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US 6,686,345 B2Granted
DNA-cleaving antitumor agents
AssigneeResearch Development Foundation
InventorsSean Michael Kerwin, Wendi M. David
Life of this patent
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Abstract
A chemical composition and method of use of the composition is described. The chemical composition includes an aza-enediyne, aza-enyne allene, or an aza-diallene. These compound are preferably non-hydrolyzable, cationic compounds that bind to nucleic acids. In addition it is believed that these compounds may undergo chemical reactions in the presence of a nucleic acid to generate reactive intermediates that cleave nucleic acids.
Claims10
A chemical compound comprising an iminium ion of an aza-derivative having the structure:
- R4R3C═NR1R2
- wherein R1 is —CH2C≡CH and R4 is —C≡C—C6H5, —C≡C—C6H4(CF3), —C≡C—C6H4(OCH3), —C≡C—C6H3(OCH3)2, —C≡C—C6H2(OCH3)3, —C≡C—C6H5(Si(CH3)), or —C≡C—C6H5(Si(CH(CH3)2);
- wherein R2 is a substituted-ethynyl group having the structure —C≡C—R5, a substituted-allenyl group having the structure —CR5═C═CR6R7, a substituted-propargyl group having the structure —CR5R6—C≡C—R7, hydrogen, alkyl, phenyl, aryl, aryl (C1-C4) alkyl, or a heterocycle substituent;
- wherein in each instance R5, R6, and R7 are independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, alkyl carbonyl, alkoxy carbonyl, silyl, phenyl, aryl, aryl (C1-C4) alkyl, hydroxy alkyl, a substituted hydroxyalkyl, an alkyl carboxylic acid derivative, an alkenyl carboxylic acid derivative, a nucleic acid interactive compound, a phosphine oxide, a sulfoxide, a sulfone, a heterocycle substituent, a carbocyclic substituent, one or more aza-derivatives, or where R5, R6, and R7 can join with themselves or each other to form a 9-26 membered ring;
- and
- wherein R3 is —SR8, —NR8R9, or —CR8R9, wherein in each instance R8 and R9 are independently a hydrogen, alkyl, phenyl, aryl, aryl (C1-C4) alkyl, trifluoromethylsulfonyl, silyl, substituted-ethynyl, substituted-allenyl, substituted propargyl, a sugar, a C-glycoside, a nucleic acid interactive compound, or a heterocycle substituent;
- wherein R2 and R3 along with parent iminium combine to form a pyridinium ring;
- and
- wherein said compound is associated with a counter ion;
- or a pharmaceutical composition thereof.
7 more elements
An oligomeric chemical composition comprising a compound, the compound comprising at least two covalently coupled iminium ions of aza-derivatives, wherein the aza derivatives have the structure:
- R4R3C═NR1R2;
- wherein R1 is independently alkyl or R10 and R4 is a substituted-ethynyl group having the structure —C═C(R5), or a substituted-alkenyl group having the structure —CH═CR5R11;
- wherein R10 is a substituted ethynyl, substituted allenyl, or substituted propargyl;
- wherein in R11 is OR12, SR12, N3, alkyl, or aryl and R12 is hydrogen, alkyl, phenyl, aryl, or aryl (C1-C4) alkyl
- wherein R2 is a substituted-ethynyl group having the structure —C≡C—R5, a substituted-allenyl group having the structure —CR5═C═CR6R7, a substituted-propargyl group having the structure —CR5R6—C≡C—R7, hydrogen, alkyl, phenyl, aryl, aryl (C1-C4) alkyl, or a heterocycle substituent;
- wherein in each instance R5, R6, and R7 are independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, alkyl carbonyl, alkoxy carbonyl, silyl, phenyl, aryl, aryl (C1-C4) alkyl, hydroxy alkyl, a substituted hydroxyalkyl, an alkyl carboxylic acid derivative, an alkenyl carboxylic acid derivative, a nucleic acid interactive compound, a phosphine oxide, a sulfoxide, a sulfone, a heterocycle substituent, a carbocyclic substituent, one or more aza-derivatives, or where R5, R6, and R7 can join with themselves or each other to form a 9-26 membered ring;
- and
- wherein R3 is —SR8, —NR8R9, or —CR8R9 wherein in each instance R8 and R9 are independently a hydrogen, alkyl, phenyl, aryl, aryl (C1-C4) alkyl, trifluoromethylsulfonyl, silyl, substituted-ethynyl, substituted-allenyl, substituted propargyl, a sugar, a C-glycoside, a nucleic acid interactive compound, or a heterocycle substituent;
- wherein R2 and R3 along with parent iminium combine to form a substituted heterocyclic ring;
- and
- wherein said compound is associated with a counter ion;
- or a pharmaceutical composition thereof;
- and
- wherein at least two of said substituted heterocyclic rings are covalently linked through a linking group, said linking group comprising a substituted heterocyclic ring whereby none of R2, R3 or R5 comprise the linking group.
11 more elements
Dependencies are inferred from the claim text.