Synthesis and use of heterocyclic antibacterial agents

A compound having the formula:

• and pharmaceutically acceptable salts, solvates and esters thereof, wherein:
• T1 and T2 are each independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, cycloalkenyl, cycloalkyl, aralkyl, aralkenyl, aralkenyl, cycloalkenylalkyl, cycloalkenylalkenyl, cyclylalkyl, cyclylalkenyl, heteroaryl, heterocyclenyl, heterocyclyl, heteroaralkyl, heteroaralkenyl, heterocyclenylalkyl, heterocyclenylalkenyl, heterocyclylalkyl, and heterocyclylalkenyl, wherein each of said alkyl, alkenyl, alkynyl, aryl, cycloalkenyl, cycloalkyl, aralkyl, aralkenyl, aralkenyl, cycloalkenylalkyl, cycloalkenylalkenyl, cyclylalkyl, cyclylalkenyl, heteroaryl, heterocyclenyl, heterocyclyl, heteroaralkyl, heteroaralkenyl, heterocyclenylalkyl, heterocyclenylalkenyl, heterocyclylalkyl, and heterocyclylalkenyl can be unsubstituted or substituted with one or more moieties independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, cycloalkenyl, cycloalkyl, aralkyl, aralkenyl, cycloalkenylalkyl, cycloalkenylalkenyl, cycloalkylalkyl, cycloalkylalkenyl, —OH, O-aryl, O-cycloalkenyl, —O-cycloalkyl, —O-heteroaryl, —O-heterocyclenyl, —O-heterocyclyl, —O-alkyl, —O-alkenyl, —O-alkynyl, —O-aralkyl, —O-aralkenyl, —O-cycloalkenylalkyl, —O-cycloalkylalkyl, —SH, S-aryl, S-cycloalkenyl, —S-cycloalkyl, —S-heteroaryl, —S-heterocyclenyl, —S-heterocyclyl, —S-alkyl, —S-alkenyl, —S-alkynyl, —S-aralkyl, —S-aralkenyl, —S-cycloalkenylalkyl, —S-cycloalkylalkyl, —NH2, NH-aryl, NH-cycloalkenyl, —NH-cycloalkyl, —NH-heteroaryl, —NH-heterocyclenyl, —NH-heterocyclyl, —NH-alkyl, —NH-alkenyl, —NH-alkynyl, —NH-aralkyl, —NH-aralkenyl, —NH-cycloalkenylalkyl, —NH-cycloalkylalky, further wherein each of said alkyl, alkenyl, alkynyl, aryl, cycloalkenyl, cycloalkyl, aralkyl, aralkenyl, aralkenyl, cycloalkenylalkyl, cyclylalkyl, heteroaryl, heterocyclenyl, heterocyclyl, heteroaralkyl, heteroaralkenyl, heterocyclenylalkyl, and heterocyclylalkyl can be unsubstituted or independently substituted from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, cycloalkenyl, cycloalkyl, aralkyl, aralkenyl, cycloalkenylalkyl, and cycloalkylalkyl;
• or
• T1 and T2 together with the carbon to which they are attached form a ring selected from the group consisting of spirocyclyl, spirocycloalkenyl, spiroheterocyclyl, and spiroheterocyclenyl, wherein each of said spirocyclyl, spirocycloalkenyl, spiroheterocyclyl, and spiroheterocyclenyl can be unsubstituted or substituted with up to three moieties, independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, cycloalkenyl, cycloalkyl, aralkyl, aralkenyl, cycloalkenylalkyl, cycloalkylalkyl, —OH, O-aryl, O-cycloalkenyl, —O-cycloalkyl, —O-heteroaryl, —O-heterocyclenyl, —O-heterocyclyl, —O-alkyl, —O-alkenyl, —O-alkynyl, —O-aralkyl, —O-aralkenyl, —O-cycloalkenylalkyl, —O-cycloalkylalkyl, —SH, S-aryl, S-cycloalkenyl, —S-cycloalkyl, —S-heteroaryl, —S-heterocyclenyl, —S-heterocyclyl, —S-alkyl, —S-alkenyl, —S-alkynyl, —S-aralkyl, —S-aralkenyl, —S-cycloalkenylalkyl, —S-cycloalkylalkyl, —NH2, —NH-aryl, —NH-cycloalkenyl, —NH-cycloalkyl, —NH-heteroaryl, —NH-heterocyclenyl, —NH-heterocyclyl, —NH-alkyl, —NH-alkenyl, —NH-alkynyl, —NH-aralkyl, —NH-aralkenyl, —NH-cycloalkenylalkyl, and —NH-cycloalkylalkyl;
• X and Y are independently selected from the group consisting of —CR5R6, —C(O), —S(O)2, —C(NH)— and NR5, wherein each of R5 and R6 is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocyclenyl, heterocyclyl, aralkyl, aralkenyl, cycloalkenylalkyl, cycloalkylalkyl, heteroaralkyl, heterocyclenylalkyl and heterocyclylalkyl, where in each of said alkyl, alkenyl, alkynyl, aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocyclenyl, heterocyclyl, aralkyl, aralkenyl, cycloalkenylalkyl, cycloalkylalkyl, heteroaralkyl, heterocyclenylalkyl and heterocyclylalkyl can be unsubstituted or substituted with up to three moieties independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, cycloalkenyl, cycloalkyl, aralkyl, aralkenyl, cycloalkenylalkyl, and cycloalkylalkyl;
• E is C, CH, or N;
• is a six-membered ring selected from the group consisting of aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocyclenyl and heterocyclyl;
• A is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, spirocyclyl, spirocycloalkenyl, spiroheterocyclyl, spiroheterocyclenyl, aryl, aralkyl, aralkenyl, cycloalkenylalkyl, cycloalkylalkyl, heteroaryl, heterocyclenyl, heterocyclyl, heteroaralkyl, heterocyclenylalkyl, heterocyclylalkyl, halo, —C(O)R, —C(S)R and —C(NH)R, wherein each of said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, spirocyclyl, spirocycloalkenyl, spiroheterocyclyl, spiroheterocyclenyl, aryl, aralkyl, aralkenyl, cycloalkenylalkyl, cycloalkylalkyl, heteroaryl, heterocyclenyl, heterocyclyl, heteroaralkyl, heterocyclenylalkyl, heterocyclylalkyl, is unsubstituted or substituted with up to three moieties independently selected from the group consisting of halo, —OH, O-aryl, O-cycloalkenyl, —O-cycloalkyl, —O-heteroaryl, —O-heterocyclenyl, —O-heterocyclyl, —O-alkyl, —O-alkenyl, —O-alkynyl, —O-aralkyl, —O-aralkenyl, —O-cycloalkenylalkyl, —O-cycloalkylalkyl, —SH, S-aryl, S-cycloalkenyl, —S-cycloalkyl, —S-heteroaryl, —S-heterocyclenyl, —S-heterocyclyl, —S-alkyl, —S-alkenyl, —S-alkynyl, —S-aralkyl, —S-aralkenyl, —S-cycloalkenylalkyl, —S-cycloalkylalkyl, —NH2, —NH-aryl, —NH-cycloalkenyl, —NH-cycloalkyl, —NH-heteroaryl, —NH-heterocyclenyl, —NH-heterocyclyl, —NH-alkyl, —NH-alkenyl, —NH-alkynyl, —NH-aralkyl, —NH-aralkenyl, —NH-cycloalkenylalkyl, —NH-cycloalkylalkyl, aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocyclenyl, heterocyclyl, alkyl, alkenyl and alkynyl, wherein each of said aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocyclenyl, heterocyclyl, alkyl, alkenyl, alkynyl, O-aryl, O-cycloalkenyl, —O-cycloalkyl, —O-heteroaryl, —O-heterocyclenyl, —O-heterocyclyl, —O-alkyl, —O-alkenyl, —O-alkynyl, —O-aralkyl, —O-aralkenyl, —O-cycloalkenylalkyl, —O-cycloalkylalkyl, S-aryl, S-cycloalkenyl, —S-cycloalkyl, —S-heteroaryl, —S-heterocyclenyl, —S-heterocyclyl, —S-alkyl, —S-alkenyl, —S-alkynyl, —S-aralkyl, —S-aralkenyl, —S-cycloalkenylalkyl, —S-cycloalkylalkyl, —NH-aryl, —NH-cycloalkenyl, —NH-cycloalkyl, —NH-heteroaryl, —NH-heterocyclenyl, —NH-heterocyclyl, —NH-alkyl, —NH-alkenyl, —NH-alkynyl, —NH-aralkyl, —NH-aralkenyl, —NH-cycloalkenylalkyl, —NH-cycloalkylalkyl, aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocyclenyl, heterocyclyl, alkyl, alkenyl, alkynyl can be unsubstituted or substituted with up to three moieties independently selected from the group consisting of halo, —OH, O-aryl, O-cycloalkenyl, —O-cycloalkyl, —O-heteroaryl, —O-heterocyclenyl, —O-heterocyclyl, —O-alkyl, —O-alkenyl, —O-alkynyl, —O-aralkyl, —O-aralkenyl, —O-cycloalkenylalkyl, —O-cycloalkylalkyl, —SH, S-aryl, S-cycloalkenyl, —S-cycloalkyl, —S-heteroaryl, —S-heterocyclenyl, —S-heterocyclyl, —S-alkyl, —S-alkenyl, —S-alkynyl, —S-aralkyl, —S-aralkenyl, —S-cycloalkenylalkyl, and —S-cycloalkylalkyl, —NH2, —NH-aryl, —NH-cycloalkenyl, —NH-cycloalkyl, —NH-heteroaryl, —NH-heterocyclenyl, —NH-heterocyclyl, —NH-alkyl, —NH-alkenyl, —NH-alkynyl, —NH-aralkyl, —NH-aralkenyl, —NH-cycloalkenylalkyl, —NH-cycloalkylalkyl, aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocyclenyl, heterocyclyl, alkyl, alkenyl, alkynyl, wherein each of said O-aryl, O-cycloalkenyl, —O-cycloalkyl, —O-heteroaryl, —O-heterocyclenyl, —O-heterocyclyl, —O-alkyl, —O-alkenyl, —O-alkynyl, —O-aralkyl, —O-aralkenyl, —O-cycloalkenylalkyl, —O-cycloalkylalkyl, S-aryl, S-cycloalkenyl, —S-cycloalkyl, —S-heteroaryl, —S-heterocyclenyl, —S-heterocyclyl, —S-alkyl, —S-alkenyl, —S-alkynyl, —S-aralkyl, —S-aralkenyl, —S-cycloalkenylalkyl, —S-cycloalkylalkyl, —NH-aryl, —NH-cycloalkenyl, —NH-cycloalkyl, —NH-heteroaryl, —NH-heterocyclenyl, —NH-heterocyclyl, —NH-alkyl, —NH-alkenyl, —NH-alkynyl, —NH-aralkyl, —NH-aralkenyl, —NH-cycloalkenylalkyl, —NH-cycloalkylalkyl, aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocyclenyl, heterocyclyl, alkyl, alkenyl and alkynyl can be unsubstituted or substituted with one or more moieties independently selected from the group consisting of halo, —OH, O-aryl, O-cycloalkenyl, —O-cycloalkyl, —O-heteroaryl, —O-heterocyclenyl, —O-heterocyclyl, —O-alkyl, —O-alkenyl, —O-alkynyl, —O-aralkyl, —O-aralkenyl, —O-cycloalkenylalkyl, —O-cycloalkylalkyl, —SH, S-aryl, S-cycloalkenyl, —S-cycloalkyl, —S-heteroaryl, —S-heterocyclenyl, —S-heterocyclyl, —S-alkyl, —S-alkenyl, —S-alkynyl, —S-aralkyl, —S-aralkenyl, —S-cycloalkenylalkyl, —S-cycloalkylalkyl, —NH-aryl, —NH-cycloalkenyl, —NH-cycloalkyl, —NH-heteroaryl, —NH-heterocyclenyl, —NH-heterocyclyl, —NH-alkyl, —NH-alkenyl, —NH-alkynyl, —NH-aralkyl, —NH-aralkenyl, —NH-cycloalkenylalkyl, —NH-cycloalkylalkyl, aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocyclenyl, heterocyclyl, alkyl, alkenyl and alkynyl;
• R2 is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl and heterocyclenyl, wherein each of said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, and heterocyclenyl can be unsubstituted or substituted with up to three moieties independently selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, aryl, cycloalkenyl, cycloalkyl, aralkyl, aralkenyl, cycloalkenylalkyl, cycloalkylalkyl, —OH, O-aryl, O-cycloalkenyl, —O-cycloalkyl, —O-heteroaryl, —O-heterocyclenyl, —O-heterocyclyl, —O-alkyl, —O-alkenyl, —O-alkynyl, —O-aralkyl, —O-aralkenyl, —O-cycloalkenylalkyl, —O-cycloalkylalkyl, —SH, S-aryl, S-cycloalkenyl, —S-cycloalkyl, —S-heteroaryl, —S-heterocyclenyl, —S-heterocyclyl, —S-alkyl, —S-alkenyl, —S-alkynyl, —S-aralkyl, —S-aralkenyl, —S-cycloalkenylalkyl, —S-cycloalkylalkyl, —NH2, —NH-aryl, —NH-cycloalkenyl, —NH-cycloalkyl, —NH-heteroaryl, —NH-heterocyclenyl, —NH-heterocyclyl, —NH-alkyl, —NH-alkenyl, —NH-alkynyl, —NH-aralkyl, —NH-aralkenyl, —NH-cycloalkenylalkyl, and —NH-cycloalkylalky.