# US 9,040,538 B2 · Pyrimidines as novel therapeutic agents

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- Number: US 9,040,538 B2
- Document ID: US9040538B2
- Status: Granted
- Kind: B2
- Application number: 12/784,975
- Filed: 2010-05-21
- Published: 2010-11-25
- Granted: 2015-05-26
- Earliest claimed: 2009-05-21
- Assignees: Universite Laval
- Applicants: Giorgio Attardo; Sasmita Tripathy; Martin Gagnon
- Inventors: Giorgio Attardo; Sasmita Tripathy; Martin Gagnon
- Web page: https://patentgrep.com/patent/US9040538B2

## CPC

- C07D 513/04: Ortho-condensed systems
- A61K 31/435: having six-membered rings with one nitrogen as the only ring hetero atom
- A61K 31/497: containing further heterocyclic rings
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07D 239/38: One sulfur atom
- C07D 239/47: One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
- C07D 239/56: One oxygen atom and one sulfur atom
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more hetero rings
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 403/14: containing three or more hetero rings
- C07D 409/12: linked by a chain containing hetero atoms as chain links
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 471/04: Ortho-condensed systems
- C07D 487/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention features compounds having the Formula (Ia) and (Ib) (e.g., a compound of any of Formulas ((Ia-2)-(Ia-21)), including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, pharmaceutically acceptable salts, and compositions thereof. The invention also features methods for treating or preventing pain (e.g., neuropathic pain), inflammation, or epilepsy in a patient by administering an effective amount of a compound of Formula (Ia) or (Ib). The invention also features a method for treating or preventing pain (e.g., neuropathic pain), inflammation, or epilepsy in a patient that includes administering to a patient in need thereof an effective amount of a compound of Formula (IIa) or (IIb) (e.g., a compound of any of Formulas ((IIa-2)-(IIa-6)). The compounds described herein (e.g., a compound of Formulas (Ia), (Ib), (IIa), or (IIb)) can also be used as anticonvulsants.

## Claims

### Claim 1

A compound having the structure of a formula selected from the group consisting of:
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R4, R6, and R8 are each, independently, absent —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2, and R5 and R7 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2, or R4 and R5, or R5 and R6, or R6 and R7, or R7 and R8, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle, provided that the resulting ring system is not unsubstituted imidazo[1,2-a]pyridine, 5- or 6-chloro-imidazo[1,2-a]pyridine, 8-substituted quinoline, 2- or 4-chloro-quinoline, or 4-hydroxy-1,3-quinazoline;
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle; and
Q2, Q4, and Q6 are each, independently, N, N+—O−, or C, wherein Q2, Q4, and Q6 are not simultaneously C;
wherein,
(a) when each of R5, R6, R7, and R8 is H, Q2 is N, and each of Q4 and Q6 is C, R3 is not —CF3, —C1-C3 alkyl, or difluorobenzyl,
(b) when each of R4, R5, R6, and R7 is H, Q6 is N, and each of Q2 and Q4 is C, R3 is not —CF3, —C1-C3 alkyl, or difluorobenzyl, and
(c) when each of R4, R5, R7, and R8 is H, Q4 is N, and each of Q2 and Q6 is C, R3 is not —CH3, —CH2CH2CH3, or difluorobenzyl;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R4, R5, R6, and R7 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2, or R4 and R5, or R5 and R6, or R6 and R7, together with the carbon atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle, provided that the resulting ring system is not 8-substituted quinoline or 4-chloro-quinoline; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle,
wherein, when each of R4, R5, R6, and R7 is H, R3 is not —CF3, —C1-C3 alkyl, or difluorobenzyl;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R4, R5, R6, and R8 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2, or R4 and R5, or R5 and R6, together with the carbon atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle, provided that the resulting ring system is not 8-substituted quinoline or 2- or 4-chloro-quinoline; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle,
wherein,
(a) when each of R5 and R6 is H, R4 is chloro, and R8 is H or chloro, R3 is not —CF3 or —C1-C3 alkyl, and
(b) when each of R4, R5, R6, and R8 is H, R3 is not —CF3 or —C1-C3 alkyl;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R4, R5, R7, and R8 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2, or R4 and R5, or R7 and R8, together with the carbon atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle, provided that the resulting ring system is not 8-substituted quinoline or 2- or 4-chloro-quinoline; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle,
wherein, when each of R4, R5, R7, and R8 is H, R3 is not —CH3, —CH2CH2CH3, or difluorobenzyl;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R4, R5, R6, and R7, are each, independently, absent, —H, -D, —OH, halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2, or R4 and R5, or R5 and R6, or R6 and R7, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle, provided that the resulting ring system is not unsubstituted imidazo[1,2-a]pyridine, 5- or 6-chloro-imidazo[1,2-a]pyridine, or substituted or unsubstituted benzimidazole;
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle; and
Q3, Q4, Q5, and Q6 are each, independently, N, N+—O−, or C;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R4 and R7, are each, independently, absent, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2, and R5 and R6 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2, or R4 and R5, or R5 and R6, or R6 and R7, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle;
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle; and
Q3 and Q6 are each, independently, N, N+—O−, or C;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R5, R6, and R7 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2, or R4 and R5, or R5 and R6, or R6 and R7, together with the carbon atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R5 is —H, —OH, —CN, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —C(O)N(Z)2, —C(O)OZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2;
R6 and R7 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or R5 and R6, or R6 and R7, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R4 is —H, —OH, —CN, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —C(O)N(Z)2, —C(O)OZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2;
R6, and R7 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or R6 and R7, together with the carbon atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R4 is —H, —OH, —CN, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —C(O)N(Z)2, —C(O)OZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2;
R5, and R7 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or R4 and R5, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic heterocycle; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R4, R5 and R7 are each, independently, —H, -D, —OH, halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or R4 and R5, together with the carbon atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle, provided that the resulting ring system is not unsubstituted imidazo[1,2-a]pyridine or 5- or 6-chloro-imidazo[1,2-a]pyridine; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R4 is —H, —OH, —CN, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —C(O)N(Z)2, —C(O)OZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2;
R5 and R6 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or R4 and R5, or R5 and R6, together with the carbon atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle wherein R5 is not —NO2 when R6 is —H, and provided that the resulting ring system is not substituted or unsubstituted benzimidazole, unsubstituted imidazo[1,2-a]pyridine, or 5- or 6-chloro-imidazo[1,2-a]pyridine; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R5 and R6 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2, or R5 and R6, together with the carbon atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R4 is —H, —OH, —CN, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —C(O)N(Z)2, —C(O)OZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2;
R5, R6, and R7 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or R5 and R6, or R6 and R7, together with the carbon atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a3- to 7-membered aromatic or non aromatic heterocycle;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R5 and R6 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or R5 and R6, together with the carbon atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle provided that the resulting ring system is not unsubstituted benzothiazole; and
each Z is, independently, —H, —C1-C6 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, alkynyl, or —CN;
R5 and R7 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R4 and R7 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R6 and R7 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or R6 and R7, together with the carbon atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R5 and R6 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or R5 and R6, together with the carbon atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle; and
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
R2 is —H, -D, —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R3 is —CF3, —C1-C5 alkyl, —C2-C5 alkenyl, —C2-C5 alkynyl, or —CN;
R5 and R7 are each, independently, —H, -D, —OH, -halogen, —CN, —NO2, —C1-C5 alkyl, —C3-C6 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —OZ, —N(Z)2, —C(NH)N(Z)2, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, or —NZC(NCN)N(Z)2; and
each Z is, independently, —H, —C1-C5 alkyl, —C3-C7 cycloalkyl, —C6 aryl, —C7-C9 arylalkyl, 3 to 7-membered aromatic or non aromatic heterocycle, —C2-C5 alkenyl, or —C2-C5 alkynyl, or two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle.

### Claim 2

A compound having the following structure:
and its tautomer
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
Q1 is —S—, —SO—, —SO2—, —CH2CH2—, —CH═CH—, —OCH2—, —SCH2—, —SOCH2—, or —SO2CH2—;
V is O, S, NH, or NZ, or N-terminal linked amino acid, or halogen when R1 is absent;
R1 is absent, —H, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, —(CH2)nOZ, —C(O)Z, —C(O)OZ, —C(O)NHZ, —C(O)N(Z)2, —(CR1AR1B)r2OPO(OZ)2, —(CR2AR2B)r3PO(OZ)2, or C-terminal linked amino acid;
each R1A, R1B, R2A, and R2B is, independently, H or C1-5 alkyl;
Z is either —H or —CH3;
each n is 1 or 2;
each r2 is an integer between 1-3;
each r3 is an integer between 0-2;
R2 is —H, -D, —OH, -halogen, —CN, —NO2, —SH, —CF3, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
R3 is —OH, -halogen, —CN, —NO2, —SH, —CF3, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
A1 and A2 are each, independently, —H, -D, -halogen, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, or —C7-C14 arylalkyl;
A3 is an aromatic heterocyclic ring selected from the group consisting of:
Q2, Q5, and Q6 are each, independently, N, N+—O−, or C;
Q3 and Q4 are each, independently, N, N+—O−, C, O, or S, wherein only one of Q3 and Q4 can be O or S;
wherein Q2, Q3, Q4, Q5, and Q6 simultaneously are C only if R4 and R5, R5 and R6, R6 and R7, or R7 and R8, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic heterocyclyl; and
R4, R5, R6, R7, and R8 are each, independently, absent, —H, -D, —OH, —O−, -halogen, —CN, —NO2, —SH, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, —PO(OZ)2, or R4 and R5, or R5 and R6, or R6 and R7, or R7 and R8, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle, provided that the resulting ring system is not substituted or unsubstituted benzimidazole, unsubstituted benzothiazole, unsubstituted imidazo[1,2-a]pyridine, 5- or 6-chloro-imidazo[1,2-a]pyridine, unsubstituted quinoline, 8-substituted quinoline, unsubstituted quinoxaline, 2- or 4-chloro-quinoline, or 4-hydroxy-1,3-quinazoline,
wherein when A3 is unsubstituted pyridine-2-yl, and A1 and A2 are each —H, R3 is not —OH, —CF3, —C1-C3 alkyl, phenyl, difluorobenzyl, or —NHC(O)CH3;
wherein when A3 is unsubstituted pyridine-4-yl, and A1 and A2 are each —H, R3 is not —OH, —CH3, CH2CH2CH3, or difluorobenzyl;
wherein when A3 is unsubstituted, 6-chloro, or 2,6-dichloro pyridine-3-yl, and A1 and A2 are each —H, R3 is not —OH, —CF3, —C1-C3 alkyl, phenyl, or —NHC(O)CH3;
wherein when A3 is substituted or unsubstituted pyrazol-1-yl, R3 is not —OH;
wherein A3 is not 4-NO2-imidazol-2-yl; and
provided that
(a) R1 is —(CH2)nOZ, —C(O)Z, —C(O)OZ, —C(O)NHZ, —C(O)N(Z)2, —(CR1AR1B)r2OPO(OZ)2, or —(CR2AR2B)r3PO(OZ)2;
(b) R2 is —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
c) R3 is —OZ, —C(NH)N(Z)2, O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2; or
(d) at least one of R4, R5, R6, R7, and R8 is —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2.

### Claim 3

A compound having the following structure
and its tautomer
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
Q1 is —S—, —SO—, —SO2—, —CH2CH2—, —CH═CH—, —OCH2—, —SCH2—, —SOCH2—, or —SO2CH2—;
V is O, S, NH, or NZ, or N-terminal linked amino acid, or halogen when R1 is absent;
R1 is absent, —H, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, —(CH2)nOZ, —C(O)Z, —C(O)OZ, —C(O)NHZ, —C(O)N(Z)2, —(CR1AR1B)r2OPO(OZ)2, —(CR2AR2B)r3PO(OZ)2, or C-terminal linked amino acid;
each R1A, R1B, R2A, and R2B is, independently, H or C1-5 alkyl;
each Z is, independently, —H, —C1-C8 alkyl, —C4-C12 alkcycloalkyl, —C3-C9 alkheterocyclyl, wherein the heterocyclyl is 3 to 9 membered, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —C2-C8 alkenyl, or —C2-C8 alkynyl, or two Z, together with the atom(s) to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
each n is 1 or 2;
each r2 is an integer between 1-3;
each r3 is an integer between 0-2;
R2 is —H, -D, —OH, -halogen, —CN, —NO2, —SH, —CF3, —C1-C3 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
R3 is —OH, -halogen, —CN, —NO2, —SH, —CF3, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
A1 and A2 are each, independently, —H, -D, -halogen, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, or —C7-C14 arylalkyl;
A3 is an aromatic heterocyclic ring selected from the group consisting of:
Q2, Q5, and Q6 are each, independently, N, N+—O−, or C;
Q3 and Q4 are each, independently, N, N+—O−,C, O, or S, wherein only one of Q3 and Q4 can be O or S;
wherein Q2, Q3, Q4, Q5, and Q6 simultaneously are C only if R4 and R5, R5 and R6, R6 and R7, or R7 and R8, together with the atoms to which each is attached, loin to form a 5- to 6-membered aromatic or non aromatic heterocyclyl; and
R4, R5, R6, R7, and R8 are each, independently, absent, —H, -D, —OH, —O−, -halogen, —CN, —NO2, —SH, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, —PO(OZ)2, or R4 and R5, or R5 and R6, or R6 and R7, or R7 and R8, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle provided that the resulting ring system is not substituted or unsubstituted benzimidazole, unsubstituted benzothiazole, unsubstituted imidazo[1,2-a]pyridine, 5- or 6-chloro-imidazo[1,2-a]pyridine, indole when R2 is C(O)OCH2CH3 unsubstituted quinoline, 8-substituted quinoline, unsubstituted quinoxaline, 2- or 4-chloro-quinoline, or 4-hydroxy-1,3-quinazoline,
wherein when A3 is unsubstituted pyridine-2-yl, and A1 and A2 are each —H, R3 is not —OH, —CF3, —C1-C3 alkyl, phenyl, difluorobenzyl, —NHC(O)furan, —NHC(O)CH3, or —NHC(O)CH2CH3;
wherein when A3 is unsubstituted pyridine-4-yl, and A1 and A2 are each —H, R3 is not —OH, —CH3, CH2CH2CH3, or difluorobenzyl;
wherein when A3 is unsubstituted, 6-chloro, or 2,6-dichloro pyridine-3-yl, and A1 and A2 are each —H, R3 is not —OH, —CF3, —C1-C3 alkyl, phenyl, —C(O)OCH2CH3, or —NHC(O)CH3;
wherein when A3 is substituted or unsubstituted pyrazol-1-yl, R3 is not —OH;
wherein A3 is not 4-NO2-imidazol-2-yl; and
provided that
(a) R1 is —C(O)N(Z)2, —(CR1AR1B)r2OPO(OZ)2, or —(CR2AR2B)r3PO(OZ)2;
(b) R2 is —N(Z)2, —C(NH)N(Z)2, —OC(O)N(Z)2, —C(O)N(Z)2, —S(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
c) R3 is —C(NH)N(Z)2, —OC(O)N(Z)2, —C(O)N(Z)2, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2; or
(d) at least one of R4, R5, R6, R7, and R8 is —N(Z)2, —C(NH)N(Z)2, —OC(O)N(Z)2, —C(O)N(Z)2, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2; and
provided that two Z, together with the atom to which each is attached, join to form a 5-, 6-, or 7-membered non aromatic heterocycle.

### Claim 4

A compound having the following structure:
and its tautomer
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
Q1 is —S—, —SO—, —SO2—, —CH2CH2—, —CH═CH—, —OCH2—, —SCH2—, —SOCH2—, or —SO2CH2—;
V is O, S, NH, or NZ, or N-terminal linked amino acid, or halogen when R1 is absent;
R1 is absent, —H, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, —(CH2)nOZ, —C(O)Z, —C(O)OZ, —C(O)NHZ, —C(O)N(Z)2, —(CR1AR1B)r2OPO(OZ)2, —(CR2AR2B)r3PO(OZ)2, or C-terminal linked amino acid;
each R1A, R1B, R2A, and R2B is, independently, H or C1-5 alkyl;
each Z is, independently, —H, —C1-C8 alkyl, —C4-C12alkcycloalkyl, —C3-C9 alkheterocyclyl, wherein the heterocyclyl is 3 to 9 membered, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —C2-C8 alkenyl, or —C2-C8 alkynyl, or two Z, together with the atom(s) to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
each n is 1 or 2;
each r2 is an integer between 1-3;
each r3 is an integer between 0-2;
R2 is —H, -D, —OH, -halogen, —CN, —NO2, —SH, —CF3, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
R3 is —OH, -halogen, —CN, —NO2, —SH, —CF3, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
A1 and A2 are each, independently, —H, -D, -halogen, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, or —C7-C14 arylalkyl;
A3 is an aromatic heterocyclic ring selected from the group consisting of:
Q2, Q5, and Q6 are each, independently, N, N+—O−, or C;
Q3 and Q4 are each, independently, N, N+—O−, C, O, or S, wherein only one of Q3 and Q4 can be O or S;
wherein Q2, Q3, Q4, Q5, and Q6 simultaneously are C only if R4 and R5, R5 and R6, R6 and R7, or R7 and R8, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic heterocyclyl; and
R4, R5, R6, R7, and R8 are each, independently, absent, —H, -D, —OH, —O−, -halogen, —CN, —NO2, —SH, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, —PO(OZ)2, or R4 and R5, or R5 and R6, or R6 and R7, or R7 and R8, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle provided that the resulting ring system is not substituted or unsubstituted benzimidazole, unsubstituted benzothiazole, unsubstituted imidazo[1,2-a]pyridine, 5- or 6-chloro-imidazo[1,2-a]pyridine, indole when R2 is C(O)OCH2CH3 unsubstituted quinoline, 8-substituted quinoline, unsubstituted quinoxaline, 2- or 4-chloro-quinoline, or 4-hydroxy-1,3-quinazoline,
wherein when A3 is unsubstituted pyridine-2-yl, and A1 and A2 are each —H, R3 is not —OH, —CF3, —C1-C3 alkyl, phenyl, difluorobenzyl, —NHC(O)furan, —NHC(O)CH3, or —NHC(O)CH2CH3;
wherein when A3 is unsubstituted pyridine-4-yl, and A1 and A2 are each —H, R3 is not —OH, —CH3, —CH2CH2CH3, or difluorobenzyl;
wherein when A3 is unsubstituted, 6-chloro, or 2,6-dichloro pyridine-3-yl, and A1 and A2 are each —H, R3 is not —OH, —CF3, —C1-C3 alkyl, phenyl, —C(O)OCH2CH3, or —NHC(O)CH3;
wherein when A3 is substituted or unsubstituted pyrazol-1-yl, R3 is not —OH;
wherein A3 is not 4-NO2-imidazol-2-yl; and
provided that
(a) R1 is —C(O)N(Z)2, —(CR1AR1B)r2OPO(OZ)2, or —(CR2AR2B)r3PO(OZ)2;
(b) R2 is —N(Z)2, —C(NH)N(Z)2, —OC(O)N(Z)2, —C(O)N(Z)2, —S(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
c) R3 is —C(NH)N(Z)2, —OC(O)N(Z)2, —C(O)N(Z)2, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2; or
(d) at least one of R4, R5, R6, R7, and R8 is —N(Z)2, —C(NH)N(Z)2, —OC(O)N(Z)2, —C(O)N(Z)2, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2; and
provided that two Z, together with the atom to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle, wherein the heterocycle is substituted with any of the substituent groups described herein for R4-R8.

### Claim 5

A compound having the following structure:
and its tautomer
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
Q1 is —S—, —SO—, —SO2—, —CH2CH2—, —CH═CH—, —OCH2—, —SCH2—, —SOCH2—, or —SO2CH2;
V is O, S, NH, or NZ, or N-terminal linked amino acid, or halogen when R1 is absent;
R1 is absent, —H, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, —(CH2)nOZ, —C(O)Z, —C(O)OZ, —C(O)NHZ, —C(O)N(Z)2, —(CR1AR1B)r2OPO(OZ)2, —(CR2AR2B)r3PO(OZ)2, or C-terminal linked amino acid;
each Z is, independently, —H, —C1-C8 alkyl, —C4-C12 alkcycloalkyl, —C3-C9 alkheterocyclyl, wherein the heterocyclyl is 3 to 9 membered, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —C2-C8 alkenyl, or —C2-C8 alkynyl, or two Z, together with the atom(s) to which each is attached, join to form a 3- to 7-membered aromatic or non aromatic heterocycle;
each n is 1 or 2;
each r2 is an integer between 1-3;
each r3 is an integer between 0-2;
R2 is —H, -D, —OH, -halogen, —CN, —NO2, —SH, —CF3, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
R3 is —OH, -halogen, —CN, —NO2, —SH, —CF3, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
A1 and A2 are each, independently, —H, -D, -halogen, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, or —C7-C14 arylalkyl;
A3 is an aromatic heterocyclic ring selected from the group consisting of:
Q2, Q5, and Q6 are each, independently, N, N+—O−, or C;
Q3 and Q4 are each, independently, N, N+—O−, C, O, or S, wherein only one of Q3 and Q4 can be O or S;
wherein Q2, Q3, Q4, Q5, and Q6 simultaneously are C only if R4 and R5, R5 and R6, R6 and R7, or R7 and R8, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic heterocyclyl; and
R4, R5, R6, R7, and R8 are each, independently, absent, —H, -D, —OH, —O−, -halogen, —CN, —NO2, —SH, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, —PO(OZ)2, or R4 and R5, or R5 and R6, or R6 and R7, or R7 and R8, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle provided that the resulting ring system is not substituted benzimidazole, 5- or 6-chloro-imidazo[1,2-a]pyridine, 8-substituted quinoline, 2- or 4-chloro-quinoline, or 4-hydroxy-1,3-quinazoline;
wherein said compound comprises a carbocycle or heterocycle formed by combining R4 and R5, or R6 and R7, or R7 and R8 with the atoms to which each is attached; and
wherein the carbocycle or the heterocycle formed by R4 and R5, R5 and R6, R6 and R7, or R7 and R8, is substituted with 1, 2, 3, 4, 5, 6, or 7 substituents.

### Claim 6 (depends on 5)

The compound of claim 5, wherein the heterocycle formed by R4 and R5, R5 and R6, R6 and R7, or R7 and R8, is substituted with an amino group.

### Claim 7

A compound having the following structure:
and its tautomer
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
Q1 is —S—, —SO—, —SO2—, —CH2CH2—, —CH═CH—, —OCH2—, —SCH2—, —SOCH2—, or —SO2CH2—;
V is O, S, NH, or NZ, or N-terminal linked amino acid, or halogen when R1 is absent;
R1 is absent, —H, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, —(CH2)nOZ, —C(O)Z, —C(O)OZ, —C(O)NHZ, —C(O)N(Z)2, —(CR1AR1B)r2OPO(OZ)2, —(CR2AR2B)r3PO(OZ)2, or C-terminal linked amino acid;
each R1A, R1B, R2A, and R2B is, independently, H or C1-5 alkyl;
each Z is, independently, —H, —C1-3 alkyl, or two Z combine to form a 5-, 6-, or 7-membered ring
each n is 1 or 2;
each r2 is an integer between 1-3;
each r3 is an integer between 0-2;
R2 is —H, -D, —OH, -halogen, —CN, —NO2, —SH, —CF3, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
R3 is —OH, -halogen, —CN, —NO2, —SH, —CF3, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
A1 and A2 are each, independently, —H, -D, -halogen, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, or —C7-C14 arylalkyl;
A3 is an aromatic heterocyclic ring selected from the group consisting of:
Q2, Q5, and Q6 are each, independently, N, N+—O−, or C;
Q3 and Q4 are each, independently, N, N+—O−, C, O, or S, wherein only one of Q3 and Q4 can be O or S;
wherein Q2, Q3, Q4, Q5, and Q6 simultaneously are C only if R4 and R5, R5 and R6, R6 and R7, or R7 and R8, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic heterocyclyl; and
R4, R5, R6, R7, and R8 are each, independently, absent, —H, -D, —OH, —O−, -halogen, —CN, —NO2, —SH, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, —PO(OZ)2, or R4 and R5, or R5 and R6, or R6 and R7, or R7 and R8, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle provided that the resulting ring system is not substituted or unsubstituted benzimidazole, unsubstituted benzothiazole, unsubstituted imidazo[1,2-a]pyridine, 5- or 6-chloro-imidazo[1,2-a]pyridine, indole when R2 is C(O)OCH2CH3 unsubstituted quinoline, 8-substituted quinoline, unsubstituted quinoxaline, 2- or 4-chloro-quinoline, or 4-hydroxy-1,3-quinazoline,
wherein when A3 is unsubstituted pyridine-2-yl, and A1 and A2 are each —H, R3 is not —OH, —CF3, —C1-C3 alkyl, phenyl, difluorobenzyl, —NHC(O)CH3, or —NHC(O)CH2CH3;
wherein when A3 is unsubstituted pyridine-4-yl, and A1 and A2 are each —H, R3 is not —OH, —CH3, —CH2CH2CH3, or difluorobenzyl;
wherein when A3 is unsubstituted, 6-chloro, or 2,6-dichloro pyridine-3-yl, and A1 and A2 are each —H, R3 is not —OH, —CF3, —C1-C3 alkyl, phenyl, —C(O)OCH2CH3, or —NHC(O)CH3;
wherein when A3 is substituted or unsubstituted pyrazol-1-yl, R3 is not —OH;
wherein A3 is not 4-NO2-imidazol-2-yl; and
provided that
(a) R1 is —(CH2)nOZ, —C(O)Z, —C(O)OZ, —C(O)NHZ, —C(O)N(Z)2, —(CR1AR1B)r2OPO(OZ)2, or —(CR2AR2B)r3PO(OZ)2;
(b) R2 is —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
c) R3 is —OZ, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2; or
(d) at least one of R4, R5, R6, R7, and R8 is —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2.

### Claim 8 (depends on 7)

The compound of claim 7, wherein each Z is, independently, —H, —CH3, or —CH2CH3.

### Claim 9 (depends on 7)

The compound of claim 7, wherein both Z are either —H or —CH3.

### Claim 10 (depends on 7)

The compound of claim 7, wherein two Z, together with the atom to which each is attached, join to form a 5-, 6-, or 7-membered non aromatic heterocycle.

### Claim 11

A compound selected from the group consisting of:
or a stereoisomer, tautomer, prodrug, or pharmaceutically acceptable salt thereof.

### Claim 12

A compound selected from the group consisting of:
or a stereoisomer, tautomer, prodrug, or pharmaceutically acceptable salt thereof.

### Claim 13

A composition comprising a pharmaceutically acceptable carrier or vehicle and an effective amount of a compound having the following structure:
and its tautomer
including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein:
Q1 is —S—, —SO—, —SO2—, —CH2CH2—, —CH═CH—, —OCH2—, —SCH2—, —SOCH2—, or —SO2CH2—;
V is O, S, NH, or NZ, or N-terminal linked amino acid, or halogen when R1 is absent;
R1 is absent, —H, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, —(CH2)nOZ, —C(O)Z, —C(O)OZ, —C(O)NHZ, —C(O)N(Z)2, —(CR1AR1B)r2OPO(OZ)2, —(CR2AR2B)r3PO(OZ)2, or C-terminal linked amino acid;
each R1A, R1B, R2A, and R2B is, independently, H or C1-5 alkyl;
each Z is, independently, —H, —C1-C8 alkyl, —C4-C12 alkcycloalkyl, —C3-C9 alkheterocyclyl, wherein the heterocyclyl is 3 to 9 membered, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —C2-C8 alkenyl, or —C2-C8 alkynyl, or two Z, together with the atom(s) to which each is attached, loin to form a 3- to 7-membered aromatic or non aromatic heterocycle;
each n is 1 or 2;
each r2 is an integer between 1-3;
each r3 is an integer between 0-2;
R2 is —H, -D, —OH, -halogen, —CN, —NO2, —SH, —CF3, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
R3 is —OH, -halogen, —CN, —NO2, —SH, —CF3, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, or —PO(OZ)2;
A1 and A2 are each, independently, —H, -D, -halogen, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, or —C7-C14 arylalkyl;
A3 is an aromatic heterocyclic ring selected from the group consisting of:
Q2, Q5, and Q6 are each, independently, N, N+—O−, or C;
Q3 and Q4 are each, independently, N, N+—O−, C, O, or S, wherein only one of Q3 and Q4 can be O or S;
wherein Q2, Q3, Q4, Q5, and Q6 simultaneously are C only if R4 and R5, R5 and R6, R6 and R7, or R7 and R8, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic heterocyclyl; and
R4, R5, R6, R7, and R8 are each, independently, absent, —H, -D, —OH, —O−, -halogen, —CN, —NO2, —SH, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl, —C3-C12 cycloalkyl, —C6-C12 aryl, —C7-C14 arylalkyl, 3 to 9-membered aromatic or non aromatic heterocyclyl, —OZ, —N(Z)2, —C(NH)N(Z)2, —O(CH2)nOZ, —C(O)Z, —OC(O)Z, —OC(O)OZ, —OC(O)N(Z)2, —C(O)N(Z)2, —C(O)OZ, —SZ, —SOZ, —S(O)2Z, —NHC(O)Z, —NHS(O)2Z, —NHC(NH)N(Z)2, —NZC(NH)N(Z)2, —NHC(NCN)N(Z)2, —NZC(NCN)N(Z)2, —PO(OZ)2, or R4 and R5, or R5 and R6, or R6 and R7, or R7 and R8, together with the atoms to which each is attached, join to form a 5- to 6-membered aromatic or non aromatic carbocycle or heterocycle provided that the resulting ring system is not substituted or unsubstituted benzimidazole, unsubstituted benzothiazole, unsubstituted imidazo[1,2-a]pyridine, 5- or 6-chloro-imidazo[1,2-a]pyridine, indole when R2 is C(O)OCH2CH3 unsubstituted quinoline, 8-substituted quinoline, unsubstituted quinoxaline, 2- or 4-chloro-quinoline, or 4-hydroxy-1,3-quinazoline,
wherein when A3 is unsubstituted pyridine-2-yl, and A1 and A2 are each —H, R3 is not —OH, —CF3, —C1-C3 alkyl, phenyl, difluorobenzyl, —NHC(O)furan, —NHC(O)CH3, or —NHC(O)CH2CH3;
wherein when A3 is unsubstituted pyridine-4-yl, and A1 and A2 are each —H, R3 is not —OH, —CH3, —CH2CH2CH3, or difluorobenzyl;
wherein when A3 is unsubstituted, 6-chloro, or 2,6-dichloro pyridine-3-yl, and A1 and A2 are each —H, R3 is not —OH, —CF3, —C1-C3 alkyl, phenyl, —C(O)OCH2CH3, or —NHC(O)CH3;
wherein when A3 is substituted or unsubstituted pyrazol-1-yl, R3 is not —OH; and
wherein A3 is not 4-NO2-imidazol-2-yl.