Quinolone analogs and methods related thereto

A compound of Formula (I),

• or a pharmaceutically acceptable salt or ester thereof;
• wherein indicates an optionally unsaturated bond;
• each of B, X, A or V is absent if Z1, Z2, Z3 and Z4, respectively, is N;
• and
• each of B, X, A and V is independently H, halo, azido, —CN, —CF3, —CONR1R2, —NR1R2, —SR2, —OR2, —R3, —W, -L-W, -L-N(R)—W0, A2 or A3, when each of Z1, Z2, Z3 and Z4, respectively, is C;
• Z is O, S, CR42, NR4CR4, CR4NR4, CR4, NR4 or N;
• each of Z1, Z2, Z3 and Z4 is independently C or N, provided any three N are non-adjacent;
• Z5 is C;
• or Z5 may be N when Z is N;
• Y is an optionally substituted 5-6 membered carbocyclic or heterocyclic ring;
• U1 is —C(=T)N(R)—, —C(=T)N(R)O—, —C(=T)-, —SO2N(R)—, —SO2N(R)N(R0)—, —SO2—, or —SO3—, where T is O, S, or NH;
• or U1 may be a bond when Z5 is N or U2 is H;
• U2 is H, or C3-C7 cycloalkyl, C1-C10 alkyl, C1-C10 heteroalkyl, C2-C10 alkenyl or C2-C10 heteroalkenyl group, each of which may be optionally substituted with one or more halogens, ═O, or an optionally substituted 3-7 membered carbocyclic or heterocyclic ring;
• or U2 is —W, -L-N(R)—W0, A2 or A3;
• in each —NR1R2, R1 and R2 together with N may form an optionally substituted azacyclic ring, optionally containing an additional heteroatom selected from N, O and S as a ring member;
• R1 is H or C1-C6 alkyl, optionally substituted with one or more halogens, or ═O;
• R2 is H, or C1-C10 alkyl, C1-C10 heteroalkyl, C2-C10 alkenyl, or C2-C10 heteroalkenyl, each of which may be optionally substituted with one or more halogens, ═O, or an optionally substituted 3-7 membered carbocyclic or heterocyclic ring;
• R3 is an optionally substituted C1-C10 alkyl, C2-C10 alkenyl, C5-C10 aryl, or C6-C12 arylalkyl, or a heteroform of one of these, each of which may be optionally substituted with one or more halogens, ═O, or an optionally substituted 3-6 membered carbocyclic or heterocyclic ring;
• each R4 is independently H, or C1-C6 alkyl;
• or R4 may be —W, -L-W or -L-N(R)—W0;
• each R and R0 is independently H or C1-C6 alkyl;
• L is a C1-C10 alkylene, C1-C10 heteroalkylene, C2-C10 alkenylene or C2-C10 heteroalkenylene linker, each of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, oxo (═O), or C1-C6 alkyl;
• W is an optionally substituted 4-7 membered azacyclic ring, optionally containing an additional heteroatom selected from N, O and S as a ring member;
• W0 is an optionally substituted 3-4 membered carbocyclic ring, or a C1-C6 alkyl group substituted with from 1 to 4 fluorine atoms;
• provided one of U2, V, A, X and B is a secondary amine A2 or a tertiary amine A3, wherein
• the secondary amine A2 is —NH—W0, and
• the tertiary amine A3 is a fully saturated and optionally substituted six-membered or seven-membered azacyclic ring optionally containing an additional heteroatom selected from O or S as a ring member, or the tertiary amine A3 is a partially unsaturated or aromatic optionally substituted five-membered azacyclic ring, optionally containing an additional heteroatom selected from N, O or S as a ring member;
• with the proviso that when Z1 is N, Z2 and Z4 are C, Z5 is C, U1 is —C(O)NH—, U2 is -L-W, and L is an ethylene linker, one of V, A, and X is independently an optionally substituted aryl, heteroaryl, or 7-membered azacyclic ring, optionally containing an additional heteroatom selected from N, O and S as a ring member, if W is pyrrolidin-1-yl, piperidin-1-yl or morpholin-1-yl.