Tricyclic gyrase inhibitors

A compound having the structure of Formula I

• or pharmaceutically suitable salts, esters, and prodrugs thereof,
• wherein
• L is O or S;
• R8 is H or an interacting substituent having a length of about 1 Å to about 5 Å from the carbon attachment point on the A Ring to the terminal atom in R8 and a width of about 3.3 Å or less;
• X, Y and Z are independently selected from the group consisting of N, CRX, CRY, and CRZ, provided that no more than two of X, Y and Z are N,
• wherein RX is H or an interacting substituent having a length of about 1 Å to about 2 Å from the carbon in CRX to the terminal atom in RX;
• wherein RY is H or an interacting substituent having a length of about 1 Å to about 3 Å from the carbon in CRY to the terminal atom in RY;
• wherein RZ is H or an interacting substituent having a length of about 1 Å to about 2 Å from the carbon in CRZ to the terminal atom in RZ;
• R2 is a 6-membered aryl or heteroaryl ring containing 0-3 O, S, or N heteroatoms, optionally substituted with 0-3 noninterfering substituents, wherein 2 adjacent noninterfering substituents on R2 may form one or more fused rings with the 6-membered aryl or heteroaryl ring;
• wherein the 6-membered aryl or heteroaryl ring of R2 has a CH at the positions immediately adjacent the position where R2 attaches to L;
• R4 is:
• H;
• an optionally substituted ORa;
• an optionally substituted secondary or tertiary amine attached to the C Ring through the secondary or tertiary amine N;
• or
• an optionally substituted 5-10 membered unsaturated cyclic or heterocyclic residue containing 0-3 N, O or S heteroatoms;
• wherein the optional substituent is 0-3 noninterfering substituents;
• wherein Ra is a 5-6 membered aryl or heteroaryl containing 0-3 O, S, or N heteroatoms optionally substituted with 0-3 noninterfering substituents;
• wherein the R4 substituent does not project greater than about 3 Å below the plane of the A, B and C Rings toward the GyrB/ParE binding pocket floor in the bound conformation;
• and
• wherein R4 does not sterically interfere with R2 or Z when the compound is in the bound conformation.