US 12,465,582 B2
(S)-2-amino-6-((3-aminopropyl)amino)hexanoic acid (APL) for use in the treatment of non-alcoholic steatohepatitis (NASH), liver inflammation, hepatocellular ballooning, liver fibrosis and steatosis
Salim Merali, Philadelphia, PA (US); Wayne E. Childers, Philadelphia, PA (US); Carlos Barrero, Philadelphia, PA (US); George C. Morton, Philadelphia, PA (US); and Mario Cesar Rico, Philadelphia, PA (US)
Assigned to Temple University—Of The Commonwealth System of Higher Education, Philadelphia, PA (US)
Appl. No. 17/996,830
Filed by Temple University—Of The Commonwealth System Of Higher Education, Philadelphia, PA (US)
PCT Filed Apr. 23, 2021, PCT No. PCT/US2021/028849
§ 371(c)(1), (2) Date Oct. 21, 2022,
PCT Pub. No. WO2021/217006, PCT Pub. Date Oct. 28, 2021.
Claims priority of provisional application 63/015,175, filed on Apr. 24, 2020.
Prior Publication US 2023/0172886 A1, Jun. 8, 2023
Int. Cl. A61K 31/198 (2006.01); A61K 9/00 (2006.01); A61P 1/16 (2006.01)
CPC A61K 31/198 (2013.01) [A61K 9/0056 (2013.01); A61P 1/16 (2018.01)] 37 Claims
 
1. A method for treating non-alcoholic steatohepatitis (NASH), said method comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to Formula I,

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of hydrogen, —(C1-C8)alkyl, —(C1-C8)alkenyl, —(C1-C8)alkynyl, unsubstituted or substituted -ara(C1-C6)alkyl, unsubstituted or substituted -heteroara(C1-C6)alkyl, where the substituents on said substituted ara(C1-C6)alkyl and substituted heteroara(C1-C6)alkyl are selected from the group consisting of halogen, —CN, —NO2, —NH2, —NH(C1-C6)alkyl, —N[(C1-C6)alkyl)]2, —OH, halo(C1-C6)alkyl, —(C1-C6)alkoxy, halo(C1-C6)alkoxy, —SH, thio(C1-C6)alkyl, —SONH2, —SO2NH2, —SO—(C1-C6)alkyl, —SO2—(C1-C6)alkyl, —NHSO2 (C1-C6)alkyl, and —NHSO2NH2;
R2 is selected from the group consisting of hydrogen, —(C1-C8)alkyl, —(C1-C8)alkenyl, —(C1-C8)alkynyl, unsubstituted or substituted -ara(C1-C6)alkyl, unsubstituted or substituted -heteroara(C1-C6)alkyl, where the substituents on said substituted ara(C1-C6)alkyl and substituted heteroara(C1-C6)alkyl are selected from the group consisting of halogen, —CN, —NO2, —NH2, —OH, halo(C1-C6)alkyl, —(C1-C6)alkoxy, halo(C1-C6)alkoxy, —SH, thio(C1-C6)alkyl, —SONH2, —SO2NH2, —SO—(C1-C6)alkyl, —SO2—(C1-C6)alkyl, —NHSO2 (C1-C6)alkyl, and —NHSO2NH2;
R3, R4, R7, R8, R9, R10, R13 and R14 are independently selected from the group consisting of hydrogen and —(C1-C6)alkyl;
R5 and R6 are independently selected from the group consisting of hydrogen, —(C1-C6)alkyl and —OH, provided that both R5 and R6 cannot be —OH;
R11 and R12 are independently selected from the group consisting of hydrogen, —(C1-C6)alkyl and —OH, provided that both R11 and R12 cannot be —OH;
m is 1, 2, 3 or 4;
n is 0, 1, 2, 3 or 4;
is 0, 1, 2, 3 or 4;
p is 1, 2, 3 or 4;
q is 0, 1, 2, 3 or 4; and
r is 0, 1, 2, 3 or 4.