Macrocycles and Their Uses

A method of treating a bacterial infection, comprising:

• administering to a subject in need thereof a pharmaceutically acceptable amount of a compound of Formula III:
• or pharmaceutically acceptable salts thereof;
• wherein
• q is 1, or 2 and the fragment
• is selected from the group consisting of:
• or
• q is 0 and E-R1 is selected from the group consisting of:
• and
• R1 is selected from the group consisting of hydrogen, hydroxymethyl, and aminomethyl and R12:
• R2a is hydrogen, hydroxy or amino, or is selected from the group consisting of C1-8alkoxy, amino, mono- and di-C1-8alkylamino, C3-7cycloalkylC0-6alkoxy, each of which is substituted with hydroxy, oxo, halo, C1-8alkyl, haloC1-8alkyl, C1-8alkoxy, haloC1-8alkoxy, C3-7cycloalkylC0-6alkyl, COOH, NH2, mono- and di-C1-8alkylamino, tri-C1-8alkylammonium, heterocycleC0-6alkyl, heteroarylC0-6alkyl, or —(CH2—CH2—O—)n—R8;
• R3 is selected from R12, OR12, N(R12)2 or R13;
• R4 is selected from hydrogen, CO2R4a, C(O)N(R4a)2, OR3a, N(R3a)2, or C(R10)(R11)phenyl;
• R4a is independently selected at each occurrence from hydrogen, hydroxymethyl, aminomethyl or R12;
• R6 is hydrogen or C1-4alkyl;
• R7 is selected from the group consisting of H, OH, NH2, C1-8alkyl, C1-8alkoxy, and mono- and di-C1-8alkylamino;
• R7b is independently selected at each occurrence from the group consisting of H, C1-8alkyl and —(CH2—CH2—O—)n—R8;
• R8 is independently selected at each occurrence from the group consisting of H, C1-8alkyl and CH2CO2H;
• R10 is absent or hydrogen;
• R11 is oxo, OR4a, N(R4a)2, or ═NR4a;
• R12 is independently selected at each occurrence from the group consisting of
• R13 is independently selected from the group consisting of
• n is an integer of between 1-60,000 or is a mean of a plurality of integers having a value of between 1-60,000;
• and
• p is 0, 1, 2, 3, or 4.