Platinum complex, its preparation and therapeutic use

Abstract

A platinum complex comprises a chemical structure of Structure I:whereL1 and L2 are independently selected from electron donor ligands, including but not limited to halogen ligands, hydroxo ligands, carboxylato ligands, and alkoxido ligands;R1, R2 and R3 are each independently selected from a hydrogen atom, hydrocarbon group, or heterocyclic group;wherein the hydrocarbon group is selected from: alkyl, alkenyl, cycloalkyl, phenyl, and naphthyl which may optionally be substituted by at least one functional group selected from the group consisting of: hydroxy, halogen, alkoxy, alkoxycarbonyl, carboxy, amido, amino, nitro, cyano, carbamate, urea, sulfonyl, sulfenyl, phosphenyl, phosphinyl, sulfide, thioether, thioester, sugar moiety, cyclodextrin, or porphyrin ring; andthe heterocyclic group is selected from: pyridyl, piperidyl, azino, azolyl, imidazolyl, triazinyl, furyl or carbozolyl;or two adjacent R1, R2 and R3 groups form a heterocycle or a carbocycle with or without an intermediary hetero atom or intermediary hetero atoms.

1 . A platinum complex comprising a chemical structure of Structure I: 
       
         
           
           
               
               
           
         
         wherein 
         L 1  and L 2  are independently selected from electron donor ligands, including but not limited to halogen ligands, hydroxo ligands, carboxylato ligands, and alkoxido ligands; 
         R 3 , R 4 , R 5 , R 6 , R 7  and R 8  are each independently selected from the group consisting of a hydrogen atom, hydrocarbon group, or heterocyclic group; 
         wherein the hydrocarbon group is selected from the group consisting of: alkyl, alkenyl, cycloalkyl, phenyl, and naphthyl which may optionally be substituted by at least one functional group selected from the group consisting of: hydroxy, halogen, alkoxy, alkoxycarbonyl, carboxy, amido, amino, nitro, cyano, carbamate, urea, sulfonyl, sulfenyl, phosphenyl, phosphinyl, sulfide, thioether, thioester, sugar moiety, cyclodextrin, and porphyrin ring; and 
         the heterocyclic group is selected from the group consisting of: pyridyl, piperidyl, azino, azolyl, imidazolyl, triazinyl, furyl and carbozolyl; 
         or two adjacent R 3 , R 4 , R 5 , R 6 , R 7  and R 8  groups form a heterocycle or a carbocycle with or without an intermediary hetero atom or intermediary hetero atoms. 
       
     
     
         2 . A platinum complex as claimed in  claim 1 ; wherein the complex has a structure of Structure (II): 
       
         
           
           
               
               
           
         
         wherein 
         R 3 , R 4 , R 5 , R 6 , R 7  and R 8  are independently selected from a hydrogen atom, a substituted or unsubstituted linear or branched chain C1 to C5 alkyl group, a cycloalkyl group, a substituted or unsubstituted aryl group, or a heteroaryl group, optionally R 3  is identical to R 6 , R 4  is identical to R 7 , and R 5  is identical to R 8 ; 
         R 9  and R 10  are independently selected from a hydrogen atom, a substituted or unsubstituted linear or branched chain C1 to C5 alkyl group, a substituted or unsubstituted aryl group, or a carboxyl group; and 
         n is an electrical charge of the complex and is selected from zero, any positive integer or negative integer (optionally n is 0, or 2+); 
         wherein when substituted a group may be substituted with a halo group, —NH 2 , an amine substituted with one or two C1-C5 alkyl, a linear or branched chain C1 to C5 alkyl group, a C1 to C5 alkoxy group, a C1 to C5 acyl group or a C1 to C5 carboxyl group. 
       
     
     
         3 . A platinum complex as claimed in  claim 1 ; wherein R 3 , R 4 , R 6 , and R 7  are independently selected from: a substituted or unsubstituted aryl group, or a heteroaryl group. 
     
     
         4 . A platinum complex as claimed in  claim 1  wherein; R 3 , R 4 , R 6 , and R 7  are independently selected from: phenyl, tolyl, chlorophenyl, methoxyphenyl, and fluorophenyl. 
     
     
         5 . A platinum complex as claimed in  claim 1  wherein; R 5  and R 8  are independently selected from: an unsubstituted linear or branched chain C1 to C5 alkyl group, a cycloalkyl group, a substituted or unsubstituted aryl group, or a heteroaryl group. 
     
     
         6 . A platinum complex as claimed in  claim 1  wherein; R 5  and R 8  are independently selected from: a C4 to C8 cycloalkyl group, an unsubstituted aryl group, a heteroaryl group, and an aryl group substituted with a halo group, —NH 2 , an amine substituted with one or two C1 to C5 alkyl groups, a linear or branched chain C1 to C5 alkyl group, or a C1 to C5 alkoxy group. 
     
     
         7 . A platinum complex as claimed in  claim 1  wherein; R 5  and R 8  are independently selected from: ethyl, cyclohexyl, pyridyl, tolyl, chlorophenyl, fluorophenyl, N,N-dimethylaminophenyl, methoxy phenyl. 
     
     
         8 . A platinum complex as claimed in  claim 1  wherein, R 9  and R 10  are independently selected from: a linear chain C1 to C5 alkyl group; a C1 to C5 carboxyl group; an unsubstituted aryl group (preferably a C6 to C10 aryl group); and an aryl group (preferably a C6 to C10 aryl group) substituted with a branched or linear chain C1 to C5 alkyl group, a C1 to C5 acyl group; a C1 to C5 carboxyl group (optionally —C(O) 2 H). 
     
     
         9 . A platinum complex as claimed in  claim 8  wherein; R 9  and R 10  are independently selected from: methyl, phenyl, carboxypropyl, and carboxyphenyl. 
     
     
         10 . A platinum complex as claimed in  claim 9  wherein; R 9  and R 10  are independently selected from any one of the following groups:
 a methyl group, 
 
       
         
           
           
               
               
           
         
       
       or a phenyl group. 
     
     
         11 . A platinum complex as claimed in  claim 1  wherein; R 1  and R 2  are independently selected from any one of the following groups:
 a methyl group, 
 
       
         
           
           
               
               
           
         
       
       or a phenyl group;
 R 3 , R 4 , R 6  and R 7  are identical, and they are selected from any one of the following groups: 
 a phenyl group, 
 
       
         
           
           
               
               
           
         
         R 5  and R 8  are identical and are selected from any one of the following groups: 
         an ethyl group, 
       
       
         
           
           
               
               
           
         
       
     
     
         12 . A platinum complex as claimed in  claim 1  wherein; the complex has the structure of Structure II wherein:
 R 3 , R 4 , R 5 , R 6 , R 7  and R 8  are phenyl and R 9  and R 10  are methyl; 
 R 3 , R 4 , R 5 , R 6 , R 7  and R 8  are phenyl and R 9  and R 10  are 
 
       
         
           
           
               
               
           
         
         R 3 , R 4 , R 5 , R 6 , R 7  and R 8  are phenyl and R 9  and R 10  are 
       
       
         
           
           
               
               
           
         
         R 3 , R 4 , R 5 , R 6 , R 7  and R 8  are phenyl; R 9  is methyl, and R 10  are phenyl; and 
         R 3 , R 4 , R 5 , R 6 , R 7  and R 8  are phenyl; R 9  is phenyl, and R 10  is 
       
       
         
           
           
               
               
           
         
       
     
     
         13 . A platinum complex as claimed in  claim 1  wherein; the complex has the structure of Structure II: 
       
         
           
           
               
               
           
         
       
     
     
         14 . A platinum complex as claimed in  claim 1  wherein; the complex has the structure of Structure III wherein:
 R 3 , R 4 , R 6  and R 7  are phenyl and R 5  and R 8  are 
 
       
         
           
           
               
               
           
         
         R 3 , R 4 , R 5 , R 6 , R 7  and R 8  are 
       
       
         
           
           
               
               
           
         
         R 3 , R 4 , R 5 , R 6 , R 7  and R 8  are 
       
       
         
           
           
               
               
           
         
         R 3 , R 4 , R 6  and R 7  are phenyl and R 5  and R 8  are 
       
       
         
           
           
               
               
           
         
         R 3 , R 4 , R 6  and R 7  are phenyl and R 5  and R 8  are 
       
       
         
           
           
               
               
           
         
       
     
     
         15 . In embodiments the platinum complex is a complex having the structure of Structure IV: 
       
         
           
           
               
               
           
         
       
     
     
         16 . A platinum complex as claimed in  claim 1  wherein; wherein PR 6 R 7 R 8  and PR 3 R 4 R 5  are represented by phosphine ligands selected from the following ligands: 
       
         
           
           
               
               
           
         
       
     
     
         17 . A platinum complex as claimed in  claim 1  having a structure of Structure V: 
       
         
           
           
               
               
           
         
         wherein 
         p is the number of methylene groups, which may be 1, 2, 3, or 4; 
         X- and X′- are selected from anions, including but not limited to nitrogen (N)-containing anions, oxygen (O)-containing anions, phosphorous (P)-containing anions, sulfur (S)-containing anions, and halogen containing anions; 
         R 3 , R 4 , R 6  and R 7  are each independently selected from the group consisting of a hydrogen atom, hydrocarbon group, or heterocyclic group; hydrocarbon group including but not limited to alkyl, alkenyl, cycloalkyl, phenyl, and naphthyl which may optionally be substituted by at least one functional group selected from the group consisting of hydroxy, halogen, alkoxy, alkoxycarbonyl, carboxy, amido, amino, nitro, cyano, carbamate, urea, sulfonyl, sulfenyl, phosphenyl, phosphinyl, sulfide, thioether, thioester, sugar moiety, cyclodextrin, and porphyrin ring; heterocyclic group is selected from the group consisting of pyridyl, piperidyl, azino, azolyl, imidazolyl, triazinyl, furyl and carbazolyl; or adjacent R 3 , R 4 , R 6  and R 7  may form a heterocycle or a carbocycle with or without an intermediary hetero atom or intermediary hetero atoms. 
       
     
     
         18 . A platinum complex as claimed in  claim 17 ; wherein; R 3 , R 4 , R 6  and R 7  have a definition set out in  claim 1 . 
     
     
         19 . A platinum complex as claimed in  claim 17  wherein; R 3 , R 4 , R 6  and R 7  are phenyl. 
     
     
         20 . A platinum complex as claimed in  claim 17  wherein; complex has a structure selected from Structure VIa and VIb: 
       
         
           
           
               
               
           
         
       
     
     
         21 .- 29 . (canceled) 
     
     
         30 . A process for preparing a compound as claimed in  claim 1 ; including the step of reaction of [PtXX′YY′L 1 L 2 ] and corresponding phosphine ligands (PR 1 R 2 R 3 ): 
       
         
           
           
               
               
           
         
         wherein: 
         X, X, Y, and Y′ are selected from electron donor ligands, including but not limited to nitrogen (N)-containing ligands, oxygen (O)-containing ligands, phosphorous (P) containing ligands, sulfur (S)-containing ligands, and halogen containing ligands; 
         L 1  and L 2  are independently selected from electron donor ligands, including but not limited to halogen ligands, hydroxo ligands, carboxylato ligands and alkoxido ligands; 
         R 3 , R 4 , R 5 , R 6 , R 7  and R 8  are are each independently selected from the group consisting of a hydrogen atom, hydrocarbon group, or heterocyclic group; hydrocarbon group including but not limited to alkyl, alkenyl, cycloalkyl, phenyl, and naphthyl which may optionally be substituted by at least one functional group selected from the group consisting of 
         hydroxy, halogen, alkoxy, alkoxycarbonyl, carboxy, amido, amino, nitro, cyano, carbamate, urea, sulfonyl, sulfenyl, phosphenyl, phosphinyl, sulfide, thioether, thioester, sugar moiety, cyclodextrin, and porphyrin ring; heterocyclic group is selected from the group consisting of pyridyl, piperidyl, azino, azolyl, imidazolyl, triazinyl, furyl and carbazolyl; or adjacent R 1 , R 2 , and R 3  may form a heterocycle or a carbocycle with or without an intermediary hetero atom or intermediary hetero atoms. 
       
     
     
         31 . A process for preparing a compound as claimed in  claim 1 ; including the step of reaction of [PtXX′YY′L 1 L 2 ] and a corresponding chelating phosphine ligands: 
       
         
           
           
               
               
           
         
         wherein 
         n is the number of methylene groups, which may be 1, 2, 3, or 4; 
         X- and X′- are selected from anions, including but not limited to nitrogen (N)-containing anions, oxygen (O)-containing anions, phosphorous (P)-containing anions, sulfur (S)-containing anions, and halogen containing anions; 
         Y, and Y′ are selected from electron donor ligands, including but not limited to nitrogen (N)-containing ligands, oxygen (O)-containing ligands, phosphorous (P). containing ligands, sulfur (S)-containing ligands, and halogen containing ligands; 
         L 1  and L 2  are independently selected from electron donor ligands, including but not limited to halogen ligands, hydroxo ligands, carboxylato ligands and alkoxido ligands; 
         R 3 , R 4 , R 6  and R 7  each independently selected from the group consisting of a hydrogen atom, hydrocarbon group, or heterocyclic group; hydrocarbon group including but not limited to alkyl, alkenyl, cycloalkyl, phenyl, and naphthyl which may optionally be substituted by at least one functional group selected from the group consisting of hydroxy, halogen, alkoxy, alkoxycarbonyl, carboxy, amide, amino, nitre, cyano, carbamate, urea, sulfonyl, sulfenyl, phosphenyl, phosphinyl, sulfide, thioether, thioester, sugar moiety, cyclodextrin, and porphyrin ring; heterocyclic group is selected from the group consisting of pyridyl, piperidyl, azino, azolyl, imidazolyl, triazinyl, furyl and carbazolyl; or adjacent R 3 , R 4 , R 6  and R 7  may form a heterocycle or a carbocycle with or without an intermediary hetero atom or intermediary hetero atoms.