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US 2009/0023669 A1Published application
Antibacterial Agents
AssigneeAlchemia Limited
InventorsWim Meutermans, Declan McKeveney, Johannes Zuegg, Rajaratnam Premraj, Craig Muldoon, Giang Thanh Le
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Abstract
The present invention, in one aspect, provides a method of inhibiting bacterial growth by contacting bacteria with an effective amount of at least one monosaccharide compound of formula (1) as described herein:
Claims24
1:
- A method of inhibiting bacterial growth comprising contacting bacteria with at least one monosaccharide compound of formula (1):
- wherein,
- n is 0 or 1;
- the ring may be of any configuration and the anomeric center may be of either the α or β configuration;
- R1 is selected from the group consisting of hydrogen;
- OZ;
- SZ;
- OPO2(OZ)Z;
- SO2N(Z)Q;
- S(═O)N(Z)Q;
- N-Het wherein N and Het combine to form a heterocycle which may be further substituted with U groups;
- and —N(Z)Y wherein:
- Y is selected from hydrogen, or the following, where G denotes the point of connection to the nitrogen atom in N(Y)Z;
- Q is selected from hydrogen or W;
- the groups W are independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, of 1 to 20 carbon atoms, each of which is optionally substituted, branched and/or linear;
- wherein W is optionally substituted by one or more substituents selected from the group consisting of OH, NO, NO2, NH2, N3, halogen, CF3, CHF2, CH2F, nitrile, alkoxy, aryloxy, amidine, guanidiniums, carboxylic acid, carboxylic acid ester, carboxylic acid amide, aryl, cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl, aminodialkyl, aminotrialkyl, aminoacyl, carbonyl, substituted or unsubstituted imine, sulfate, sulfonamide, phosphate, phosphoramide, hydrazide, hydroxamate, and hydroxamic acid;
- each occurrence of Z is independently selected from the group consisting of:
- hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, acyl, arylacyl, heteroarylaryl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, of 1 to 20 carbon atoms, each of which is optionally substituted, branched and/or linear;
- wherein Z is optionally substituted by one or more substituents selected from the group consisting of OH, NO, NO2, NH2, N3, halogen, CF3, CHF2, CH2F, nitrile, alkoxy, aryloxy, amidine, guanidiniums, carboxylic acid, carboxylic acid ester, carboxylic acid amide, aryl, cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl, aminodialkyl, aminotrialkyl, aminoacyl, carbonyl, substituted or unsubstituted imine, sulfate, sulfonamide, phosphate, phosphoramide, hydrazide, hydroxamate, and hydroxamic acid;
- or
- wherein each occurrence of U is independently selected from the group consisting of:
- OH, NO, NO2, NH2, N3, halogen, CF3, CHF2, CH2F, nitrile, alkoxy, aryloxy, amidine, guanidinium, carboxylic acid, carboxylic acid ester, carboxylic acid amide, aryl, cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl, aminodialkyl, aminotrialkyl, aminoacyl, carbonyl, substituted or unsubstituted imine, sulfate, sulfonamide, phosphate, phosphoramide, hydrazide, hydroxamate, hydroxamic acid;
- heteroaryloxy, aminoaryl, aminoheteroaryl, thioalkyl, thioaryl, thioheteroaryl, alkyl, alkenyl, alkynyl, acyl, arylacyl, and heteroarylaryl;
- of 1 to 20 carbon atoms, each of which is optionally substituted, branched and/or linear;
- and
- wherein
- the groups R2, R3, R4 and R5 are independently selected from OZ or N-Het, wherein N and Het combine to form a heterocycle which may be further substituted with U groups;
- or N(Z)Y or OPO2(OZ)Z, wherein the groups Z and Y are as defined above;
- and wherein only one of R4 and R5 may be hydroxyl.
26 more elements
2:
- The method according to claim 1 wherein the compound is selected from the group consisting of the gluco- or galacto- or allo-configuration.
3:
- The method according to claim 2 wherein any one of R1-R5 is N-Het.
4:
- The method according to claim 3 wherein the N-het heterocycle is a monocyclic or bicyclic ring of 4 to 10 membered ring structure.
5:
- The method according to claim 2 wherein any one of R2 and R4 is N-Het, and wherein the N-het heterocycle is a monocyclic or bicyclic ring of 4 to 10 membered ring structure.
6:
- The method according to claim 3, wherein the N-het heterocyclic ring includes triazoles, benzimidazoles, benzimidazolothione, benzimidazolone, imidazole, hydanthione, thiohydanthione and purine.
7:
- The method according to claim 1 wherein any one of R1—R5 is N-Het.
8:
- The method according to claim 7 wherein the N-Het heterocycle is a monocyclic or bicyclic ring of 4 to 10 membered ring structure.
9:
- The method according to claim 8 wherein any one of R2 and R4 is N-Het, wherein the N-Het heterocycle is a monocyclic or bicyclic ring of 4 to 10 membered ring structure.
(canceled)
11:
- The method according to claim 7, wherein the N-het heterocyclic ring is selected from the group consisting of triazoles, benzimidazoles, benzimidazolothione, benzimidazolone, imidazole, hydanthione, thiohydanthione and purine.
12:
- The method according to claim 7, wherein the N-het heterocyclic ring may be further substituted with U groups;
- wherein each occurrence of U is independently selected from the group consisting of:
- OH, NO, NO2, NH2, N3, halogen, CF3, CHF2, CH2F, nitrile, alkoxy, aryloxy, amidine, guanidinium, carboxylic acid, carboxylic acid ester, carboxylic acid amide, aryl, cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl, aminodialkyl, aminotrialkyl, aminoacyl, carbonyl, substituted or unsubstituted imine, sulfate, sulfonamide, phosphate, phosphoramide, hydrazide, hydroxamate, hydroxamic acid;
- heteroaryloxy, aminoaryl, aminoheteroaryl, thioalkyl, thioaryl, thioheteroaryl, alkyl, alkenyl, alkynyl, acyl, arylacyl, and heteroarylaryl;
- of 1 to 20 carbon atoms which is optionally substituted, branched and/or linear.
2 more elements
13:
- The method according to claim 12, wherein the N-het heterocyclic ring may be further substituted with U groups selected from the group consisting of substituted alkyl, aryl, carboxyl and amino.
14:
- The method according to claim 12, wherein the U group is selected from the group consisting of OH, NO, NO2, NH2, N3, halogen, CF3, CHF2, CH2F, nitrile, alkoxy, aryloxy, amidine, guanidinium, carboxylic acid, carboxylic acid ester, carboxylic acid amide, aryl, cycloalkyl, heteroalkyl, heteroaryl, primary, secondary or tertiary amines, aminoacyl, carbonyl and substituted or unsubstituted imine.
15:
- The method according to claim, wherein in each occurrence Z is independently selected from the group consisting of:
- hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, acyl, arylacyl, heteroarylaryl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, of 1 to 20 carbon atoms which is optionally substituted, branched and/or linear.
16:
- The method according to claim 1, wherein the substituents are selected from the group consisting of OH, NO, NO2, NH2, N3, halogen, CF3, CHF2, CH2F, nitrile, alkoxy, aryloxy, amidine, guanidiniums, carboxylic acid, carboxylic acid ester, carboxylic acid amide, aryl, cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl, aminodialkyl, aminotrialkyl, aminoacyl, carbonyl, substituted or unsubstituted imine, sulfate, sulfonamide, phosphate, phosphoramide, hydrazide, hydroxamate, and hydroxamic acid.
17:
- The method according to claim 7, wherein the compound of formula I is selected from any one of the following:
18:
- A pharmaceutical composition comprising a compound of formula (1) selected from the group consisting of
- tautomers, esters, solvates, or pharmaceutically acceptable salts thereof, and a pharmaceutically acceptable carrier.
19:
- The method of claim 1, wherein the bacteria is Gram-positive bacteria.
20:
- The method of claim 1, wherein the bacteria is selected from the group consisting of an Escherichia bacteria, a Staphylococcus bacteria, Micrococcus bacteria, an Enterococcus bacteria, and a Streptococcus bacteria.
21:
- The method of claim 1, wherein said contacting comprises administering an effective amount of a compound of formula (1), to a subject in need of such treatment.
22:
- The method of claim 20, wherein the Staphylococcus bacteria is a methicillin resistant Staphylococci.
23:
- The method of claim 20, wherein the Staphylococcus bacteria is selected from the group consisting of Staphylococcus aureus and Staphylococcus aureus MRSA.
24:
- The method of claim 20, wherein the Enterococcus bacteria is a Vancomycin resistant Enterococci.
Dependencies are inferred from the claim text.