Compounds for treating bacterial infections
OwnerGad Glaser, Jehoshua Katzhendler +5inventors
InventorsGad Glaser, Jehoshua Katzhendler, Rolf Hilgenfeld, Roee Vidavski, Ezequiel Wexselblatt, Tamar Prez-Menahemov, Ilana Kaspy
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Abstract
The present invention relates to a novel class of guanine nucleotide analogs which inhibit RelA and Relseq synthetic activity and which possess anti-bacterial activity. The present invention also relates to pharmaceutical compositions that include such compounds, and to methods of use of such compounds or compositions for combating bacteria and treating bacterial infections.
Claims27
-41. (canceled)
A compound represented by the structure of formula (I):
- wherein:
- A and B are independently selected from the group consisting of:
- (a) —H;
- (b) —OR2;
- (c)
- (d)
- (e) —NR4R5;
- (f) N3;
- (g)
- (h)
- and
- (i)
- or A and B together represent a moiety selected from:
- (a)
- (b)
- and
- (c)
- Y is CH2 or O;
- Z is selected from the group consisting of:
- (a) OH;
- (b)
- (c)
- (d)
- (e)
- and
- (f)
- R1 is H, —COR10 or an amino protecting group;
- R2 is H, C1-C4 alkyl or a silyl hydroxyl protecting group;
- R3 is selected from the group consisting of:
- (a) —H;
- (b) —OH;
- (c)
- (d)
- (e)
- (f)
- and
- (g)
- R4 and R5 are independently H, C1-C4 alkyl or an amino protecting group;
- R6 and R7 are independently selected from the group consisting of:
- (a) —H;
- (b) C1-C4 alkyl;
- (c) an amino protecting group;
- and
- (d)
- R8 and R9 are independently selected from the group consisting of:
- (a) H;
- (b) CH3;
- (c) unsubstituted or substituted aryl, heteroaryl, cycloalkyl or heterocyclyl;
- and
- (d) —(CH2)p—COOH;
- R10 is H or a C1-C4 alkyl;
- m, n and p are each independently selected from 0, 1, 2, 3, 4, 5 and 6;
- AA represents an amino acid side chain;
- with the proviso that:
- (a) when Y is O;
- Z is OH and R1 is H:
- (i) A and B are not both H or OH or
- (ii) when one of A and B is H, the other one is not OH;
- (iii) when one of A and B is OH, the other one is not OCH3;
- (iv) when A is
- B is not H or OH;
- (v) when B is
- A is not OH;
- (vi) when A is
- then B is not H or OH;
- (vii) when B is
- then A is not OH;
- (viii) A and B together are not
- (ix) when A is NH2, B is not OH;
- and
- (x) when A is N3, B is not H;
- (b) when Y is CH2;
- Z is OH and R1 is H:
- (i) when one of A and B is
- the other is not OH;
- (ii) A and B together are not
- (iii) A and B are not both OH;
- (iv) when A is OH, B is not H;
- and
- (v) when B is OH, A is not OCH3;
- including salts, hydrates, solvates, polymorphs, optical isomers, geometrical isomers, enantiomers, diastereomers, complexes and mixtures thereof.
An anti-bacterial pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I-a), and a pharmaceutically acceptable carrier or excipient
- wherein:
- A and B are independently selected from the group consisting of:
- (a) —H;
- (b) —OR2;
- (c)
- (d)
- (e) —NR4R5;
- (f) N3;
- (g)
- (h)
- and
- (i)
- or A and B together represent a moiety selected from:
- (a)
- (b)
- and
- (c)
- Y is CH2 or O;
- Z is selected from the group consisting of:
- (a) OH;
- (b)
- (c)
- (d)
- (e)
- and
- (f)
- R1 is H or —COR16;
- R2 is H, C1-C4 alkyl or a hydroxyl protecting group;
- R3 is selected from the group consisting of:
- (a) —H;
- (b) —OH;
- (c)
- (d)
- (e)
- (f)
- and
- (g)
- R4 and R5 are independently H, C1-C4 alkyl or an amino protecting group;
- R6 and R7 are independently selected from the group consisting of:
- (a) —H;
- (b) C1-C4 alkyl;
- and
- (c)
- R8 and R9 are independently selected from the group consisting of:
- (a) H;
- (b) C1-C4 alkyl;
- (c) unsubstituted or substituted aryl, heteroaryl, cycloalkyl or heterocyclyl;
- and
- (d) —(CH2)p—COOH
- R10 is a C1-C4 alkyl;
- m, n and p are each independently selected from 0, 1, 2, 3, 4, 5 and 6;
- and
- AA represents an amino acid side chain;
- with the proviso that when Y is O;
- Z is OH, R1 is H and A is
- B is not OH;
- including salts, hydrates, solvates, polymorphs, optical isomers, geometrical isomers, enantiomers, diastereomers, complexes and mixtures thereof.
The composition according to claim 12, wherein the compound is selected from the group consisting of:
- wherein Y is CH2 or O;
- X is H or OH;
- and
- R3a is selected from the group consisting of:
- (a)
- (b)
- (c)
- (d)
- and
- (e)
Dependencies are inferred from the claim text.