Polymyxin derivatives as antimicrobial compounds
The present invention relates to antimicrobial compounds and their uses, and in particular to peptide antibiotics which may be used in the treatment of bacterial infections such as Gram-negative bacterial infections, particularly those caused by multidrug-resistant (MDR) pathogens.
1. A compound of formula (IIb):
wherein:
R 1 is selected from hexanoyl, hepatanoyl, octanoyl, nonanoyl, decanoyl, dodecanoyl, 7 methyloctanoyl, S-5-methylheptanoyl, R-5-methylheptanoyl, S,R-5-methylheptanoyl (racemic mixture), 4-biphenylcarboxyl, 4-trifluoromethylbenzoyl, 4-ethylbenzoyl, 3,4-dichlorobenzoyl, 4-chlorobenzoyl, 3-chlorobenzoyl, pentafluorobenzoyl, 4-methylbenzoyl, 4-ethylphenylacetyl, phenylacetyl, 4-methylphenylacetyl, 4-trifluoromethylphenylacetyl, pentafluorophenylacetyl, 3,4-dichlorophenylacetyl, 4-chlorophenylacetyl, 3-chlorophenylacetyl, 2-chlorobenzoyl, 2-fluorobenzoyl, 2-methylbenzoyl, 2-chlorophenylacetyl, 2-fluorophenylacetyl, 2-methylphenylacetyl, 2,3-dichlorobenzoyl, 2,3-dimethylbenzoyl, 2,4-dichlorophenylacetyl, 2,4-dichlorobenzoyl, 2,4-dimethylbenzoyl, 2-chloro-4-methylbenzoyl, 2-chloro-4-trifluoromethylbenzoyl, 3-fluorobenzoyl, 3-methylbenzoyl, 3-trifuoromethylbenzoyl, 3,4-dimethylbenzoyl, 3-fluoro-4-methylbenzoyl, 4-chloro-3-methylbenzoyl, 3,4-dimethylphenylacetyl, 3-chloro-4-methylbenzoyl, 4-chloro-3-fluorobenzoyl, 3-fluoro-4-trifluoromethylbenzoyl, 3-chloro-4-fluorobenzoyl, 4-methyl-3-trifluoromethylbenzoyl, 3-methyl-4-trifluoromethylbenzoyl, 3-methyl-5-trifluoromethylbenzoyl, 3,5-dimethylbenzoyl, 3,5-dichlorobenzoyl, 3,5-bis(trifluoromethyl)benzoyl, 3-fluoro-5-trifluoromethylbenzoyl, 3-chloro-5-methylbenzoyl, 3-chloro-5-fluorobenzoyl, 2,4,6-trimethylbenzoyl, 2,4,6-trichlorobenzoyl, 2-chloro-4-fluorobenzoyl, 4-chloro-2-fluorobenzoyl, 3,4,5-trifluoromethylbenzoyl, 4-chloro-2-trifluoromethylbenzoyl, 2-fluoro-4-trifluoromethylbenzoyl, 3-biphenylcarboxyl, 4-chloro-biphenyl-4-carboxyl, 3-phenylproponyl, 4-phenylbutanoyl, 2,4-dichlorophenylsulfonyl, 4-chloro-3-trifluoromethylbenzoyl, 4-isopropylbenzoyl, 4-chloro-3-fluorobenzoyl, 3-chloro-4-trifluoromethylbenzoyl;
R 3 represents a side chain of an amino acid selected from leucine, phenylalanine, norleucine, norvaline or t-butylglycine;
R 4 represents a side chain of an amino acid selected from alanine, threonine, serine, valine, t-butylglycine, 2-aminobutyric acid or 2-aminoisobutyric acid; and
k and q are individually selected from 1, 2, or 3; or
pharmaceutically acceptable salts thereof.
2. The compound according to claim 1 , wherein R 4 represents the side chain of an amino acid selected from alanine, threonine, serine, 2-aminobutyric acid, or 2-aminoisobutyric acid.