Macrocyclic analogs and methods of their use and preparation

A compound having the formula:

• wherein A is a C1-6 saturated or C2-6 unsaturated hydrocarbon skeleton, said skeleton being unsubstituted or having between 1 and 10 substituents, inclusive, independently selected from cyano, halo, azido, oxo, and Q1;
• each Q1 is independently selected from OR1, SR1, SO2R1, OSO2R1, NR2R1, NR2(CO)R1, NR2(CO)(CO)R1, NR4(CO)NR2R1, NR2(CO)OR1, (CO)OR1, O(CO)R1, (CO)NR2R1, and O(CO)NR2R1;
• each of R1, R2, R4, R5, and R6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C6-10 aryl, C6-10 haloaryl, C6-10 hydroxyaryl, C1-3 alkoxy-C6 aryl, C6-10 aryl-C1-6 alkyl, C1-6 alkyl-C6-10 aryl, C6-10 haloaryl-C1-6 alkyl, C1-6 alkyl-C6-10 haloaryl, (C1-3 alkoxy-C6 aryl)-C1-3 alkyl, C2-9 heterocyclic radical, C2-9 heterocyclic radical-C1-6 alkyl, C2-9 heteroaryl, and C2-9 heteroaryl-C1-6 alkyl;
• each of D and D′ is independently selected from R3 and OR3, wherein R3 is H, C1-3 alkyl, or C1-3 haloalkyl;
• n is 0 or 1;
• E is R5 or OR5;
• G is O, S, CH2, or NR6;
• each of J and J′ is independently H, C1-6 alkoxy, or C1-6 alkyl;
• or J and J′ taken together are ═CH2 or —O-(straight or branched C1-5alkylene)-O—;
• Q is C1-3 alkyl;
• T is ethylene or ethenylene, optionally substituted with (CO)OR7, where R7 is H or C1-6 alkyl;
• each of U and U′ is independently H, C1-6 alkoxy, or C1-6 alkyl;
• or U and U′ taken together are ═CH2 or —O-(straight or branched C1-5alkylene)-O—;
• X is H or C1-6 alkoxy;
• each of Y and Y′ is independently H or C1-6 alkoxy;
• or Y and Y′ taken together are ═O, ═CH2, or —O-(straight or branched C1-5alkylene)-O—;
• and
• each of Z and Z′ is independently H or C1-6 alkoxy;
• or Z and Z′ taken together are ═O, ═CH2, or —O-(straight or branched C1-5alkylene)-O—;
• or a pharmaceutically acceptable salt thereof.