Patent ID: 8642535

Claim:
A polymyxin derivative of formula (I): wherein: A is a polymyxin ring moiety having the following formula: wherein R4 of the polymyxin ring moiety is an amino acid residue selected from the group consisting of lysine, hydroxylysine, ornithine, glutamate, aspartate, an α,γ-diamino-n-butyryl residue, diaminopropionic acid, threonine, cysteine and serine; R6 is an amino acid residue selected from the group consisting of D-phenylalanine, D-leucine and D-tryptophan; R7 is an amino acid residue selected from the group consisting of leucine, threonine, phenylalanine, isoleucine, serine, alanine, valine, norvaline, and tryptophan; R10 is an amino acid residue selected from the group consisting of leucine, threonine, serine, O-acetyl-threonine, O-propionyl-threonine and O-butyryl-threonine; and wherein R5, R8 and R9 are amino acid residues independently selected from the group consisting of an α,γ-diamino-n-butyryl residue, lysine, 2-amino-4-guanido butyric acid, an α-aminobutyryl residue, and threonine; D is R 12 —(C═O); R 12 —SO 2 —; R 12 —(C═NH)—; R 12 —NH—(C═S)—; R 12 —NH—(C═O)—; R 12 —NH—(C═NH)—;R 12 —O—(C═S)—; R 12 —O—(C═O); R 12 —P(O)O H—; R 12 —(C═S); or R 12′ , wherein R 12 and R 12′ are alkyl, cycloalkyl, alkenyl, alkynyl, aryl, or aryl alkyl, and wherein D has no more than 1 to 5 carbon atoms; m 1 , m 2 , and m 3 are each independently 0 or 1; Q 1 , Q 2 , and Q 3 are each independently CH 2 , C═O, or C═S; W 1 , W 2 , and W 3 are each independently NR 4 , O, or S; R 1′ , R 2′ , and R 3′ are each independently side chains of natural or unnatural amino acids, alkyl, alkenyl, alkyl, arylalkyl, aryl, alkoxy, alkoxycarbonyl, aryloxycarbonyl, alkylamino, or alkynyl; and R 4 is hydrogen or alkyl, and pharmaceutically acceptable prodrugs and salts thereof wherein said derivative has three positive charges at physiological pH; and provided that at least one of m 1 , m 2 , and m 3 are 1.