초록

The present invention relates to platinum complex chemotherapeutic compounds having the generic structure: wherein n is 0 or 1 and, preferably, one of R1, R2, R3 or R8 is a -(linker)-polymer group that may contain up to four additional platinum chelates.

대표청구항 ▼

What is claimed: 1. A compound having the chemical structure: wherein: n is 0 or 1; Pt is in a +2 or a +4 oxidation state; wherein; R1 and R2 are independently selected from the group consisting of: ═O; H; —C(O)OH; -(1C-6C)alkyl-C(O)OH; —C(O)O−R+; wherein: R+ is sel

What is claimed: 1. A compound having the chemical structure: wherein: n is 0 or 1; Pt is in a +2 or a +4 oxidation state; wherein; R1 and R2 are independently selected from the group consisting of: ═O; H; —C(O)OH; -(1C-6C)alkyl-C(O)OH; —C(O)O−R+; wherein: R+ is selected from the group consisting of Na+ and K+; provided that: when R2 is ═O, R1 is not ═O; R3 is selected from the group consisting of: —R9; -(1C-6C)alkyl-R9; —S(O)2R11; R9 is -(linker)-R10, wherein: -(linker) is  wherein: a is 2-50; b is 0 or 1; R10 is selected from the group consisting of: hydrogen; and, a natural, semi-synthetic or synthetic backbone polymer; R11 is selected from the group consisting of: —R9; -(1C-6C)alkyl-R9; R4 and R5 are independently selected from the group consisting of: ammonia; a primary, secondary or tertiary (1C-6C)alkyl amine; a (3C-8C)cycloalkyl amine; an aryl amine; a nitrogen heteroaryl; a nitrogen heteroalicyclic; an aminomethyl nitrogen heteroalicyclic; or, together, as R4—R5: a 1,2-, 1,3-, 1,4- or 1,5-diamino (2C-8C)alkane; a 1,2- or 1,4- diamino (3C-8C)cycloalkane; a 1,1- or 1,2-di(aminomethyl) (3C-8C)cycloalkane; a 1,1- or 1,2-di(aminomethyl) heteroalicyclic; a di(nitrogen heteroaryl); and a methylene di(nitrogen heteroaryl); if Pt is in the +2 oxidation state (Pt(II)), R6 and R7 do not exist; and, if Pt is in the +4 oxidation state (Pt(IV)), R6 and R7 are independently selected from the group consisting of —OH, H2O, Cl and (1C-6C)alkylC(O)O—. 2. A compound having the chemical structure: wherein: n is 0 or 1; Pt is in a +2 or a +4 oxidation state; R3 is selected from the group consisting of: —R9; -(1C-6C)alkyl-R9; R9 is -(linker)-R10, wherein: -(linker) is  wherein: a is 2-50; b is 0 or 1; R10 is selected from the group consisting of: hydrogen; and, a natural, semi-synthetic or synthetic backbone polymer; R4 and R5 are independently selected from the group consisting of: ammonia; a primary, secondary or tertiary (1C-6C)alkyl amine; a (3C-8C)cycloalkyl amine; an aryl amine; a nitrogen heteroaryl; a nitrogen heteroalicyclic; an aminomethyl nitrogen heteroalicyclic; or, together, as R4—R5: a 1,2-, 1,3-, 1,4- or 1,5-diamino (2C-8C)alkane; a 1,2- or 1,4-diamino (3C-8C)cycloalkane; a 1,1- or 1,2-di(aminomethyl) (3C-8C)cycloalkane; a 1,1- or 1,2-di(aminomethyl) heteroalicyclic; a di(nitrogen heteroaryl); and a methylene di(nitrogen heteroaryl); if Pt is in the +2 oxidation state (Pt(II)), R6 and R7 do not exist; and, if Pt is in the +4 oxidation state (Pt(IV)), R6 and R7 are independently selected from the group consisting of —OH, H2O, Cl and (1C-6C)alkylC(O)O—. 3. The compound of claims 1 or 2, wherein a is 2, 3, or 4. 4. The compound of claims 1 or 2, wherein at least one amino acid is glycine. 5. The compound of claims 1 or 2, wherein the amino acid is independently selected from glycine, leucine, or phenylalanine. 6. The compound of claims 1 or 2, wherein linker is selected from -G-G-, -G-G-G-, -G-G-G-G-, or -G-F-L-G-. 7. The compound of claims 1 or 2, wherein the polymer is poly(N-2-(hydroxypropoyl)methylacrylamide-co-methacrylamide. 8. The compound of claims 1 or 2, wherein R4 and R5 are taken together to form a 1,2- or 1,4-diamino (3C-8C)cycloalkane. 9. The compound of claim 8, wherein R4 and R5 are taken together and form 1R,2R-diaminocyclohexane. 10. The compound of claim 1 wherein the compound has the chemical structure: 11. The compound of claim 10 wherein the compound has the chemical structure: 12. The compound of claim 2 wherein the compound has the chemical structure: 13. The compound of claim 12, wherein the compound has the chemical structure: 14. The compound of claims 1 or 2, wherein the compound is selected from the group: p(HPMA)-GFLG-Ama-Pt=DACH; p(HPMA)-GG-Ama-Pt=DACH; p(HPMA)-GFLG-Asp=Pt=DACH; p(HPMA)-GG-Asp=Pt=DACH; p(HPMA)-GG-C3-Sulf-Ama=Pt=DACH; p(HPMA)-GG-C3-Sulf-Asp=Pt=DACH; p(HPMA)-GFLG-C3-Sulf-Ama=Pt=DACH; p(HPMA)-GFLG-C3-Sulf-Asp=Pt=DACH; p(HPMA)-GGGG-Ama=Pt=DACH; p(HPMA)-GGGG-Asp=Pt=DACH; or p(HPMA)-GGG-Ama=Pt=DACH wherein: p(HPMA) is poly(N-2-(hydroxypropyl)methylacrylamide-co-methacrylamide; G is glycine; F is phenylalanine; L is leucine; C3 is propylene; Sulf is sulfonyl; Ama is amidomalonate; Asp is aspartate; Pt is in the +2 oxidative state; and DACH is 1R,2R-diaminocyclohexane. 15. A pharmaceutical composition comprising: a compound of any preceding claim and one or more pharmaceutically acceptable excipients.