Aminothiazoles and their uses

A compound of formula VII:

• or a pharmaceutically acceptable salt thereof, including the pyridine N-oxide thereof;
• wherein
• R1 is —Z—CO2H and -A-Z—CO2H;
• R1a is hydrogen, —Z—CO2H, and -A-Z—CO2H, wherein if R1a is hydrogen, then the Z residue of R1 is substituted by at least two CO2H groups;
• or
• R1 and R1a, taken in combination, form a saturated, partially unsaturated or aromatic heterocycle having 4 to 7 ring atoms and having 0-3 additional ring heteroatoms selected from N, O and S, wherein the heterocycle is substituted by at least two residues independently selected from CO2H, —Z—CO2H, and -A-Z—CO2H;
• A is independently selected at each occurrence from the group consisting of a —C(O)—, —C(O)O—, —C(O)N(R8a)—, —S(O)2—, —S(O)—, —C(H)═N—, —S(O)2N(R8a)—, and —S(O)N(R8a)—;
• Z is C1-C10alkylene, C3-C8cycloalkylene, C3-C8heterocycloalkylene, phenylene, or 5-6 membered heteroarylene, each of which is optionally substituted with one or more groups independently selected from C1-C4alkyl, C1-C4alkoxy, hydroxy, amino, mono- and di-C1-C6alkylamino, C(O)OH, or halogen;
• R2 is hydrogen, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkoxyC0-6alkyl, C3-7cycloalkylC0-4-alkyl, arylC0-4alkyl, or a residue of the formula:
• R2a is selected from the group consisting of H, substituted or unsubstituted alkyl, OH, OR4a, OC(O)R4a, OC(O)N(R8a)2 and N(R8a)2;
• R2b is selected from the group consisting of absent, H and alkyl, or R2a and R2b may together form ═O or ═NH;
• R3 an R12 are each, independently, selected from the group consisting of H, halogen, OR4b, -A-J, and N(R8a)2;
• R4a is selected from the group consisting of H, and alkyl;
• R4b is selected from the group consisting of alkyl and —(CH2—CH2—O—)n—R9, wherein n is an integer of 1-500, 1,000, 2,000, 3,000, 4,000, 5,000, 10,000, 20,000, 30,000, 40,000, 50,000, or 60,000 or is a mean of a plurality of integers having a value of 1-500, 1,000, 2,000, 3,000, 4,000, 5,000, 10,000, 20,000, 30,000, 40,000, 50,000, or 60,000;
• R5 is selected from the group consisting of H, alkyl, and R4b;
• J is selected from the group consisting of H, F, O-alkyl, N(R8a)2, N+(R8a)3, N(R8a)C(O)alkyl, CO2H, C(═O)N(R8a)2, CO2-alkyl, P(O)(OH)2, P(O)(O-alkyl)2, and a substituted nitrogen-containing heterocycle;
• R8a is absent, or selected from the group consisting of H, -(alkyl)-, -(cycloalkyl)-, C(alkyl)2-J, —R4b, wherein R8a can also cyclize with the atom to which R8a is bonded to form a 3, 4, 5, 6 or 7-membered ring that is aromatic or non-aromatic and may contain one or more heteroatoms, wherein the ring may be further substituted one or more times with substitutents that are the same or different;
• and
• R9 is selected from the group consisting of H, alkyl and CH2CO2H.