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US 2022/0177452 A9Published application
2-Pyrimidone Analogs as Potent Antiviral Agents Against Alphaviruses
AssigneesSouthern Research Institute, Oregon Health & Science University
InventorsAshish Kumar Pathak, Corinne E. Augelli-Szafran, Atefeh Garzan, Daniel Steblow, Nicole Haese
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Abstract
The present disclosure is concerned with 2-pyrimidone compounds that are capable of inhibiting a viral infection and methods of treating alphavirus viral infections such as, for example, chikungunya, Eastern equine encephalitis (EEEV), Western equine encephalitis (WEEV), and Venezuelan equine encephalitis using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
Claims20
A compound having a structure represented by a formula:
- wherein n is 0, 1, or 2;
- wherein p is 0 or 1;
- wherein A is O, S, or NH;
- wherein R1 is selected from hydrogen and C1-C4 alkyl;
- wherein each of R2a and R2b is independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C4 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C1-C8 cyanoalkoxy, —OCy2, —OAr1, —O(C1-C4 alkyl)OR10, —O(C1-C4 alkyl)Ar1, —CO2R10, and Cy2;
- wherein each occurrence of R10, when present, is independently selected from hydrogen and C1-C4 alkyl;
- wherein each occurrence of Ar1, when present, is independently selected from C2-C5 heteroaryl and C6-C12 aryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
- wherein each occurrence of Cy2, when present, is independently selected from C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, and phenyl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
- or wherein R2a and R2b are covalently bonded and, together with the intermediate atoms, comprise a C5-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl or a C2-C5 heteroaryl, and are substituted with 0, 1, 2, or 3 groups independently selected from selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
- and
- wherein each of R3a and R3b, when present, is independently selected from hydrogen, halogen, C1-C4 alkyl, and C1-C4 haloalkyl;
- or wherein R3a and R3b, when present, are covalently bonded and, together with the intermediate atoms, comprise a C3-C4 cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
- wherein Cy1 is selected from C2-C9 heteroaryl, C6 aryl, and adamantyl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, and C3-C6 cycloalkyl;
- provided that when Cy1 is C2-C9 heteroaryl, then either (i) p is 1 and A is O or (ii) n is 1 or 2 and each of R3a and R3b are not hydrogen;
- provided that when Cy1 is C6 aryl, then p is 1 and either (i) A is O or (ii) each of R2a and R2b is hydrogen and at least one of R3a and R3b is not hydrogen;
- and
- provided that when Cy1 is
- and p is 0, then n is 0 or 2,
- or a pharmaceutically acceptable salt thereof.
16 more elements
A compound having a structure selected from:
- or a pharmaceutically acceptable salt thereof.
A method for treating a viral infection in a subject, the method comprising administering to the subject an effective amount of a compound having a structure represented by a formula:
- wherein n is 0, 1, or 2;
- wherein p is 0 or 1;
- wherein A is O, S, or NH;
- wherein R1 is selected from hydrogen and C1-C4 alkyl;
- wherein each of R2a and R2b is independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C4 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C1-C8 cyanoalkoxy, —OCy2, —OAr1, —O(C1-C4 alkyl)OR10, —O(C1-C4 alkyl)Ar1, —CO2R10, and Cy2;
- wherein each occurrence of R10, when present, is independently selected from hydrogen and C1-C4 alkyl;
- wherein each occurrence of Ar1, when present, is independently selected from C2-C5 heteroaryl and C6-C12 aryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
- wherein each occurrence of Cy2, when present, is independently selected from C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, and phenyl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
- or wherein R2a and R2b are covalently bonded and, together with the intermediate atoms, comprise a C5-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl or a C2-C5 heteroaryl, and are substituted with 0, 1, 2, or 3 groups independently selected from selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
- and
- wherein each of R3a and R3b, when present, is independently selected from hydrogen, halogen, C1-C4 alkyl, and C1-C4 haloalkyl;
- or wherein R3a and R3b, when present, are covalently bonded and, together with the intermediate atoms, comprise a C3-C4 cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
- wherein Cy1 is selected from C2-C9 heteroaryl, C6 aryl, and adamantyl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, and C3-C6 cycloalkyl;
- provided that when p is 1, A is S, and Cy1 is C6 aryl, then Cy1 is not substituted with a halogen group,
- or a pharmaceutically acceptable salt thereof, wherein the viral infection is due to an Alphavirus, thereby treating the viral infection.
12 more elements
Dependencies are inferred from the claim text.