Antibacterial compounds and uses thereof
AssigneePinnacle Pharmaceuticals, Inc.
InventorsSidney Hecht, Jing-Zhen Deng, Larisa Dedkova
Life of this patent
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Abstract
The invention relates to antibacterial compounds and their use to treat bacterial infections. More particularly, the invention relates to substituted biphenyl compounds having antibacterial activity. The invention provides methods for treating bacterial infections using PBDEs that have not previously been used to treat bacterial infections. The invention further provides novel PBDEs that are useful in such methods.
Claims27
A method for preventing or treating a bacterial infection comprising administering to a mammal potentially or actually having a bacterial infection a compound having the formula I:
- wherein R1 and R2 are each independently hydrogen, alkyl or heteroalkyl moieties having 1 to 4 carbon atoms, aryl, cycloalkyl moieties having 3 to 6 carbon atoms, heteroaryl or a polyhydroxylated tetrahydofuran or a tetrahydropyran, any of which may be substituted or unsubstituted;
- X1 and X2 represent a hydrogen or halogen;
- Y is oxygen, sulfur, sulfonyl, sulfenyl, selenium, carbonyl, alkylamino (—NR—) where R is selected from hydrogen, an alkyl or heteroalkyl moiety having of 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms or heteroaryl.
A method for preventing or treating a bacterial infection comprising administering to a mammal potentially or actually having a bacterial infection an antibacterial compound having the formula II:
- wherein R1 and R2 are each independently hydrogen, an alkyl or heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms, heteroaryl or a polyhydroxylated tetrahydofuran or a tetrahydropyran, any of which may be substituted or unsubstituted;
- Z1 and Z2, are each independently 1-3 hydrogen, bromine, chlorine, fluorine or hydroxyl groups;
- Y is oxygen, sulfur, sulfonyl, sulfenyl, selenium, carbonyl, alkylamino (—NR—)—CH2—O—, —CH2—S—, —CH2NHR— where R is selected from hydrogen, alkyl or a heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms or heteroaryl.
A method for preventing or treating a bacterial infection comprising administering to a mammal potentially or actually having a bacterial infection an antibacterial compound having the formula III:
- wherein R1 and R2 are each independently hydrogen, an alkyl or heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms, heteroaryl or a polyhydroxylated tetrahydofuran or a tetrahydropyran, any of which may be substituted or unsubstituted;
- Z1 and Z2 are each independently 1-3 hydrogen, bromine, chlorine, fluorine or hydroxyl groups;
- Y is oxygen, sulfur, sulfonyl, sulfenyl, selenium, carbonyl, alkylamino (—NR—)—CH2—O—, —CH2—S—, —CH2NHR— where R is selected from hydrogen, an alkyl or heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms, or heteroaryl.
A method for preventing or treating a bacterial infection comprising administering to a mammal potentially or actually having a bacterial infection an antibacterial compound having the formula IV:
- wherein R1 and R2 are each independently hydrogen, an alkyl or heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms, heteroaryl or a polyhydroxylated tetrahydofuran or a tetrahydropyran, any of which may be substituted or unsubstituted;
- Z1 and Z2, independent of one another, are selected from 1-3 hydrogen, bromine, chlorine, fluorine or hydroxyl groups;
- Y is oxygen, sulfur, sulfonyl, sulfenyl, selenium, carbonyl, alkylamino (—NR—)—CH2—O—, —CH2—S—, —CH2NHR— where R is selected from hydrogen, an alkyl or heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms, or heteroaryl.
A method for preventing or treating a bacterial infection comprising administering to a mammal potentially or actually having a bacterial infection an antibacterial compound having the formula V:
- wherein R1 and R2 are each independently hydrogen, an alkyl or heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms, heteroaryl or a polyhydroxylated tetrahydofuran or a tetrahydropyran, any of which may be substituted or unsubstituted;
- Z1 and Z2, independent of one another, are selected from 1-3 hydrogen, bromine, chlorine, fluorine or hydroxyl groups;
- Y is oxygen, sulfur, sulfonyl, sulfenyl, selenium, carbonyl, alkylamino (—NR—) where R is selected from hydrogen, an alkyl or heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms, or heteroaryl;
- and each of W1 and W2 is independently nitrogen or —NO—.
A method for preventing or treating a bacterial infection comprising administering to a mammal potentially or actually having a bacterial infection an antibacterial compound having a structure selected from the group consisting of
- wherein when the compound is JD-P-I-157-4, the bacterium is not Bacillus atrophaeus.
An antibacterial compound having the formula I:
- wherein R1 and R2 are each independently hydrogen, alkyl or heteroalkyl moieties having 1 to 4 carbon atoms, aryl, cycloalkyl moieties having 3 to 6 carbon atoms, heteroaryl or a polyhydroxylated tetrahydofuran or a tetrahydropyran, any of which may be substituted or unsubstituted;
- X1 and X2 represent a hydrogen or halogen;
- Y is oxygen, sulfur, sulfonyl, sulfenyl, selenium, carbonyl, alkylamino (—NR—) where R is selected from hydrogen, an alkyl or heteroalkyl moiety having of 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms or heteroaryl, wherein when Y is O and R1 is H, then R2 is not Me;
- and wherein when Y is O and R2 is H, then R1 is not Me. In some embodiments at least one of R1 and R2 is other than hydrogen.
An antibacterial compound having the formula II:
- wherein R1 and R2 are each independently hydrogen, an alkyl or heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms, heteroaryl or a polyhydroxylated tetrahydofuran or a tetrahydropyran, any of which may be substituted or unsubstituted, wherein at least one of R1 and R2 is other than hydrogen;
- Z1 and Z2, are each independently 1-3 hydrogen, bromine, chlorine, fluorine or hydroxyl groups;
- Y is oxygen, sulfur, sulfonyl, sulfenyl, selenium, carbonyl, alkylamino (—NR—)—CH2—O—, —CH2—S—, —CH2NHR— where R is selected from hydrogen, alkyl or a heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms or heteroaryl.
An antibacterial compound having the formula III:
- wherein R1 and R2 are each independently hydrogen, an alkyl or heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms, heteroaryl or a polyhydroxylated tetrahydofuran or a tetrahydropyran, any of which may be substituted or unsubstituted;
- wherein at least one of R1 and R2 is other than hydrogen;
- Z1 and Z2 are each independently 1-3 hydrogen, bromine, chlorine, fluorine or hydroxyl groups;
- Y is oxygen, sulfur, sulfonyl, sulfenyl, selenium, carbonyl, alkylamino (—NR—)—CH2—O—, —CH2—S—, —CH2NHR— where R is selected from hydrogen, an alkyl or heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms, or heteroaryl;
- and wherein when Y is O R1 is not hydrogen.
An antibacterial compound having the formula IV:
- wherein R1 and R2 are each independently hydrogen, an alkyl or heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms, heteroaryl or a polyhydroxylated tetrahydofuran or a tetrahydropyran, any of which may be substituted or unsubstituted;
- wherein at least one of R1 and R2 is other than hydrogen;
- Z1 and Z2, independent of one another, are selected from 1-3 hydrogen, bromine, chlorine, fluorine or hydroxyl groups;
- Y is oxygen, sulfur, sulfonyl, sulfenyl, selenium, carbonyl, alkylamino (—NR—)—CH2—O—, —CH2—S—, —CH2NHR— where R is selected from hydrogen, an alkyl or heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms, or heteroaryl.
An antibacterial compound having the formula V:
- wherein R1 and R2 are each independently hydrogen, an alkyl or heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms, heteroaryl or a polyhydroxylated tetrahydofuran or a tetrahydropyran, any of which may be substituted or unsubstituted;
- wherein at least one of R1 and R2 is other than hydrogen;
- Z1 and Z2, independent of one another, are selected from 1-3 hydrogen, bromine, chlorine, fluorine or hydroxyl groups;
- Y is oxygen, sulfur, sulfonyl, sulfenyl, selenium, carbonyl, alkylamino (—NR—) where R is selected from hydrogen, an alkyl or heteroalkyl moiety having 1 to 4 carbon atoms, aryl, a cycloalkyl moiety having 3 to 6 carbon atoms, or heteroaryl;
- and each of W1 and W2 is independently nitrogen or —NO—.
An antibacterial compound having a structure selected from the group consisting of
Dependencies are inferred from the claim text.