US 12,121,500 B2
Inhibitors of Bunyaviridae and uses thereof
John Edwin Tavis, Kirkwood, MO (US); Amelia Pinto, St. Louis, MO (US); James Brien, St. Louis, MO (US); and Ryan Murelli, Belleville, NJ (US)
Assigned to Saint Louis University, St. Louis, MO (US); and Research Foundation of the City University of New York, New York, NY (US)
Filed by Saint Louis University, St. Louis, MO (US); and Research Foundation of The City University of New York, New York, NY (US)
Filed on May 12, 2021, as Appl. No. 17/318,329.
Claims priority of provisional application 63/023,576, filed on May 12, 2020.
Prior Publication US 2021/0393548 A1, Dec. 23, 2021
Int. Cl. A61K 31/122 (2006.01); A61K 31/165 (2006.01); A61K 31/215 (2006.01); A61K 31/341 (2006.01); A61K 31/381 (2006.01); A61K 31/4412 (2006.01); A61K 31/454 (2006.01); A61P 31/14 (2006.01)
CPC A61K 31/122 (2013.01) [A61K 31/165 (2013.01); A61K 31/215 (2013.01); A61K 31/341 (2013.01); A61K 31/381 (2013.01); A61K 31/4412 (2013.01); A61K 31/454 (2013.01); A61P 31/14 (2018.01)] 17 Claims
 
1. A method of treating Rift Valley fever in a patient comprising administering to the patient a therapeutically effective amount of a compound according to the formula:

OG Complex Work Unit Chemistry
wherein:
R1 is hydroxy or a group of the formula: SC(O)R1′, wherein:
R1′ is an amino acid residue, a protected amino acid residue, aryl(C≤12), heteroaryl(C≤12), aralkyl(C≤12), or a substituted version of these three groups
R2 and R5 are each independently selected from hydrogen, halo, hydroxy, aryl(C≤12), substituted aryl(C≤12), acyl(C≤12), substituted acyl(C≤12), —C(O)R′, or —S(O)xR″, wherein:
R′ is —X1—Y1, wherein:
X1 is alkanediyl(C≤8), alkenediyl(C≤8), or a substituted version thereof; and
Y1 is aryl(C≤12), heteroaryl(C≤12), or a substituted version thereof;
x is 0, 1, or 2;
R″ is alkyl(C≤12), aryl(C≤12), aralkyl(C≤12), or a substituted version thereof;
R3 is hydrogen, alkyl(C≤12), or substituted alkyl(C≤12);
R4 is hydrogen or alkyl(C≤12), cycloalkyl(C≤12), aryl(C≤18), heteroaryl(C≤18), or a substituted version of these four groups; —C(O)Ra, —S(O)yRb, —C(O)N(Rc)Rd, or

OG Complex Work Unit Chemistry
wherein:
Ra is alkyl(C≤12), cycloalkyl(C≤12), aryl(C≤12), heteroaryl(C≤12), heterocycloalkyl(C≤12), alkoxy(C≤12), or —X2—Y2, wherein:
X2 is arenediyl(C≤12) or substituted arenediyl(C≤12); and
Y2 is aryl(C≤12), heteroaryl(C≤12), or a substituted version thereof;
Rb is aryl(C≤12), heteroaryl(C≤12), or a substituted version thereof;
Rc is hydrogen, alkyl(C≤6), or substituted alkyl(C≤6);
Rd is alkyl(C≤12), cycloalkyl(C≤12), aryl(C≤12), heteroaryl(C≤12), aralkyl(C≤12), heterocycloalkyl(C≤12), or a substituted version thereof, or —X3—Y3;
wherein:
X3 is arenediyl(C≤12), -alkanediyl(C≤8)-arenediyl(C≤12), or a substituted version thereof; and
Y3 is aryl(C≤12), heteroaryl(C≤12), aralkyl(C≤12), heterocycloalkyl(C≤12), aralkoxy(C≤12), or a substituted version thereof;
Re is aryl(C≤12), heteroaryl(C≤12), aralkyl(C≤18), or a substituted version thereof, or a group of the formula:

OG Complex Work Unit Chemistry
R6 is hydroxy;
or a pharmaceutically acceptable salt of either of these formulae.