Beta-lactam compounds and methods of use thereof

A compound to detect carbapenemases or microbial carbapenemase resistance, wherein the compound has the structure of Formulas Ia, Ib, Ic, Id or Ie, or salts thereof,

• (a) wherein A is a divalent group selected from —(CR4═CR5)m—, —(C≡C)n—, optionally substituted arylenes, optionally substituted heteroarylenes, and covalent adducts thereof, wherein the covalent adducts are conjugated systems and wherein m and n are positive integers;
• (b) wherein D is connected to A via a methylene bridge and comprises a chemical probe, wherein D comprises a luminescence probe, and the luminescence probe is selected from the group consisting of resorufin, fluorescein, Tokyo Green, coumarin, and luciferin;
• (c) wherein the beta-lactam ring of the compound can be hydrolyzed by one or more carbapenemases, thereby triggering intramolecular rearrangement to release D from the compound;
• (d) wherein R1, R2, R4, and R5 are independently:
• a hydrogen atom, a halogen atom, a sulfonic acid, an azide group, a cyanate group, an isocyanate group, a nitrate group, a nitrile group, an isonitrile group, a nitrosooxy group, a nitroso group, a nitro group, an aldehyde group, an acyl halide group, a carboxylic acid group, a carboxylate group, an optionally substituted alkyl group, an optionally substituted heteroalkyl group, an optionally substituted alkenyl group, an optionally substituted heteroalkenyl group, an optionally substituted alkynyl group, an optionally substituted heteroalkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group;
• a hydroxyl group optionally containing one substituent at the hydroxyl oxygen, wherein the substituent is an optionally substituted alkyl group, an optionally substituted heteroalkyl group, an optionally substituted alkenyl group, an optionally substituted heteroalkenyl group, an optionally substituted alkynyl group, an optionally substituted heteroalkynyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group;
• a thiol group optionally containing one substituent at the thiol sulfur, wherein the substituent is an optionally substituted alkyl group, an optionally substituted heteroalkyl group, an optionally substituted alkenyl group, an optionally substituted heteroalkenyl group, an optionally substituted alkynyl group, an optionally substituted heteroalkynyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group;
• a sulfonyl group containing an optionally substituted alkyl group, an optionally substituted heteroalkyl group, an optionally substituted alkenyl group, an optionally substituted heteroalkenyl group, an optionally substituted alkynyl group, an optionally substituted heteroalkynyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group;
• an amino group optionally containing one or two substituents at the amino nitrogen, wherein the substituents are optionally substituted alkyl groups, optionally substituted heteroalkyl groups, optionally substituted alkenyl groups, optionally substituted heteroalkenyl groups, optionally substituted alkynyl groups, optionally substituted heteroalkynyl groups, optionally substituted aryl groups, optionally substituted heteroaryl groups, or combinations thereof;
• an amide group optionally containing one or two substituents at the amide nitrogen, wherein the substituents are optionally substituted alkyl groups, optionally substituted heteroalkyl groups, optionally substituted alkenyl groups, optionally substituted heteroalkenyl groups, optionally substituted alkynyl groups, optionally substituted heteroalkynyl groups, optionally substituted aryl groups, optionally substituted heteroaryl groups, or combinations thereof;
• an azo group containing an optionally substituted alkyl group, an optionally substituted heteroalkyl group, an optionally substituted alkenyl group, an optionally substituted heteroalkenyl group, an optionally substituted alkynyl group, an optionally substituted heteroalkynyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group;
• an acyl group containing an optionally substituted alkyl group, an optionally substituted heteroalkyl group, an optionally substituted alkenyl group, an optionally substituted heteroalkenyl group, an optionally substituted alkynyl group, an optionally substituted heteroalkynyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group;
• an ester group containing an optionally substituted alkyl group, an optionally substituted heteroalkyl group, an optionally substituted alkenyl group, an optionally substituted heteroalkenyl group, an optionally substituted alkynyl group, an optionally substituted heteroalkynyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group;
• a carbonate ester group containing an optionally substituted alkyl group, an optionally substituted heteroalkyl group, an optionally substituted alkenyl group, an optionally substituted heteroalkenyl group, an optionally substituted alkynyl group, an optionally substituted heteroalkynyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group;
• an ether group containing an optionally substituted alkyl group, an optionally substituted heteroalkyl group, an optionally substituted alkenyl group, an optionally substituted heteroalkenyl group, an optionally substituted alkynyl group, an optionally substituted heteroalkynyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group;
• an aminooxy group optionally containing one or two substituents at the amino nitrogen, wherein the substituents are optionally substituted alkyl groups, optionally substituted heteroalkyl groups, optionally substituted alkenyl groups, optionally substituted heteroalkenyl groups, optionally substituted alkynyl groups, optionally substituted heteroalkynyl groups, optionally substituted aryl groups, optionally substituted heteroaryl groups, or combinations thereof;
• or
• a hydroxyamino group optionally containing one or two substituents, wherein the substituents are optionally substituted alkyl groups, optionally substituted heteroalkyl groups, optionally substituted alkenyl groups, optionally substituted heteroalkenyl groups, optionally substituted alkynyl groups, optionally substituted heteroalkynyl groups, optionally substituted aryl groups, optionally substituted heteroaryl groups, or combinations thereof;
• (e) wherein R3 is:
• a carboxylic acid or carboxylate;
• an ester group containing an optionally substituted alkyl group, an optionally substituted heteroalkyl group, an optionally substituted alkenyl group, an optionally substituted heteroalkenyl group, an optionally substituted alkynyl group, an optionally substituted heteroalkynyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group;
• an amide group optionally containing one or two substituents at the amide nitrogen, wherein the substituents are optionally substituted alkyl groups, optionally substituted heteroalkyl groups, optionally substituted alkenyl groups, optionally substituted heteroalkenyl groups, optionally substituted alkynyl groups, optionally substituted heteroalkynyl groups, optionally substituted aryl groups, optionally substituted heteroaryl groups, or combinations thereof;
• or
• a hydroxamate group optionally containing one or two substituents, wherein the substituents are optionally substituted alkyl groups, optionally substituted heteroalkyl groups, optionally substituted alkenyl groups, optionally substituted heteroalkenyl groups, optionally substituted alkynyl groups, optionally substituted heteroalkynyl groups, optionally substituted aryl groups, optionally substituted heteroaryl groups, or combinations thereof;
• (f) wherein R1, R2, R3, R4, and R5, and their substituents are optionally and independently substituted with one or more chemical groups, wherein each chemical group is independently:
• a halogen atom, an alkyl group, a heteroalkyl group, an alkenyl group, a heteroalkenyl group, an alkynyl group, a heteroalkynyl group, an aryl group, a heteroaryl group, —OH, —SH, —NH2, —N3, —OCN, —NCO, —ONO2, —CN, —NC, —ONO, —CONH2, —NO, —NO2, —ONH2, —SCN, —SNCS, —CF3, —CH2CF3, —CH2Cl, —CHCl2, —CH2NH2, —NHCOH, —CHO, —OOCl, —COF, —COBr, —COOH, —SO3H, —CH2SO2CH3, —PO3H2, —OPO3H2, —P(═O)(ORG1)(ORG2), —OP(═O)(ORG1)(ORG2), —BRG1(ORG2), —B(ORG1)(ORG2), or -GRG1 in which -G is —O—, —S—, —NRG2—, —C(═O)—, —S(═O)—, —SO2—, —C(═O)O—, —C(═O)NRG2—, —OC(═O)—, —NRG2C(═O)—, —OC(═O)O—, —OC(═O)NRG2—, —NRG2C(═O)O—, —NRG2C(═O)NRG3—, —C(═S)—, —C(═S)S—, —SC(═S)—, —SC(═S)S—, —C(═NRG2)—, —C(═NRG2)O—, —C(═NRG2)NRG3—, —OC(═NRG2)—, —NRG2C(═NRG3)—, —NRG2SO2—, —C(═NRG2)NRG3—, —OC(═NRG2)—, —NRG2C(═NRG3)—, —NRG2SO2—, —NRG2SO2NRG3—, —NRG2C(═S)—, —SC(═S)NRG2—, —NRG2C(═S)S—, —NRG2C(═S)NRG3—, —SC(═NRG2)—, —C(═S)NRG2—, —OC(═S)NRG2—, —NRG2C(═S)O—, —SC(═O)NRG2—, —NRG2C(═O)S—, —C(═O)S—, —SC(═O)—, —SC(═O)S—, —C(═S)O—, —OC(═S)—, —OC(═S)O—, —SO2NRG2—, —BRG2—, or —PRG2—,
• wherein each occurrence of RG1, RG2, and RG3 is, independently, a hydrogen atom, a halogen atom, an alkyl group, a heteroalkyl group, an alkenyl group, a heteroalkenyl group, an alkynyl group, a heteroalkynyl group, an aryl group, or a heteroaryl group.