OR 27 , SR 27 , NR 27 R 28 , N(=O) 2 , Nr 27 OR 28 , ONR 27 R 28 , SOR 27 , SO 2 R 27 , SO 3 R 27 , SONR 27 R 28 , SO 2 NR 27 R 28 , SO 3 NR 27 R 28 , P(R 27 ) 3 , P(=O)(R 27 ) 3 ,Si(R 27 ) 3 , B(R 27 ) 2 , (C=X)R 29 or X(C=X)R 29 where X is selected from sulfur, oxygen and nitrogen;
R 27 and R 28 are each independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C14 heterocycle, C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 alkynyl (branched and/or straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloalkyl, haloalkoxy, C 1 -C 10 [CN, OR 27 , SR 27 , NR 27 R 28 , N(=O) 2 , NR 27 OR 28 , ONR 27 R 28 , SOR 27 , SO 2 R 27 , SO 3 R 27 , SONR 27 R 28 , SO 2 NR 27 R 28 , SO 3 NR 27 R 28 , P(R 27 ) 3 , P(O)(R 27 ) 3 , Si(R 27 ) 3 , B(R 27 ) 2 ]alkyl;
R 29 is selected from R 27 , R 28 , CN, COR 27 , CO 2 R 27 , OR 27 , SR 27 , NR 27 R 28 , N(=O) 2 , NR 27 OR 28 , ONR 27 R 28 , SOR 27 , SO 2 R 27 , SO 3 R 27 , SONR 27 R 28 , SO 2 NR 27 R 28 , SO 3 NR 27 R 28 , P(R 27 ) 3 , P(=O)(R 27 ) 3 , Si(R 27 ) 3 , B(R 27 ) 2 .
21 . A method according to claim 20 wherein R 24 is H.
22 . A method according to claim 20 wherein R 24 is OAcetyl.
23 . A method according to claim 20 wherein R 24 is OH.
24 . A method according to claim 20 wherein R 25 is OH.
25 . A method according to claim 20 wherein R 26 is OH.
26 . A method according to claim 19 wherein the cancer is prostate cancer.
27 . A method according to any one of claims 19 to 26 wherein the chemical agent is coupled to a targeting agent.
28 . A method according to claim 27 wherein the targeting agent is a bone-seeking agent.
29 . A method according to claim 28 wherein the bone-seelking agent is bisphosphonate.
30 . A method according to claim 29 wherein the bisphosphonate is methylene disphosphonate.
31 . A method according to claim 27 wherein the targeting agent is an antibody to a prostate-specific tumor marker.
32 . A method according to claim 31 wherein the marker is prostate-specific antigen (PSA), prostate-specific membrane antigen (PMSA) or PSA receptor.
33 . A method for the immunopotentiation of a subject in the treatment or prophylaxis of prostate cancer or a related condition, said method comprising the administration to said subject of a symptom-ameliorating effective amount of a chemical agent obtainable from a plant of the Euphorbiaceae fanily or a derivative or chemical analog thereof which chenical agent is a diterpene selected from compounds of the ingenane, pepluane and jatrophane families and which chemical agent or derivative or chemical analog is represented by any one of the general formulae (I)-(V):-
wherein:
n is 0-10 atoms selected from carbon, oxygen, nitrogen, sulfur, phosphorus, silicon, boron, arsenic and selenium, wherein the ring defined by said atoms is saturated or unsaturated, including epoxides and thioepoxides;
A-T are independently selected from hydrogen, R 1 , R 2 , R 3 , F, Cl, Br, I, CN, OR 1 , SR 1 , NR 1 R 2 , N(=O) 2 , NR 1 OR 2 , ONR 1 R 2 , SOR 1 , SO 2 R 1 , SO 3 R 1 , SONR 1 R 2 , SO 2 NR 1 R 2 , SO 3 NR 1 R 2 , P(R 1 ) 3 , P(=O)(R 1 ) 3 , Si(R 1 ) 3 , B R1)2, (C=X)R 3 or X(C=X)R 3 where X is selected from sulfuir, oxygen and nitrogen;
R 1 and R 2 are each independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle, C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 alkynyl (branched andlor straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloallkyl, haloalkoxy, C 1 -C 10 [CN, OR 1 , SR 1 , NR 1 R 2 , N(=O) 2 , NR 1 OR 2 , ONR 1 R 2 , SOR 1 , SO 2 R 1 , SO 3 R 1 , SONR 1 R 2 , SO 2 NR 1 R 2 , SO 3 NR 1 R 2 , P(R 1 ) 3 , P(=O)(R 1 ) 3 , Si(R 1 ) 3 , B(R 1 ) 2 ]alkyl;
R 3 is selected from R 1 , R 2 , CN, COR 1 , CO 2 R 1 , OR 1 , SR 1 , NR 1 R 2 , N(=O) 2 , NR 1 OR 2 , ONR 1 R 2 , SOR 1 , SO 2 R 1 , SO 3 R 1 , SONR 1 R 2 , SO 2 NR 1 R 2 , SO 3 NR 1 R 2 , P(R 1 ) 3 , P(=O)(R 1 ) 3 , Si(R 1 ) 3 , B(R 1 ) 2 ;
A connected to B (or C), D (or E), R (or Q), P (or O) or S (or T) is a selection of C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic rings further substituted by R 3 , (C=X)R 3 and X(C=X)R 3 , including epoxides and thioepoxides;
J connected to I (or H), G (or F), K (or L), M (or N) or S (or T) is a selection of C 1 -C 8 disubstituted (fused) saturated and unsaturated carbocyclic or heterocyclic rings further substituted by R 3 , (C=X)R 3 and X(C=X)R 3 , including epoxides and thioepoxides;
D (or E) connected to B (or C) or G (or F); I (or H) connected to G (or F); P (or O) connected to R (or Q) or M (or N); K (or L) connected to N (or M) is a selection of C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic rings substituted by R 3 , (C=X)R 3 and X(C=X)R 3 , including epoxides and thioepoxides;
B and C, D and E, R and Q, P and O, I and H, G and F, K and L, M and N or S and T are =X where X is selected from sulfur, oxygen, nitrogen, NR 1 R 2 , and =Cr 1 R 2
wherein:
n is 0-10 atoms selected from carbon, oxygen, nitrogen, sulfiu, phosphorus, silicon, boron, arsenlic and selenium, wherein the ring defined by said atoms is saturated or unsaturated, including epoxides and thioepoxides;
A′-T′ are independently selected from hydrogen, R 4 , R 5 , R 6 , F, Cl, Br, I, CN, COR 4 , CO 2 R 4 , OR 4 , SR 4 , NR 4 R 5 , CONR 4 R 5 , N(=O) 2 , NR 4 OR 5 , ONR 4 R 5 , SOR 4 , SO 2 R 4 , SO 3 R 4 , SONR 4 R 5 , SO 2 NR 4 R 5 , SO 3 NR 4 R 5 , P(R 4 ) 3 , P(=O)(R 4 ) 3 , Si(R 4 ) 3 , B(R 4 ) 2 , (C=X)R 6 or X(C=X)R 6 where X is selected from sulfur, oxygen and nitrogen;
R 4 and R 5 are each, independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle, C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 alkynyl (branched and/or straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloalkyl, haloalkoxy, C 1 -C 10 [CN, OR 4 , SR 4 , NR 4 R 5 , N(=O) 2 , NR 4 RO 5 , ONR 4 R 5 , SOR 4 , SO 2 R 4 , SO 3 R 4 , SONR 4 R 5 , SO 2 NR 4 R 5 , SO 3 NR 4 R 5 , P(R 4 ) 3 , P(=O)(R 4 ) 3 , Si(R 4 ) 3 , B(R 4 ) 2 ]alkyl;
R 6 is selected from R 4 , R 5 , CN, COR 4 , CO 2 R 4 , OR 4 , SR 4 , NR 4 R 5 , N(=O) 2 , NR 4 OR 5 , ONR 4 R 5 , SOR 4 , SO 2 R 4 , SO 3 R 4 , SONR 4 R 5 , SO 2 NR 4 R 5 , SO 3 NR 5 , P(R 4 ) 3 , P(=O)(R 4 ) 3 , Si(R 4 ) 3 , B(R 4 ) 2 ;
E′ and R′ or H′ and O′ is a C 2 -C 8 saturated or unsaturated carbocyclic or heterocyclic ring system further substituted by R 6 , including epoxides and thioepoxides;
O′ connected to M′ (or N′) or Q′ (or P′); R′ connected to Q′ 60 (or P′) or S′ (or T′); S′ (or T′) connected to A′ (or B′); A′ (or B′) connected to C′ (or D′); E′ connected to C′ (or D′) or F′ (or G′); H′ connected to I′; I′ connected to J′; J′ connected to K′; K′ connected to L′; L′ connected to M′ (or N′) are C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic ring systems further substituted by R 6 , (C=X)R 6 and X(C=X)R 6 , including epoxides and thioepoxides;
A′, B′and C′, D′and F′, G′and M′, N′and P′Q′and S′T′are =X where X is selected from sulfur, oxygen, nitrogen, NR4R 5 , (C=X)R 6 , X(CX)R 6 , and =CR 7 R 8 ; R 7 and R 8 are each independently selected from R 6 , (C=X)R 6 and X(C=X)R 6
wherein:
n is 0-10 atoms selected from carbon, oxygen, nitrogen, sulfur, phosphorus, silicon, boron, arsenic and selenium, wherein the ring defined by said atoms is saturated or unsaturated, including epoxides and thioepoxides;
A 1 -T 1 are independently selected from hydrogen, R 9 , R 10 , R 11 , F, Cl, Br, I, CN, OR 9 , SR 9 , NR 9 R 10 , N(=O) 2 , NR 9 OR 10 , ONR 9 R 10 , SOR 9 , SO 2 R 9 , SO 3 R 9 , SONR 9 R 10 , SO 2 NR 9 R 10 , SO 3 NR 9 R 10 , P(R 9 ) 3 , P(=O)(R 9 ) 3 , Si(R 9 ) 3 , B(R 9 ) 2 , (C=X)R 11 or X(C=X)R 11 , where X is selected from sulfiur, oxygen and nitrogen;
R 9 and R 10 are each independently selected from C 1 -C 20 alkyl (branched and straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -CI 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle, C 2 -C 10 alkenyl (branched and straight chained), C 2 -C 10 alkynyl (branched and straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trialoalkyl, haloalkoxy, C 1 -C 10 [CN, OR 9 , SR 9 , NR 9 R 10 , N(=O) 2 , NR 9 OR 10 , ONR 9 R 10 , SOR 9 , SO 2 R 9 , SO 3 R 9 , SONR 9 R 10 , SO 2 NR 9 R 10 , SO 3 NR 9 R 10 , P(R 9 ) 3 , P(=O)(R 9 ) 3 , Si(R 9 ) 3 , B(R 9 ) 2 ]alkyl;
R 11 , is selected from R 9 , R 10 , CN, COR 9 , CO 2 R 9 , OR 9 , SR 9 , NR 9 R 10 , N(=O) 2 , NR 9 OR 10 , ONR 9 R 10 , SOR 9 , SO 2 R 9 , SO 3 R 9 , SONR 9 R 10 , SO 2 NR 9 R 10 , SO 3 NR 9 R 10 , P(R 9 ) 3 , P(=O)(R 9 ) 3 , Si(R 9 ) 3 , B(R 9 ) 2 ;
B 1 and R 1 , E 1 and Ö 1 and Ë 1 and M 1 are selected from a C 2 -C 8 saturated or unsaturated carbocyclic or heterocyclic ring system further substituted by R 11 , including epoxides and thioepoxides;
A 1 (or Ä 1 connected to Á 1 (or à 1 ) or T 1 (or S 1 ); B 1 connected to Á 1 (or à 1 ) or C 1 (or D 1 ). E 1 connected to Ë 1 or C 1 (or D 1 ); Ë 1 connected to É 1 (or F 1 ); G 1 (or H 1 ) connected to É 1 (or F 1 ) or I 1 (or J 1 ); K 1 (or L 1 ) connected to I 1 (or J 1 ) or M 1 ; M 1 connected to O 1 (or N 1 ); Ö 1 connected O 1 (or N 1 ) or P 1 (or Q 1 ); R 1 connected P 1 (or Q 1 ) or S 1 (or T 1 ) are C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic ring systems further substituted by R 11 , (C=X)R 11 , and X(C=X)R 11 , including epoxides and thioepoxides;
A 1 , Ä and Á, Ã and C 1 , D 1 and F 1 , É and G 1 , H 1 and I 1 , J 1 and K 1 , L 1 and N 1 , O 1 and P 1 , Q 1 and S 1 , T 1 are =X where X is selected from sulfur, oxygen, nitrogen, NR 9 R 10 , including (C=X)R 11 , and X(C=X)R 11 , and =CR 12 R 13 ;
R 12 and R 13 are independently selected from R 11 , (C=X)R 11 , and X(C=X)R 11 ,
wherein:
n is 0-10 atoms selected from carbon, oxygen, nitrogen, sulfur, phosphorus, silicon, boron, arsenic and selenium, wherein the ring defined by said atoms is saturated or unsaturated, including epoxides and thioepoxides;
A 2 -X 2 are independently selected from hydrogen, R 14 , R 15 , R 16 , F, Cl, Br, I, CN, OR 14 , SR 14 , NR 14 R 15 , N(=O) 2 , NR 14 OR 15 , ONR 14 R 15 , SOR 14 , SO 2 R 14 , SO 3 R 14 , SONR 14 R 15 , SO 2 NR 14 R 15 , SO 3 NR 14 R 15 , P(R 14 ) 3 , P(=O)(R 14 ) 3 , Si(R 14 ) 3 , B(R 14 ), (C=Y)R 16 or Y(C=Y)R 16 where Y is selected from sulfur, oxygen and nitrogen;
R 14 and R 15 are each independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 allkynyl (branched and/or straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloalkyl, haloalkoxy, C 1 -C 10 [CN, OR 14 , SR 14 , NR 14 R 10 , N(=O) 2 , NR 14 OR 15 , ONR 14 R 15 , SOR 14 , SO 2 R 14 , SO 3 R 14 , SONR 14 R 15 , SO 2 NR 14 R 15 , SO 3 NR 14 R 15 , P(R 14 ) 3 , P(=O)(R 14 ) 3 , Si(R 14 ) 3 , B(R 14 ) 2 ]alkyl;
R 16 is selected from R 14 , R 15 , CN, COR 14 , CO 2 R 15 , OR 14 , SR 14 , N 14 R 15 , N(=O) 2 , NR 14 OR 15 , ONR 14 R 15 , SOR 14 , S 2 R 14 , SO 3 R 14 , SONR 14 R 15 , SO 2 NR 14 R 15 , SO 3 NR 14 R 15 , P(R 4 ) 3 , P(=O)(R 14 ) 3 , Si(R 14 ) 3 , B(R 14 ) 2 ;
E 2 and V 2 , and H 2 and S 2 , and I 2 and P 2 are C 2 -C 8 saturated or unsaturated carbocyclic or heterocyclic ring system further substituted by R 16 , including epoxides and thioepoxides;
A 2 (or B 2 ) connected to C 2 (or D 2 ) or W 2 (or X 2 ); E 2 connected to C 2 (or D 2 ) or F 2 (or G 2 ); H 2 connected to F 2 (or G 2 or I 2 ; I 2 connected to J 2 (or K 2 ); L 2 (or M 2 ) connected to J 2 (or K 2 ) or N 2 (or O 2 ); R 2 (or Q 2 connected to P 2 or S 2 ; V 2 connected to U 2 (or T 2 ) or W 2 (or X 2 ) are C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic ring systems further substituted by R 16 , (C=Y)R 16 and Y(C=Y)R 16 , including epoxides and thioepoxides;
A 2 , B 2 ; C 2 , D 2 ; F 2 , G 2 ; J 2 , K 2 ; L 2 , M 2 ; N 2 , O 2 ; O 2 , R 2 ; U 2 , T 2 and X 2 , W 2 are =Y where Y is selected from sulfur, oxygen, nitrogen, NR 14 R 15 and =CR 17 R 18 ;
R 17 and R 18 are independently selected from R 16 , (C=Y)R 16 and Y(C=Y)R 16
wherein:
n is 0-10 atoms selected from carbon, oxygen, nitrogen, sulfur, phosphorus, silicon, boron, arsenic and selenium, wherein the ring defined by said atoms is saturated or unsaturated, including epoxides and thioepoxides;
A 3 -Z 3 are independently selected from hydrogen, R 19 , R 20 , R 21 , F, Cl, Br, I, CN, OR 19 , SR 19 , NR 19 R 20 , N(=O) 2 , NR 19 OR 20 , ONR 19 R 20 , SOR 19 , SO 2 R 19 , SO 3 R 19 , SONR 19 R 20 , SO 2 NR 19 R 20 , SO 3 NR 19 R 20 , P(R 19 ) 3 , P(=O)(R 19 ) 3 , Si(R 19 ) 3 , B(R 19 ) 2 , (C=Ø)R 21 or Ø (C=Ø)R 21 where Ø is sulfur, oxygen and nitrogen;
R 19 and R 20 are each independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C 14 heterocycle, C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 alkynyl (branched and/or straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 allkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloalkyl, haloalkoxy, C 1 -C 10 [CN, OR 19 , SR 19 , NR 19 R 20 , N(=O) 2 , NR, 19 OR 20 , ONR 19 R 20 , SOR 19 , SO 2 R 19 , SO 3 R 19 , SONR 19 R 20 , SO 2 NR 19 R 20 , SO 3 NR 19 R 20 , P(R 19 ) 3 , P(=O)(R 19 ) 3 , Si(R 19 ) 3 , B(R 19 ) 2 ]alkyl;
R 21 is selected from R 19 , R 20 , CN, COR 19 , CO 2 R 19 , OR 19 , SR 19 , NR 19 R 20 , N(=O) 2 , NR 19 OR 20 , ONR 19 R 20 , SOR 19 , SO 2 R 19 , SO 3 R 19 , SONR 19 R 20 , SO 2 NR 19 R 20 , SO 3 NR 19 R 20 , P(R 19 ) 3 , P(=O)(R 19 ) 3 , Si(R 19 ) 3 , B(R 19 ) 2 ;
D 3 connected to X 3 is a C 2 -C 8 saturated or unsaturated carbocyclic or heterocyclic ring system further substituted by R 21 , including epoxides and thioepoxides; A 3 (or Ä 3 ) connected to B 3 (or C 3 ) or Z 3 (or Y 3 ); D 3 connected to B 3 (or C 3 ) or E 3 (or F 3 ); G 3 (or H 3 ) connected to E 3 (or F 3 ) or I 3 (or J 3 ); L 3 (or K 3 ) connected to I 3 (or J 3 ) or M 3 (or N 3 ); O 3 (or Ö 3 ) connected to N 3 (or M 3 ) or P 3 (or Q 3 ). S 3 (or R 3 ) connected to Q 3 (or P 3 ) or U 3 (or T 3 ). W 3 (or V 3 ) connected to U 3 (or T 3 ) or X 3 ; X 3 connected to Y 3 (or Z 3 ) are C 1 -C 8 disubstituted (fused) saturated or unsaturated carbocyclic or heterocyclic ring systems further substituted by R 21 , (C=Ø)R 21 and Ø (C=Ø)R 21 , including epoxides and thioepoxides;
A 3 , A 3 ;B 3 ,C 3 ; E 3 ,F 3 ; G 3 , H 3 ; I 3 , J 3 ; K 3 , L 3 ; M 3 ,N 3 ; O 3 , {umlaut over ( 0 )} 3 ; Q 3 ,P 3 , R 3 , U 3 , T 3 , W 3 , V 3 , and Z 3 ,Y 3 are =Ø where Ø is selected from sulfur, oxygen, nitrogen, NR 19 R 20 , and =CR 22 R 23 ; and
R 22 and R 23 are selected from R 21 , (C=Ø)R 21 and Ø (C=Ø)R 21 ; and which chemical agent or derivative or chemical analogis administered for a time and under conditions sufficient to potentiate the immune system or components therein.
34 . A method according to claim 33 wherein the chemical agent is represented by the general formula (VI):
wherein:
R 24 , R 25 and R 26 are independently selected from hydrogen, R 27 , R 28 , F, Cl, Br, I, CN, OR 27 , SR 27 , NR 27 R 28 , N(=O) 2 , Nr 27 OR 28 , ONR 27 R 28 , SOR 27 , SO 2 R 27 , SO 3 R 27 , SONR 27 R 28 , SO 2 NR 27 R 28 , SO 3 NR 27 R 28 , P(R 27 ) 3 , P(=O)(R 27 ) 3 ,Si(R 27 ) 3 , B(R 27 ) 2 , (C=X)R 29 or X(C=X)R 29 where X is selected from sulfur, oxygen and nitrogen;
R 27 and R 28 are each independently selected from C 1 -C 20 alkyl (branched and/or straight chained), C 1 -C 20 arylalkyl, C 3 -C 8 cycloalkyl, C 6 -C 14 aryl, C 1 -C 14 heteroaryl, C 1 -C14 heterocycle, C 2 -C 10 alkenyl (branched and/or straight chained), C 2 -C 10 alkynyl (branched and/or straight chained), C 1 -C 10 heteroarylalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 haloalkyl, dihaloalkyl, trihaloalkyl, haloalkoxy, C 1 -C 10 [CN, OR 27 , SR 27 , NR 27 R 28 , N(=O) 2 , NR 27 OR 28 , ONR 27 R 28 , SOR 27 , SO 2 R 27 , SO 3 R 27 , SONR 27 R 28 , SO 2 NR 27 R 28 , SO 3 NR 27 R 28 , P(R 27 ) 3 , P(O)(R 27 ) 3 , Si(R 27 ) 3 , B(R 27 ) 2 ]alkyl;
R 29 is selected from R 27 , R 28 , CN, COR 27 , CO 2 R 27 , OR 27 , SR 27 , NR 27 R 28 , N(=O) 2 , NR 27 OR 28 , ONR 27 R 28 , SOR 27 , SO 2 R 27 , SO 3 R 27 , SONR 27 R 28 , SO 2 NR 27 R 28 , SO 3 NR 27 R 28 , P(R 27 ) 3 , P(=O)(R 27 ) 3 , Si(R 27 ) 3 , B(R 27 ) 2 .
35 . A method according to claim 33 wherein R 24 is H.
36 . A method according to claim 33 wherein R 24 is OAcetyl.
37 . A method according to claim 33 wherein R 24 is OH.
38 . A method according to claim 33 wherein R 25 is OH.
39 . A method according to claim 33 wherein R 26 is OH.
40 . A method according to claim 33 wherein the plant is of the genus selected from Acalypha, Acidoton, Actinostemon, Adelia, Adenocline, Adenocrepis, Adenophaedra, Adisca, Agrostistachys, Alchornea, Alchorneopsis, Alcinaeanthus, Alcoceria, Aleurites, Amanoa, Andrachne, Angostyles, Anisophllum, Antidesmia, Aphora, Aporosa, Aporosella, Argythamnia, Astrococcus, Astrogyne, Baccanrea, Baliospermum, Bernardia, Beyeriopsis, Bischofia, Blachia, Blumeodondron, Bonania, Bradleia, Breynia, Breyniopsis, Briedelia, Buraeavia, Caperonia, Caryodendron, Celianella, Cephalocroton, Chaenotheca, Chaetocarpus, Chanaesyce, Cheilosa, Chiropetalum, Choriophyllum, Cicca, Chaoxylon, Cleidon, Cleistanthus, Cluytia, Cnesmone, Cnidoscolus, Coccoceras, Codiaeum, Coelodiscus, Conami, Conceveiba, Conceveibastrum, Conceveibum, Corythea, Croizatia, Croton, Crotonopsis, Crozophora, Cubanthus, Cunuria, Dactylostemon, Dalechampia, Dendrocousinsia, Diaspersus, Didymocistus, Dimorphocalyx, Discocarpus, Ditaxis, Dodecastingma, Drypetes, Dysopsis, Elateriospermum, Endadenium, Endospermum, Erismanthus, Erythrocarpus, Erythrochilus, Eumecanthus, Euphorbia, Euphorbiodendron, Excoecaria, Flueggea, Calearia, Garcia, Gavarretia, Gelonium, Giara, Givotia, Glochidion, Clochidionopsis, Glycydendron, Gymnanthes, Gymnosparia, Haematospermum, Hendecandra, Hevea, Hieronima, Hieronyma, Hippocrepandra, Homalanthus, Hymenocardia, Janipha, Jatropha, Julocroton, Lasiocroton, Leiocarpus, Leonardia, Lepidanthus, Leucocroton, Mabea, Macaranga, Mallotus, Manihot, Mappa, Maprounea, Melanthesa, Mercurialis, mettenia, Micrandra, Microdesmis, Microelus, Microstachy, Maocroton, Monadenium, Mozinnia, Neoscortechinia, Omalanthus, Omphalea, Ophellantha, Orbicularia, Ostodes, Oxydectes, Palenga, Pantadenia, Paradrypeptes, Pausandra, Pedilandthus, Pera, Peridium,Petalostigima, Phyllanthus, Picrodendro, Pierardia, Pilinophytum, Pimeleodendron, Piranhea, Platygyna, Plukenetia, Podocalyx, Poinsettia, Poraresia, Prosartema, Pseudanthus, Pycnocoma, Ouadrasia, Reverchonia, Richeria, Richeriella, Ricinella,Ricinocarpus, Rottlera, Sagotia, Sanwithia, Sapium, Savia, Sclerocroton, Sebastiana, Securinega, Senefeldera, Senefilderopsis, Serophyton, Siphonia, Spathiostemon, Spixia, Stillingia, Strophioblachia, Synadenium, Tetracoccus, Tetraplandra, Tetrorchidium, Thyrsanthera, Tithymalus, Trageia, Trewia, Trigonostemon, Tyria and Xylophylla.
41 . A method according to claim 40 wherein the plant is of the genus Euphorbia.
42 . A method according to claim 41 wherein the species of Euphorbia is selected from Euphorbiz aaron - rossii, Euphorbia abbreviata, Euphorbia acuta, Euphorbia alatocaulis, Euphorbia albicaulis, Euphorbia algomarginata, Euphorbia aliceae, Euphorbia alta, Euphorbia anacampseros, Euphorbia andromedae, Euphorbia angusta, Euphorbia anthonyi, Euphorbia antiguensis, Euphorbia apocynifolia, Euphorbia arabica, Euphorbia ariensis, Euphorbia arizonica, Euphorbia arkansana, Euphorbia arteagae, Euphorbia arundelana, Euphorbia astroites, Euphorbia atrococca, Euphorbia baselicis, Euphorbia batabanensis, Euphorbia bergeR 1 , Euphorbia bermudiana, Euphorbia bicolor, Euphorbia biformis, Euphorbia bifurcata, Euphorbia bilobata, Euphorbia biramensis, Euphorbia biuncialis, Euphorbia blepharostipula, Euphorbia blodgetti, Euphorbia boerhaavioides, Euphorbia boliviana, Euphorbia bracei, Euphorbia brachiata, Euphorbia brachycera, Euphorbia brandegee, Euphorbia brittonii, Euphorbia caesia, Euphorbia calcicola, Euphorbia campestris, Euphorbia candelabrum, Euphorbia capitellata, Euphorbia carmenensis, Euphorbia carunculata, Euphorbia cayensis, Euphorbia celastroides, Euphorbia chalicophila, Euphorbia chamaerrhodos, Euphorbia chamaesula, Euphorbia chiapensis, Euphorbia chiogenoides, Euphorbia cinerascens, Euphorbia clarionensis, Euphorbia colimae, Euphorbia colorata, Euphorbia communtata, Euphorbia consoquitlae, Euphorbia convolvuloides, Euphorbia corallifera, Euphorbia creberrima, Euphorbia crenulata, Euphorbia cubensis, Euphorbia cuspidata, Euphorbia cymbiformis, Euphorbia darlingtonii, Euphorbia defoliata, Euphorbia degeneR 1 , Euphorbia deltoidea, Euphorbia dentata, Euphorbia depressa Euphorbia dictyosperma, Euphorbia dictyosperma, Euphorbia dioeca, Euphorbia discoidalis, Euphorbia dorsiventralis, Euphorbia drumondii, Euphorbia duclouxii, Euphorbia dussii, Euphorbia eanophylla, Euphorbia eggersii, Euphorbia eglandulosa, Euphorbia elata, Euphorbia enzalla, Euphorbia eriogonoides, Euphorbia eriophylla, Euphorbia esculaeformis, Euphorbia espirituenisis, Euphorbia esula, Euphorbia excisa, Euphorbia exclusa, Euphorbia exstipitata, Euphorbia exstipulata, Euphorbia fendleri, Euphorbia filicaulis, Euphorbia filiformis, Euphorbia florida, Euphorbia fruticulosa, Euphorbia garber, Euphorbia gaumerii, Euphorbia gerardiania, Euphorbia geyeri, Euphorbia glyptosperma, Euphorbia gorgonis, Euphorbia gracilior, Euphorbia gracillima, Euphorbia gradyi, Euphorbia graminea, Euphorbia graminiea Euphorbia grisea, Euphorbia guadalajarana, Euphorbia guanarensis, Euphorbia gymnadenia, Euphorbia haematantha, Euphorbia hedyotoides, Euphorbia heldrichii, Euphorbia helenae, Euphorbia helleri, Euphorbia helwigii, Euphorbia henricksonii, Euphorbia heterophylla, Euphorbia hexagona, Euphorbia hexagonoides, Euphorbia hinkleyorum, Euphorbia hintonii, Euphorbia hirtula, Euphorbia hirta, Euphorbia hooveR 1 , Euphorbia humistrata, Euphorbia hypericifolia, Euphorbia inundata, Euphorbia involuta, Euphorbia jaliscensis, Euphorbia jejuna, Euphorbia johnston, Euphorbia juttae, Euphorbia knuthii, Euphorbia lasiocarpa, Euphorbia lata, Euphorbia latazi, Euphorbia latericolor, Euphorbia laxiflora Euphorbia lecheoides, Euphorbia ledienii, Euphorbia leucophylla, Euphorbia lineata, Euphorbia linguiformis, Euphorbia longecornuta, Euphorbia longepetiolata, Euphorbia longeramosa, Euphorbia longinsulicola, Euphorbia longipila, Euphorbia lupulina, Euphorbia lurida, Euphorbia lycioides, Euphorbia macropodoides, macvaughiana, Euphorbia manca, Euphorbia mandoniania, Euphorbia mangleti, Euphorbia mango, Euphorbia marylandica, Euphorbia mayana, Euphorbia melanadenia, Euphorbia melanocarpa, Euphorbia meridensis, Euphorbia mertonii, Euphorbia mexiae, Euphorbia microcephala, Euphorbia microclada, Euphorbia micromera, Euphorbia misella, Euphorbia missurica, Euphorbia montana, Euphorbia montereyana, Euphorbia multicaulis, Euphorbia multiformis, Euphorbia multinodis, Euphorbia multiseta, Euphorbia muscicola, Euphorbia neomexicana, Euphorbia nephradenia, Euphorbia niqueroana, Euphorbia oaxacana, Euphorbia occidentalis, Euphorbia odontodemia, Euphorbia olivacea, Euphorbia olowaluana, Euphorbia opthalmica, Euphorbia ovata, Euphorbia pachypoda, Euphorbia pachyrhiza, Euphorbia padifolia, Euphorbia palmeri, Euphorbia paludicola, Euphorbia paralias, Euphorbia parciflora, Euphorbia parishii, Euphorbia parryi, Euphorbia paxiana, Euphorbia pediculifera, Euphorbia peplidion, Euphorbia peploides, Euphorbia peplus, Euphorbia pergamena, Euphorbia perlignea, Euphorbia petaloidea, Euphorbia petaloidea, Euphorbia petrina, Euphorbia picachensis, Euphorbia pilosula, Euphorbia pilulifera, Euphorbia pinariona, Euphorbia pinetorum, Euphorbia pioniosperma, Euphorbia platysperma, Euphorbia plicata, Euphorbia poeppigii, Euphorbia poliosperma, Euphorbia polycarpa, Euphorbia polycnemioides, Euphorbia polyphylla, Euphorbia portoricensis, Euphorbia portulacoides Euphorbia portulana, Euphorbia preslii, Euphorbia prostrata, Euphorbia pteroneura, Euphorbia pycnanthema, Euphorbia ramosa, Euphorbia rapulum, Euphorbia remyi, Euphorbia retroscabra, Euphorbia revoluta, Euphorbia rivularis, Euphorbia robusta, Euphorbia romosa, Euphorbia rubida, Euphorbia rubrosperma, Euphorbia rupicola, Euphorbia sanmartensis, Euphorbia saxatilis M. Bieb, Euphorbia schizoloba, Euphorbia sclerocyathium, Euphorbia scopulorum, Euphorbia senilis, Euphorbia serpyllifolia, Euphorbia serrula, Euphorbia setiloba Engelm, Euphorbia sonorae, Euphorbia soobyi, Euphorbia sparsiflora, Euphorbia sphaerosperma, Euphorbia syphilitica, Euphorbia spruceana, Euphorbia subcoerulea, Euphorbia stellata, Euphorbia submammilaris, Euphorbia subpeltata, Euphorbia subpubens, Euphorbia subrenforme, Euphorbia subtrifoliata, Euphorbia succedanea, Euphorbia tamaulipasana, Euphorbia telephioides, Euphorbia tenuissima, Euphorbia tetrapora, Euphorbia tirucalli, Euphorbia tomentella, Euphorbia tomentosa, Euphorbia torralbasii, Euphorbia tovariensis, Euphorbia trachysperma, Euphorbia tricolor, Euphorbia troyana, Euphorbia tuerckheimii, Euphorbia turczaninowii, Euphorbia umbellulata, Euphorbia undulata, Euphorbia vermiformis, Euphorbia versicolor, Euphorbia villifera, Euphorbia violacea, Euphorbia whitei, Euphorbia xanti Engelm, Euphorbia xylopoda Greenm., Euphorbia yayalesia Urb., Euphorbia yungasensis, Euphorbia zeravschanica and Euphorbia zinniiflora.
43 . A method according to claim 41 wherein the species of Euphorbia is Euphorbia peplus.
44 . A method according to claim 33 wherein the cancer is prostate cancer.
45 . A method according to any one of claims 33 to 44 wherein the chemical agent is coupled to a targeting agent.
46 . A method according to claim 45 wherein the targeting agent targets a component of the immune system.
47 . A method according to claim 46 wherein the targeting agent is an immunoglobulin.
48 . A method according to claim 47 wherein the immunoglobulin targets a dendritic cell.
49 . A method according to claim 48 wherein the immunoglobulin targets a B-or T-cell.
50 . A method according to claim 1 or 33 wherein the chemical agent is a jatrophane or a derivative thereof or a pharmaceutically acceptable salt of these.
51 . A method according to claim 50 wherein said derivative is an ester derivative.
52 . A method according to claim 50 wherein said derivative is an acetylated derivative.
53 . A method according to claim 1 or 33 wherein said chemical agent is a pepluane or a derivative thereof or a pharmaceutically acceptable salt of these.
54 . A method according to claim 53 wherein said derivative is an ester derivative.
55 . A method according to claim 53 wherein said derivative is an acetylated derivative.
56 . A method according to claim 1 or 33 wherein said chemical agent is a paraliane or a derivative thereof or a pharmaceutically acceptable salt of these.
57 . A method according to claim 56 wherein said derivative is an ester derivative.
58 . A method according to claim 56 wherein said derivative is an acetylated derivative.
59 . A method according to claim 1 or 33 wherein said compound is an angeloyl-substituted ingenane or a derivative thereof or a pharmaceutically acceptable salt of these.
60 . A method according to claim 59 wherein said derivative is an acetylated derivative.
61 . A method according to claim 59 wherein said jatrophane is of conformation 2.
62 . A method according to claim 50 or 53 or 56 or 59 wherein the derivative comprises a substitution as represented in any one of general formulae (I)-(VI).
63 . A method according to claim 1 or 33 wherein said compound is 5,8,9,10,14-pentaacetoxy-3-benzoyloxy-15-hydroxypepluane (pepluane) or a derivative thereof or a pharmaceutically acceptable salt of these.
64 . A method according to claim 63 wherein said derivative is an ester derivative.
65 . A method according to claim 1 or 33 wherein said compound is 2,3,5,7,15-pentaacetoxy-9-nicotinoyloxy-14-oxojatropha-6(17),11E-diene Oatrophane 1) or a derivative thereof or a pharmaceutically acceptable salt of these.
66 . A method according to claim 65 wherein said derivative is an ester derivative.
67 . A method according to claim 1 or 33 wherein said compound is 2,5,7,8,9,14-hexaacetoxy-3-benzoyloxy- 15-hydroxyjatropha-6(17),11E-diene (jatrophane 2) or a derivative thereof or a pharmaceutically acceptable salt of these.
68 . A method according to claim 67 wherein said derivative is an ester derivative.
69 . A method according to claim 1 or 33 wherein said compound is 2,5,14-triacetoxy-3-benzoyloxy-8,15-dihydroxy-7-isobutyroyloxy-9-nicotinoyloxjatropha-6(17), 11E-diene (jatrophane 3) or a derivative thereof or a pharmaceutically acceptable salt of these.
70 . A method according to claim 69 wherein said derivative is an ester derivative.
71 . A method according to claim 1 or 33 wherein said compound is 2,5,9,14-tetraacetoxy-3-benzoyloxy-8, 15-dihydroxy-7-isobutyroyloxyatropha-6(17),11E-diene) (jatrophane 4) or a derivative thereof or a pharmaceutically acceptable salt of these.
72 . A method according to claim 71 wherein said derivative is an ester derivative.
73 . A method according to claim 1 or 33 wherein said compound is 2,5,7,14-tetraacetoxy-3-benzoyloxy-8,15-dihydroxy-9-nicotinoyloxyjatropha-6(17),11E-diene (jatrophane 5) or a derivative thereof or a pharmaceutically acceptable salt of these.
74 . A method according to claim 73 wherein said derivative is an ester derivative.
75 . A method according to claim 1 or 33 wherein said compound is 2,5,7,9,14-pentaacetoxy-3-benzoyloxy-8,15-dihydroxy atropha-6(17),11E-diene (jatrophane 6) or a derivative thereof or a pharmaceutically acceptable salt of these.
76 . A method according to claim 75 wherein said derivative is an ester derivative.
77 . A method according to claim 1 or 33 wherein said compound is 20-O-acetyl-ingenol-3-angelate or a derivative thereof or a pharmaceutically acceptable salt of these.
78 . A method according to claim 77 wherein said derivative is an ester derivative.
79 . A method according to claim 1 or 33 or 63 or 65 or 67 or 69 or 71 or 73 or 75 or 77 wherein said compound is provided in the form of a composition comprising a pharmaceutically- or cosmetically-acceptable carrier.
80 . A method for the treatment or prophylaxis of a subject with prostate cancer or a related condition or with the symptoms of prostate cancer, said method comprising the administration to said subject of a symptom-ameliorating effective amount of an angeloyl substituted ingenane or a chemical fraction or plant extract comprising same.
81 . A method for the treatment or prophylaxis of a subject with prostate cancer or a related condition or with the symptoms of prostate cancer, said method comprising the administration to said subject of a symptom-ameliorating effective amount of one or more of ingenol-3-angelate, 20-deoxy-ingenol-3-angelate and/or 20-O-acetyl-ingenol-3-angelate or derivative thereof or a pharmaceutically acceptable salt of these or a chemical fraction or plant extract comprising same.
82 . A method for the treatment or prophylaxis of prostate cancer or a related cancer in a subject, said method comprising the simultaneous or sequential administration to said subject of a symptom-ameliorating effective amount of a chemical agent derived from a plant of the Euphorbiaceae family together with a therapeutic protocol or a symptom-ameliorating effective amount of another chemical agent or a physical agent.
83 . (amended) Use of a chemical agent or derivative or chemical analog thereof as represented by any one of the present Formulae (I) to (V) or (VI) in the manufacture of a medicament for treatment and/or prophylaxis of prostate cancer or a related condition in a subject.
84 . A chemical agent derived from a plant of the Euphorbiaceae family coupled to a targeting agent.
85 . A chemical agent according to claim 84 wherein said agent prior to coupling is a compound of any of formulae (I)-(V) or (VI).
86 . A chemical agent according to claim 85 wherein said chemical agent is jatrophane.
87 . A chemical agent according to claim 86 wherein the chemical agent is jatrophane of conformation 2.
88 . A chemical agent according to claim 85 wherein said chemical agent prior to coupling is 5,8,9,10,14-pentaacetoxy-3-benzoyloxy-15-hydroxypepluane (pepluane) or a derivative thereof or a pharmaceutically acceptable salt of these.
89 . A chemical agent according to claim 88 wherein said derivative is an ester derivative.
90 . A chemical agent according to claim 85 wherein said chemical agent prior to coupling is 2,3,5,7,15-pentaacetoxy-9-nicotinoyloxy- 14-oxojatropha-6(17),11E-diene (jatrophane 1) or a derivative thereof or a pharmaceutically acceptable salt of these.
91 . A chemical agent according to claim 90 wherein said derivative is an ester derivative.
92 . A chemical agent according to claim 85 wherein said chemical agent prior to coupling is 2,5,7,8,9,14-hexaacetoxy-3-benzoyloxy-15-hydroxy-j atropha-6(17), 11E-diene (jatrophane 2) or a derivative thereof or a pharmaceutically acceptable salt of these.
93 . A chemical agent according to claim 92 wherein said derivative is an ester derivative.
94 . A chemical agent according to claim 85 wherein said chemical agent prior to coupling is 2,5,1 4 -triacetoxy-3-benzoyloxy-8,15-dihydroxy-7-isobutyroyloxy-9-nicotinoyloxyjatropha-6(17), 11E-diene (jatrophane 3) or a derivative thereof or a pharmaceutically acceptable salt of these.
95 . A cheinical agent according to claim 94 wherein said derivative is an ester derivative.
96 . A chemical agent according to claim 85 wherein said chemical agent prior to coupling is 2,5,9,14-tetraacetoxy-3-benzoyloxy-8,15-dihydroxy-7-isobutyroyloxy-jatropha-6(17), 11E-diene) ((jatrophane 4) or a derivative thereof or a pharmaceutically acceptable salt of these.
97 . A chemical agent according to claim 96 wherein said derivative is an ester derivative.
98 . A chemical agent according to claim 85 wherein said chemical agent prior to coupling is 2,5,7,14-tetraacetoxy-3-benzoyloxy-8,15-dihydroxy-9-nicotinoyloxy-jatropha-6(17), 11E-diene (jatrophane 5) or a derivative thereof or a pharmaceutically acceptable salt of these.
99 . A chemical agent according to claim 98 wherein said derivative is an ester derivative.
100 . A chemical agent according to claim 85 wherein said chemical agent prior to coupling is 2,5,7,9,14-pentaacetoxy-3-benzoyloxy-8,15-dihydroxyjatropha-6(17), 1E-diene (jatrophane 6) or a derivative thereof or a pharmaceutically acceptable salt of these.
101 . A chemical agent according to claim 100 wherein said derivative is an ester derivative.
102 . A chemical agent according to claim 85 wherein said chemical agent prior to coupling is 20-O-acetyl-ingenol-3-angelate or a derivative thereof or a pharmaceutically acceptable salt of these.
103 . A chemcial agent according to claim 102 wherein said derivative is an ester derivative.
104 . A chemical agent according to any one of claims 84 to 103 wherein said chemical agent is provided in the form of a composition comprising a pharmaceutically- or cosmetically-acceptable carrier.
105 . A chemical agent according to any one of claims 84 to 103 wherein the targeting agent is a bone-seeking agent.
106 . A chemical agent according to claim 105 wherein the bone-seeking agent is bisphosphonate.
107 . A chemical agent according to claim 106 wherein the bisphosphonate is methylene disphosphonate.
108 . A chemical agent according to any one of claims 84 to 103 wherein the targeting agent is an antibody.
109 . A chemical agent according to claim 108 wherein the targeting agent is an antibody to a prostate-specific tumor marker.
110 . A chemical agent according to claim 108 wherein the marker is prostate- specific antigen (PSA), prostate-specific membrane antigen (PMSA) or PSA receptor.
111 . A chemical agent according to claim 108 wherein the antibody is specific to a component of the immune system.
112 . A chemical agent according to claim 111 wherein the immune system component is a dendritic cell, B- or T-cell.Join the waitlist — get patent alerts
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