Broad spectrum beta-lactamase inhibitors

A compound of Formula:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• R is an acylamino group:
• R1 and R2 are independently selected from hydrogen, halogen, a C1-C6 alkyl group, a C1-C6 alkoxy group, and an —S-alkyl, where the alkyl group is a C1-C6 alkyl;
• n is an integer ranging from 1 to 5;
• —Z— is absent or present and, if present, represents —O—(CH2)X—, —S—(CH2)X—, —CH2—(CH2)X—, —NR′—(CH2)X—, —SO—(CH2)X—, or —SO2—(CH2)X—, where x is 0 or 1;
• Y is O-C+ or OR3 where R3 is hydrogen, or an optionally substituted alkyl or aryl group and C+ is a pharmaceutically acceptable cation;
• R′ is hydrogen or a C1-C6 alkyl group;
• and
• M, which is in the cis or trans position with respect to R1, is selected from the group consisting of B, E, and F as follows:
• where:
• each R8 is independently selected from hydrogen, halogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C7-C19 aralkyl group, 3-7-member ring cyclic hydrocarbon group, 3-7-member ring heterocyclic group, C6-C10 aromatic group, 6-10-member ring heterocyclic aromatic group, C1-C6 alkoxy group, —S-alkyl where the alkyl group is a C1-C6 alkyl, —CO—R′, —CO2R′, —CO—N(R′)2, —N(R′)2, —NR′—CO—R′, and —NR′CO2—R′, wherein each R′ for R8 groups is independently selected from hydrogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C7-C19 aralkyl group, 3-7-member ring cyclic hydrocarbon group, 3-7-member ring heterocyclic group, a C6-C10 aromatic group and a 6-10-member ring heterocyclic aromatic group, wherein each of said groups is optionally substituted;
• each R10 is independently selected from the group consisting of —CH2—X, hydrogen, halogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C7-C19 aralkyl group, 3-7-member ring cyclic hydrocarbon group, 3-7-member ring heterocyclic group, C6-C10 aromatic group, 6-10-member ring heterocyclic aromatic group, C1-C6 alkoxy group, C1 C6 thioalkyl group S-alkyl, where the alkyl group is a C1-C6 alkyl, —CO—R′, —CO2-R′, —CO—N(R′)2;
• —N(R′)2, —NR′—CO—R′, and —NR—CO2—R′, wherein each R′ for R10 groups is independently selected from hydrogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C7-C19 aralkyl group, 3-7-member ring cyclic hydrocarbon group, 3-7-member ring heterocyclic group, C6-C10 aromatic group, and 6-10-member ring heterocyclic aromatic group, wherein each of said groups is optionally substituted;
• R12 is selected from the group consisting of X, hydrogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C7-C19 aralkyl group, 3-7-member ring cyclic hydrocarbon group, 3-7-member ring heterocyclic group, C6-C10 aromatic group, and 6-10-member ring heterocyclic aromatic group, C1-C6 alkoxy group, —S-alkyl group, where the alkyl group is a C1-C6 alkyl group, —CO—R′, —CO2R′, —CO—N(R′)2;
• —N(R′)2, —NR′—CO—R′, and —NR—CO2—R′, wherein each R′ for R12 groups is independently selected from hydrogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group C7-C19 aralkyl group, 3-7-member ring cyclic hydrocarbon group, 3-7-member ring heterocyclic group, C6-C10 aromatic group, and 6-10-member ring heterocyclic aromatic group, wherein each of said groups is optionally substituted;
• and
• R13 and R14 are independently selected from the group consisting of X, hydrogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C7-C19 aralkyl group, 3-7-member ring cyclic hydrocarbon group, 3-7-member ring heterocyclic group, C6-C10 aromatic group, and 6-10-member ring heterocyclic aromatic group, C1-C6 alkoxy group, —S-alkyl group, where the alkyl group is a C1-C6 alkyl group, —CO—R′, —CO2—R′, —CO—N(R′)2;
• —N(R′)2, —NR′—CO—R′, and —NR—CO2—R′, wherein each R′ for R13 and R14 groups is independently selected from hydrogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C7-C19 aralkyl group, 3-7-member ring cyclic hydrocarbon group, 3-7-member ring heterocyclic group, C6-C10 aromatic group, and 6-10-member ring heterocyclic aromatic group, wherein each of said groups is optionally substituted;
• wherein optional substitution is substitution with one or more groups selected from C1-C3 alkyl, C6-C12 aryl, C1-C3 haloalkyl, I, Cl, Br, F, —CN, —OH, C1-C3 alkoxy, —O-aryl, —O-benzyl, -phenoxy, —SH, —S-alkyl, where the alkyl is a C1-C6 alkyl, —S— phenyl, —S-benzyl, —NH2, —N(R16)2, where each R16 is C1-C3 alkyl, benzyl or phenyl;
• wherein X is a leaving group;
• wherein in structure B at least one R10 is —CH2—X, in structure E at least one R10 is —CH2—X, or R12 is X and in structure F one of R13 or R14 is X;
• and
• wherein the compound contains at least one M.