Substituted derivatives of isoindoles

Patent metadata

Field	Value
Publication number	US-12454535-B2
Application number	US-202519034407-A
Country	US
Kind code	B2
Filing date	Jan 22, 2025
Priority date	Jul 26, 2023
Publication date	Oct 28, 2025
Grant date	Oct 28, 2025

Abstract

Provided are substituted derivatives of 5-(4-chlorophenyl)-2,3-dihydroimidazo[1,2-b]isoindol-5-ol having Formula (I):

as well as their stereoisomers and their pharmaceutically acceptable salts. Such substituted derivatives may be used, for example, in pharmaceutical compositions for the treatment of central nervous system diseases or disorders. In addition, methods of making such substituted derivatives are also provided.

First claim

What is claimed is:

1 . An isoindoline derivative of Formula I, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:
R 1 comprises a dioxolanylmethyl group;
and
R 2 -R 5 are each independently H or alkyl;
R 6 -R 11 , R 13 and R 14 are each independently H, alkyl, alkoxy, F, Cl, Br, CF 3 or I, and
R 12 is alkyl, alkoxy, F, Cl, Br, CF 3 or I.

2 . An isoindoline derivative, wherein the isoindoline derivative is:

or a stereoisomer or a pharmaceutically acceptable salt thereof.

3 . An isoindoline derivative, wherein the isoindoline derivative is selected from the group consisting of:
5-(benzyloxy)-5-(4-chlorophenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-1), 5-(4-chlorophenyl)-5-((4-methoxybenzyl)oxy)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-2), 5-(allyloxy)-5-(4-chlorophenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-3), 5-(4-chlorophenyl)-5-(2-methoxyethoxy)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-4), methyl 2-((5-(4-chlorophenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindol-5-yl)oxy)acetate (I-5), 5-(benzo[d][1,3]dioxol-5-ylmethoxy)-5-(4-chlorophenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-7), 5-(4-chlorophenyl)-5-((3-methylbut-2-en-1-yl)oxy)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-9), (E)-5-(4-chlorophenyl)-5-((3,7-dimethylocta-2,6-dien-1-yl)oxy)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-11), 5-(4-chlorophenyl)-5-(2-(2-(2-methoxyethoxy) ethoxy) ethoxy)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-12), 5-(4-chlorophenyl)-5-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)oxy)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-13), 5-(4-chlorophenyl)-5-((4-(trifluoromethyl)benzyl)oxy)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-14), 5-(4-chlorophenyl)-5-((3,4-dimethoxybenzyl)oxy)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-15), 5-((4-chlorobenzyl)oxy)-5-(4-chlorophenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-16), (E)-5-(4-chlorophenyl)-5-((4-methylpent-2-en-1-yl)oxy)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-17), (E)-5-(4-chlorophenyl)-5-((3-(4-(trifluoromethyl)phenyl) allyl)oxy)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-18), 5-((1,3-dioxolan-2-yl) methoxy)-5-(4-chlorophenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-19), (E)-5-((3-(benzo[d][1,3]dioxol-5-yl) allyl)oxy)-5-(4-chlorophenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-20), 5-(4-chlorophenyl)-5-(cinnamyloxy)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-21), (E)-5-(4-chlorophenyl)-5-((3-(4-fluorophenyl) allyl)oxy)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-22), and (E)-5-(4-chlorophenyl)-5-((3-(4-chlorophenyl) allyl)oxy)-2,5-dihydro-3H-imidazo[2,1-a]isoindole (I-23); or a stereoisomer or a pharmaceutically acceptable salt thereof.

4 . A composition comprising the isoindoline derivative of claim 1 , and a pharmaceutically acceptable excipient.

5 . The isoindoline derivative of claim 1 , wherein R 12 is Cl.

Assignees

• Supernus Pharmaceuticals Inc

Inventors

• Olson Gary L
• Nallaganchu Bhaskara Rao
• Sun Yanjun

Classifications

• C07D405/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D403/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D233/14

  Radicals substituted by oxygen atoms · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K31/4188

  condensed with other heterocyclic ring systems, e.g. biotin, sorbinil · CPC title