Tubulin binding ligands and corresponding prodrug constructs
AssigneeBaylor University
InventorsKevin G. Pinney, Vani P. Mocharla, Zhi Chen, Charles M. Garner, Anjan Ghatak, James M. Dorsey
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Abstract
A diverse set of tubulin binding ligands have been discovered which are structurally characterized, in a general sense, by a semi-rigid molecular framework capable of maintaining aryl—aryl, pseudo pi stacking distances appropriate for molecular recognition of tubulin. In phenolic or amino form, these ligands may be further functionalized to prepare phosphate esters, phosphate salts, and phosphoramidates capable of demonstrating selective targeting and destruction of tumor cell vasculature.
Claims16
A compound of the structure:
A compound of the structure:
A compound of the structure:
A compound of the structure:
A compound of the structure:
A compound of the structure:
A compound of the structure:
A compound of the structure:
- wherein
- Y is either NH, S, or O, and R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), or a metal cation.
A compound of the structure:
- wherein
- Y is either NH, S, or O, and R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups are the same or different), or a metal cation.
A compound of the structure:
- wherein
- R1 through R4 contain at least two phenolic moieties (—OH) or or at least two amino groups (NH2, NHR, or NR6R7) where R6 and R7 are the same or different alkyl, branched alkyl, benzyl, or aryl substituent, or R1 through R4 contain one phenolic moiety and one amino moiety, while the remaining R1 through R4 one is a methoxy (—OCH3) and one is a hydrogen atom.
A compound of the structure:
- 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:
- wherein
- If R1 is —OH or —NH2 then R2 is H, and if R2 is —OH or —NH2 then R1 is H.
A compound of the structure:
- wherein
- Y is either NH, S, or O, and R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups may be the same or different), or a metal cation.
A compound of the structure:
- wherein
- Y is either NH, S, or O, and R is an alkyl, branched alkyl, benzyl or aryl substituent (the two R groups may be the same or different), or a metal cation.
A compound of the structure:
- wherein
- R1 through R4 contain at least two phenolic moieties (—OH) or at least two amino group (NH2, NHR, or NR6R7) where R6 and R7 are the same or different alkyl, branched alkyl, benzyl, or aryl substituents, where R1 through R4 contain one phenolic moiety and one amino moiety, while of the remaining R1 through R4 one is a methoxy group (—OCH3) and one is a hydrogen atom.
A compound of the structure:
- 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 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.
Dependencies are inferred from the claim text.