US 2026/0263485 A1 · AMINOSTEROL COMPOUNDS, AMINOSTEROL-CYCLODEXTRIN FORMULATIONS, AND METHODS OF USING THE SAME

Abstract

Described are novel aminosterol compounds and additionally aminosterol-cyclodextrin formulations suitable for injectable administration, and methods of using the same.

Claims32

Dependent claims

An aminosterol compound, or a pharmaceutically acceptable salt, solvate, prodrug, enantiomer, or derivative thereof, having a structure selected from the group consisting of:

An aminosterol compound of Formula (I):

wherein:
R1 is an optionally substituted C1-C8 alkyl, optionally substituted 2 to 8-membered heteroalkyl, optionally substituted heterocyclyl, or optionally substituted C3-C8 cycloalkyl;
R2 is H or —C(O)R5, wherein R5 is an optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C1-C6 alkyl, optionally substituted heterocyclyl, or optionally substituted C3-C8 cycloalkyl;
and
R3 and R4 are each independently H or an optionally substituted 2 to 14-membered heteroalkyl;
or a pharmaceutically acceptable salt, solvate, prodrug, or derivative thereof;
wherein the compound is not:
(24R)-3β-({3-[(3-Aminopropyl)amino]propyl}amino)-7α-hydroxycholestan-24-yl hydrogen sulfate (squalamine);
(3R,6R)-6-((3S,5R,7R,8R,9S,10S,13R,14S,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptan-3-yl hydrogen sulfate (aminosterol 1436);
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic acid (ENT-03);
(2R,6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic acid (C25 (R) ENT-03);
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic-2,3,3-d3 acid (ENT-03 d3);
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-(benzoyloxy)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic acid;
(6R)-6-((3R,5S,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic acid;
(6R)-6-((3R,5S,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic acid;
(6R)-6-((3R,5S,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic acid;
(6R)-6-((3R,5S,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic-2-d acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic-2-d acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic-2-d acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic-2-d acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-(methyl-d3)heptanoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-(methyl-d3)heptanoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-(methyl-d3)heptanoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-(methyl-d3)heptanoic acid;
(6R,E)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylhept-2-enoic acid;
(6R,E)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylhept-2-enoic acid;
(6R,E)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylhept-2-enoic acid;
(6R,E)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylhept-2-enoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-3-hydroxy-2-methylheptanoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-3-hydroxy-2-methylheptanoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-3-hydroxy-2-methylheptanoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-3-hydroxy-2-methylheptanoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)heptan-3-one;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)heptan-3-one;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)heptan-3-one;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)heptan-3-one;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methyl-3-oxoheptanoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methyl-3-oxoheptanoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methyl-3-oxoheptanoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methyl-3-oxoheptanoic acid;
methyl(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methyl-3-oxoheptanoate;
methyl(6R)-6-((3 S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methyl-3-oxoheptanoate;
methyl(6R)-6-((3 S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methyl-3-oxoheptanoate;
methyl(6R)-6-((3 S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methyl-3-oxoheptanoate;
isopropyl(6R)-6-((3 S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methyl-3-oxoheptanoate;
isopropyl(6R)-6-((3 S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methyl-3-oxoheptanoate;
isopropyl(6R)-6-((3 S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methyl-3-oxoheptanoate;
isopropyl(6R)-6-((3 S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methyl-3-oxoheptanoate;
(6R)-6-((3 S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2,3-dihydroxy-2-methylheptanoic acid;
(6R)-6-((3 S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2,3-dihydroxy-2-methylheptanoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2,3-dihydroxy-2-methylheptanoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2,3-dihydroxy-2-methylheptanoic acid;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptane-2,3-diol;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptane-2,3-diol;
(3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-17-((2R)-5,6-dihydroxy-6-methylheptan-2-yl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-7,12-diol;
(3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-17-((2R)-5, 6-dihydroxy-6-methylheptan-2-yl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-7,12-diol;
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-ammoniobutyl)ammonio)propyl)ammonio)-7,12-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoate (ENT-05);
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-ammoniobutyl)ammonio)propyl)ammonio)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoate (ENT-06);
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-ammoniopropyl)ammonio)butyl)ammonio)propyl)ammonio)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-3-hydroxy-2-methylheptanoate-2,3-d2;
(2S,6R)-6-((3 S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic acid (C25 (S) ENT-03);
(2R,6R)-6-((3R,5S,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic acid;
(2S,6R)-6-((3R,5S,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic acid;
(2R,6R)-6-((3 S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic acid (C25 (R) ENT-06);
(2S,6R)-6-((3 S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptanoic acid (C25 (S) ENT-06);
(6R)-6-((3 S,5R,7R,10S,13R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-(methyl-d3)heptan-3-yl-1,1,1,2-d4 hydrogen sulfate (D7-squalamine);
(3R,6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-aminobutyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylheptan-3-yl-3-d hydrogen sulfate (24-D1-squalamine);
or
(6R)-6-((3S,5R,7R,10S,13R,17R)-3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-(methyl-d3)heptan-3-yl-1,1,1,2-d4 hydrogen sulfate (D7-1436).

66 more elements

Dependencies are inferred from the claim text.

Facts

Application

18/877,724Filed 27 Jun 2023

Priority

29 Jun 2022

Published

10 Sep 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification19 codes

A61K 31/58
Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids: containing heterocyclic rings, e.g. danazol,…
A61K 47/59
The modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule: obtained otherwise than by…
A61K 9/0019
Galenical forms characterised by the site of application: injectable compositions; Intramuscular, intravenous, arterial, subcutaneous…
A61K 9/08
Medicinal preparations characterised by special physical form: solutions

Family

Application63/356,910Us provisional application · filed 29 Jun 2022

Application63/459,107Us provisional application · filed 13 Apr 2023

Application63/461,875Us provisional application · filed 25 Apr 2023

US 2026/0263485 A1This patent

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Abstract

Described are novel aminosterol compounds and additionally aminosterol-cyclodextrin formulations suitable for injectable administration, and methods of using the same.

Aminosterol compounds, aminosterol-cyclodextrin formulations, and methods of using the same

Life of this patent

Abstract

Claims32

Aminosterol compounds, aminosterol-cyclodextrin formulations, and methods of using the same

Life of this patent

Abstract

Claims32