Tubulin binding ligands and corresponding prodrug constructs

A compound of the structure:

• 6
• wherein
• R1 through R5 contain at least one phosphate ester (—OP(O)(O−M+)2) or phosphoramidate (—NHP(O)(O−M+)2) moiety where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), while the remaining of R1 through R5 are hydrogen atoms.

A compound of the structure:

• 7
• wherein
• R1 through R5 contain at least one phosphate ester (—OP(O)(O−M+)2) or phosphoramidate (—NHP(O)(O−M+)2) moiety where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), while the remaining of R1 through R5 are hydrogen atoms, and R7 is H, or an alkyl or branched alkyl.

A compound of the structure:

• 13
• wherein
• R1 through R5 contain at least one phosphate ester (—OP(O)(O−M+)2) or phosphoramidate (—NHP(O)(O−M+)2) moiety where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), while the remaining of R1 through R5 are hydrogen atoms.

A compound of the structure:

• 14
• wherein
• R1 through R5 contain at least one phosphate ester (—OP(O)(O−M+)2) or phosphoramidate (—NHP(O)(O−M+)2) moiety where M=an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), while the remaining of R1 through R5 are hydrogen atoms, and R7 is H, or an alkyl or branched alkyl.

A compound of the structure:

• 16
• wherein
• R1 through R6 contain at least two phosphate esters (—OP(O)(O−M+)2) or two phosphoramidates (—NHP(O)(O−M+)2) moieties where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl, or aryl substituent (the two R groups are the same or different). or R1 through R6 contain one phosphate ester and one phosphoramidate, while of the remaining R1 through R6 one is substituted with an alkoxy group and the rest hydrogen atoms.

A compound of the structure:

• 18
• wherein
• R1 through R5 contain at least one phosphate ester (—OP(O)(O−M+)2) or phosphoramidate (—NHP(O)(O−M+)2) moiety where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), while the remaining of R1 through R5 are hydrogen atoms.

A compound of the structure:

• 19
• wherein
• R1 through R5 contain at least one phosphate ester (—OP(O)(O−M+)2) or a phosphoramidate (—NHP(O)(O−M+)2) moiety where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), while the remaining of R1 through R5 are hydrogen atoms, and R7 is H, or an alkyl or branched alkyl.

A compound of the structure:

• 21
• wherein
• R1 through R5 contain at least one phosphate ester (—OP(O)(O−M+)2) or phosphoramidate (—NHP(O)(O−M+)2) moiety where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), while the remaining of R1 through R5 are hydrogen atoms.

A compound of the structure:

• 22
• wherein
• R1 through R5 contain at least one phosphate ester (—OP(O)(O−M+)2) or a phosphoramidate (—NHP(O)(O−M+)2) moiety where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), while the remaining of R1 through R5 are hydrogen atoms, and R7 is H, or an alkyl or branched alkyl.

A compound of the structure:

• 24
• wherein
• R1 through R5 contain at least two phosphate ester (—OP(O)(O−M+)2) or two phosphoramidate moieties (—NHP(O)(O−M+)2) where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), R1 through R6 contain one phosphate ester and one phosphoramidate, while the remaining of R1 through R6 one is a methoxy group (—OCH3) and the rest hydrogen atoms.

A compound of the structure:

• 35
• wherein
• R1 through R4 contain at least two phosphate esters (—OP(O)(O−M+)2) or two phosphoramidates moieties (—NHP(O)(O−M+)2) where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R chosen to be any appropriate alkyl, branched alkyl, benzyl, or aryl substituent (the two R groups are the same or different), or R1 through R4 contain one phosphate ester and one phosphoramidate, while of the remaining R1 through R4 one is a methoxy group (—OCH3) and one is a hydrogen atom.

A compound of the structure:

• 40
• wherein
• R1 through R4 contain at least two phosphate ester (—OP(O)(O−M+)2) or two phosphoramidate moieties (—NHP(O)(O−M+)2) where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), where R through R4 contain one phosphate ester and one phosphoramidate, while of the remaining R1 through R4 one is a methoxy group (—OCH3) and one is a hydrogen atom.

A compound of the structure:

• 42
• wherein
• R1 through R5 contain at least one phosphate esters (—OP(O)(O−M+)2) or a phosphoramidate (—NHP(O)(O−M+)2) moiety where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl, or aryl substituent (the two R groups are the same or different), while the remaining of R1 through R5 are hydrogen atoms.

A compound of the structure:

• 44
• wherein
• R1 through R6 contain at least two phosphate esters (—OP(O)(O−M+)2) or two phosphoramidates (—NHP(O)(O−M+)2) moieties where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl, or aryl substituent (the two R groups are the same or different), or R1 through R6 contain one phosphate ester and one phosphoramidate, while of the remaining R1 through R6 one is substituted with a methoxy group (—OCH3) and the rest hydrogen atoms.

A compound of the structure:

• 47
• wherein
• R1 contains a phosphate ester (—OP(O)(O−M+)2) or a phosphoramidate (—NHP(O)(O−M+)2) moiety where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), while R2 is H, alkyl, branched alkyl, aryl, (alkoxy aryl or phenolic aryl moieties), benzyl, alkoxy benzyl, phenolic benzyl or vinyl.

A compound of the structure:

• 49
• wherein
• R1 contains a phosphate ester (—OP(O)(O−M+)2) or a phosphoramidate (—NHP(O)(O−M+)2) moiety where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl, or aryl substituent (the two R groups are the same or different), while R2 is H, alkyl, branched alkyl, aryl, (alkoxy aryl or phenolic aryl moieties), benzyl, alkoxy benzyl, phenolic benzyl or vinyl.

A compound of the structure:

• 51
• wherein
• R1 through R5 contain at least one phosphate ester (—OP(O)(O−M+)2) or a phosphoramidate (—NHP(O)(O−M+)2) moiety where M=an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl, or aryl substituent (the two R groups are the same or different), while at least one of the remaining R1 through R5 are at least one branched or straight chain alkoxy group and the remaining R groups substituted with hydrogen atoms, and n is 1, 2, or 3.

A compound of the structure:

• 53
• wherein
• R1 through R5 contain at least one phosphate ester (—OP(O)(O−M+)2) or a phosphoramidate (—NHP(O)(O−M+)2) moiety where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), while the remaining of R1 through R5 are at least one branched or straight chain alkoxy group and the remaining R groups substituted with a hydrogen atom, and n is 1, 2, or 3.

A compound of the structure:

• 55
• wherein
• R1 through R5 contain at least two phosphate esters (—OP(O)(O−M+)2) or two phosphoramidates (—NHP(O)(O−M+)2) moieties where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl, or aryl substituent (the two R groups are the same or different), or R1 through R5 contain one phosphate ester and one phosphoramidate, while of the remaining R1 through R5 one is substituted with a methoxy group (—OCH3) and the rest hydrogen atoms, and n is 1, 2, or 3.

A compound of the structure:

• 57
• wherein
• R1 through R5 contain at least one phosphate esters (—OP(O)(O−M+)2) or phosphoramidate (—NHP(O)(O−M+)2) moiety where M is an alkali metal cation;
• or (—NHP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl, or aryl substituent (the two R groups are the same or different), while of the remaining of R1 through R5 are hydrogen atoms.

A compound of the structure:

• 59
• wherein
• R1 through R6 contain at least two phosphate ester (—OP(O)(O−M+)2) or two phosphoramidate (—NP(O)(O−M+)2) moieties where M is an alkali metal cation;
• or (—NP(O)(OR)2) where R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), or R1 through R6 contain one phosphate ester and one phosphoramidate, while of the remaining R1 through R6 one is a methoxy group (—OCH3) and the rest hydrogen atoms.