Adenylation Enzyme Inhibitors

An adenylating enzyme (AE) substrate analogue having the structure according to formula (I):

• wherein R′ represents hydrogen or a moiety represented by the formula
• and wherein
• X represents —NH— or —O—;
• and
• R represents a peptide, or R represents
• a peptide having the structure of formula (ii)
• wherein Ra# represents an amino acid side chain identical to the amino acid side chain of the amino acid at the corresponding position in a reference AE substrate peptide;
• and [PEPTIDE] represents a peptide chain having the amino acid sequence —[Pω-1-P3]-wherein P# represents an amino acid residue identical to the amino acid residue in the corresponding position in said reference AE substrate peptide, wherein the positions are defined relative to C-terminal amino acid position, P1 representing the C-terminal amino acid residue and Pω representing the N-terminal amino acid residue;
• an N-terminally truncated variant of said peptide having the structure of formula (ii), said N-terminally truncated variant comprising a number of amino acid residues of (1) equal to or higher than 1, (2) equal to or higher than 2, or (3) equal to or higher than 5;
• or
• a homologue of said peptide or N-terminally truncated variant thereof;
• or
• wherein
• X represents —NH— or —O—;
• and
• R represents a group having the structure of formula (iii)
• wherein R5 is an optionally substituted carboxylic acid, carboxylate ester or a carboxylic acid isostere;
• R1-R4 are independently selected from hydrogen, hydroxy, amino, halo, cyano, nitro, —CF3, —CHF2, —CH2F, trifluoromethoxy, azido, (C1-C6)alkoxy, (C1-C6)alkanoyloxy, (C1-C6)alkyl, (C2-C6)alkenyl and (C2-C6)alkynyl, with the proviso that (1) at least 2 of R1-R4 or (2) at least 3 of R1-R4 represent hydrogen;
• or
• wherein
• X represents —CH2—;
• and
• R represents a fatty acid tail remnant, or R represents a Cω-Cγ— aliphatic saturated or mono- or polyunsaturated carbon atom chain, identical to the Cω-Cγ— part of an AE substrate fatty acid, wherein the carbon atoms are designated relative to the fatty acid carboxylate group, Cα represents the carbon atom adjacent to the carboxylate carbon atom of the fatty acid and Cω represents the terminal carbon atom of the fatty acid tail.