US 11,987,579 B2
Niclosamide analogues and therapeutic use thereof
Robert A. Mook, Chapel Hill, NC (US); Wei Chen, Chapel Hill, NC (US); Jiangbo Wang, Durham, NC (US); Xiu-Rong Ren, Durham, NC (US); and Herbert Kim Lyerly, Chapel Hill, NC (US)
Assigned to Duke University, Durham, NC (US)
Appl. No. 17/263,769
Filed by Duke University, Durham, NC (US)
PCT Filed Jul. 30, 2019, PCT No. PCT/US2019/044184
§ 371(c)(1), (2) Date Jan. 27, 2021,
PCT Pub. No. WO2020/028392, PCT Pub. Date Feb. 6, 2020.
Claims priority of provisional application 62/725,006, filed on Aug. 30, 2018.
Claims priority of provisional application 62/712,103, filed on Jul. 30, 2018.
Prior Publication US 2021/0179615 A1, Jun. 17, 2021
Int. Cl. C07D 471/04 (2006.01); A61K 45/06 (2006.01); A61P 35/04 (2006.01); C07D 235/10 (2006.01); C07D 249/18 (2006.01)
CPC C07D 471/04 (2013.01) [A61K 45/06 (2013.01); A61P 35/04 (2018.01); C07D 235/10 (2013.01); C07D 249/18 (2013.01)] 20 Claims
 
1. A compound of formula (I), or a pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
wherein,

OG Complex Work Unit Chemistry
is

OG Complex Work Unit Chemistry
X1 is N or CRx1;
X2 is N;
X3 is N or CRx3;
Z is aryl or heteroaryl, wherein the aryl and the heteroaryl are optionally substituted with 1, 2, 3, or 4RZ;
RA1 and RA2 are haloalkyl, halogen, oxo, cyano, nitro, —OH, alkoxy, or —C(O)alkyl;
Rx1 and Rx3 are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, cyano, haloalkyl, alkoxyalkyl, heteroalkyl, alkenyl, alkynyl, heterocycle, carboxyl, heterocyclealkyl, —OH, alkoxy, —OR4, —SR5, —NR6R7, and —NR8—SO2—R9;
Rz at each occurrence is independently selected from the group consisting of halogen, nitro, alkyl, cyano, haloalkyl, alkoxyalkyl, heteroalkyl, alkenyl, alkynyl, heterocycle, carboxyl, heterocyclealkyl, —OH, alkoxy, —OR4, —SR5, —NR6R7, —SO2—R9, and —NR8—SO2—R9;
R4 is selected from —C(O)-alkyl, —C(O)-alkenyl, —C(O)-heteroalkyl, —C(O)-heteroaryl, —C(O)-alkoxyalkyl, —C(O)—O-heteroalkyl, —C(O)—O-heteroaryl, —C(O)—O-alkyl, —C(O)—O-alkenyl, and —C(O)—O— alkoxyalkyl;
R5, R6 and R7 are each independently selected from hydrogen, alkyl, —C(O)-alkyl, —C(O)—O-alkyl, —C(O)—O-alkenyl, —C(O)-alkoxyalkyl, —C(O)—NH-alkyl, —C(O)-heterocycle, -alkenyl, alkynyl, and heteroalkyl;
R8 is selected from hydrogen and alkyl; and
R9 is selected from hydrogen, alkyl, aryl, heteroaryl, arylalkyl, heterocycle and heteroarylalkyl,
provided that Z is not benzo[d]thiazole or substituted benzo[d]thiazole.