US 11,925,611 B2
Use of ZT-1A and analogs thereof to prevent and/or treat neurodegenerative and neurocognitive disorders
Dandan Sun, Pittsburgh, PA (US); and Mohammad Iqbal Hossain Bhuiyan, Pittsburgh, PA (US)
Assigned to United States Government as represented by the Department of Veterans Affairs, Washington, DC (US); and University of Pittsburgh - of the Commonwealth of Higher Education, Pittsburgh, PA (US)
Filed by United States Government as Represented by the Department of Veterans Affairs, Washington, DC (US); and University of Pittsburgh—of the Commonwealth of Higher Education, Pittsburgh, PA (US)
Filed on Mar. 25, 2022, as Appl. No. 17/704,789.
Claims priority of provisional application 63/166,847, filed on Mar. 26, 2021.
Prior Publication US 2022/0313632 A1, Oct. 6, 2022
Int. Cl. A61K 31/167 (2006.01); A61P 25/28 (2006.01)
CPC A61K 31/167 (2013.01) [A61P 25/28 (2018.01)] 18 Claims
 
1. A method for treating and/or preventing a neurodegenerative disease or a neurocognitive disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound having a structure represented by a formula:

OG Complex Work Unit Chemistry
wherein each of X1 and X2 is independently halogen;
wherein R1 is selected from —OH, —SR10, and —NR11aR11b;
wherein each of R10, R11a,and R11b, when present, is independently selected from hydrogen and C1-C4 alkyl;
wherein each of R2a, R2b, R2c, and R2d is independently selected from hydrogen, halogen, —NO2, —CN, —OH, —SH, —NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino;
wherein each of R3a, R3b, R3c, and R3d is independently selected from hydrogen, halogen, —NO2, —CN, —OH, —SH, —NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino;
wherein R4 is selected from hydrogen and C1-C4 alkyl; and
wherein R5 is C1-C4 alkyl, provided that the compound is not:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein the subject has not been diagnosed as having had an ischemic stroke prior to the administering step, and
wherein the neurodegenerative disease is selected from Alzheimer's disease, cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy (CADASIL), Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS/Lou Gehrig's disease), Multiple Sclerosis, spinal muscular atrophy, spinal and bulbar muscular atrophy, familial spastic paraparesis, Machado Joseph disease, Friedreich's ataxia, and Lewy body disease.