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US 2020/0399271 A1Published application
Xanthine analogs as potent anti-west nile viral agents
AssigneesSouthern Research Institute, Oregon Health & Science University
InventorsAshish Kumar Pathak, Theresa Ha Nguyen, Corinne E. Augelli-Szafran, Alec Jay Hirsch, Jessica Lee Smith
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Abstract
The present disclosure is concerned with xanthine analogs, methods of making xanthine analogs, and methods of treating West Nile virus using these analogs. 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 selected from 0, 1, and 2;
- wherein each occurrence of A, when present, is individually selected from —C(O)— and —CH2—, provided that no more than one occurrence of A, when present, is —C(O)—;
- wherein Z is selected from N and CR10;
- wherein R10, when present, is selected from hydrogen and C1-C4 alkyl;
- wherein R1 is selected from hydrogen, C1-C4 alkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, —CH2(C3-C6 cycloalkyl), —(C1-C4 alkyl)-CO2H, and —(C1-C4 alkyl)-O—(C1-C4 alkyl)-OH;
- wherein R2 is selected from —OH, C1-C4 alkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, —CH2(C3-C6 cycloalkyl), —(C1-C4 alkyl)-CO2H, and —(C1-C4 alkyl)-O—(C1-C4 alkyl)-OH;
- wherein R3 is selected from C1-C4 alkyl and Ar1, provided that when R3 is methyl then R10 is not hydrogen and provided that when Z is N then R3 is Cy2;
- wherein Ar1, when present, is selected from 6-membered aryl and 6-membered heteroaryl, 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 —CO2(C1-C4 alkyl);
- and
- wherein each of R4a, R4b, R4c, and R4d is independently selected from hydrogen, 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, —CO2H, and —CO2(C1-C4 alkyl);
- wherein Cy1 is selected from cyclohexyl, 6-membered aryl, and 6-membered heteroaryl, 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 —CO2(C1-C4 alkyl),
- provided that when n is 1, A is CH2, R1 is hydrogen or methyl, R2 is methyl, R3 is 6-membered aryl, and Cy1 is 6-membered aryl, then R10, when present, is C1-C4 alkyl, and
- provided that when each occurrence of A, when present, is CH2, R1 is hydrogen, R2 is methyl, R3 is 6-membered aryl, and Cy1 is 6-membered aryl, then Z is CR10,
- or a pharmaceutically acceptable salt thereof.
11 more elements
A compound selected from:
- or a pharmaceutically acceptable salt thereof.
A method for treating West Nile virus (WNV) in a subject, the method comprising administering to the subject an effective amount of at least one compound having a structure represented by a formula:
- wherein n is selected from 0, 1, and 2;
- wherein each occurrence of A, when present, is individually selected from —C(O)— and —CH2—, provided that no more than one occurrence of A, when present, is —C(O)—;
- wherein Z is selected from N and CR10;
- wherein R10, when present, is selected from hydrogen and C1-C4 alkyl;
- wherein R1 is selected from hydrogen, C1-C4 alkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, —CH2(C3-C6 cycloalkyl), —(C1-C4 alkyl)-CO2H, and —(C1-C4 alkyl)-O—(C1-C4 alkyl)-OH;
- wherein R2 is selected from —OH, C1-C4 alkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, —CH2(C3-C6 cycloalkyl), —(C1-C4 alkyl)-CO2H, and —(C1-C4 alkyl)-O—(C1-C4 alkyl)-OH;
- wherein R3 is selected from C1-C4 alkyl and Ar1;
- wherein Ar1, when present, is selected from 6-membered aryl and 6-membered heteroaryl, 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 —CO2(C1-C4 alkyl);
- and
- wherein each of R4a, R4b, R4c, and R4d is independently selected from hydrogen, 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, —CO2H, and —CO2(C1-C4 alkyl);
- wherein Cy1 is selected from cyclohexyl, 6-membered aryl, and 6-membered heteroaryl, 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 —CO2(C1-C4 alkyl),
- provided that when n is 1, A is CH2, R1 is hydrogen or methyl, R2 is methyl, R3 is 6-membered aryl, and Cy1 is 6-membered aryl, then R10, when present, is C1-C4 alkyl,
- or a pharmaceutically acceptable salt thereof, thereby treating West Nile virus.
10 more elements
Dependencies are inferred from the claim text.