US 12,215,108 B2
Development of potential antidotes for arsenicals
Mark J. Suto, Homewood, AL (US); Bini Mathew, Hoover, AL (US); Corinne E. Augelli-Szafran, Homewood, AL (US); Marina Fosso Yatchang, Chelsea, AL (US); Mohammad Athar, Hoover, AL (US); Anupam Agarwal, Mountain Brook, AL (US); Ritesh Kumar Srivastava, Vestavial Hills, AL (US); Suhail Muzaffar, Birmingham, AL (US); and Jasim Khan, Birmingham, AL (US)
Assigned to Southern Research Institute, Birmingham, AL (US); UAB Research Foundation, Birmingham, AL (US); and The United States Government as represented by the Department of Veterans Affairs, Washington, DC (US)
Filed by Southern Research Institute, Birmingham, AL (US); UAB Research Foundation, Birmingham, AL (US); and The United States Government as represented by the Department of Veterans Affairs, Washington, DC (US)
Filed on Jan. 10, 2023, as Appl. No. 18/095,429.
Claims priority of provisional application 63/298,162, filed on Jan. 10, 2022.
Prior Publication US 2023/0219958 A1, Jul. 13, 2023
Int. Cl. C07D 473/32 (2006.01); A61P 39/02 (2006.01)
CPC C07D 473/32 (2013.01) [A61P 39/02 (2018.01)] 15 Claims
 
1. A compound having a structure represented by a formula:

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wherein each of R1a, R1b, R1c, R1d, and R1e 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, and C1-C4 aminoalkyl;
wherein each of R2 and R3 is independently selected from hydrogen and C1-C4 alkyl;
wherein Cy1 is a structure having a formula selected from:

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wherein n, when present, is 0 or 1;
wherein Z, when present, is selected from —O—, —S—, and —NR20—;
wherein R20, when present, is selected from hydrogen and C1-C4 alkyl;
wherein each of R10a, R10b, R10c, R10d, R10e, and R10f, when present, 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, and C1-C4 aminoalkyl;
wherein each of R11a and R11b, when present, 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, and C1-C4 aminoalkyl;
wherein each of R12a, R12b, R12c, and R12d, when present, 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, and C1-C4 aminoalkyl; and
wherein R13, when present, is selected from —OH, —NH2, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; and
wherein Cy2 is a structure having a formula selected from:

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wherein m, when present, is 0 or 1;
wherein Q, when present, is selected from —O—, —S—, and —NR21—;
wherein R21, when present, is selected from hydrogen and C1-C4 alkyl;
wherein each of R14a, R14b, R14c, R14d, R14e, and R14f, when present, 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, and C1-C4 aminoalkyl;
wherein each of R15a and R15b, when present, 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, and C1-C4 aminoalkyl;
wherein each of R16a, R16b, R16c, and R16d, when present, 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, and C1-C4 aminoalkyl; and
wherein R17, when present, is 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, C1-C4 aminoalkyl, —CO2H, and —CO2 (C1-C4 alkyl),
provided that when Cy1 is

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 and at least seven of R10a, R10b, R10c, R10d, R10e, R10f, R11a, and R11b are hydrogen, then each of R1a, R1c, and R1e is halogen,
provided that when Cy1 is

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 then Cy2 is

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provided that when Cy1 is

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 and Cy2 is

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 then R17 is a non-hydrogen group, and
provided that when Cy1 is

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 Cy2 is

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 and at least seven of R14a, R14b, R14c, R14d, R14e, R14f, R15a, and R15b are hydrogen, then each of R12a, R12b, R12c, and R12d is hydrogen,
or a pharmaceutically acceptable salt thereof.