# US 2014/0194485 A1 · Isotopologues of isoindole derivatives

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- Number: US 2014/0194485 A1
- Document ID: US20140194485A1
- Status: Published application
- Kind: A1
- Application number: 13/979,602
- Filed: 2012-01-12
- Published: 2014-07-10
- Earliest claimed: 2011-01-14
- Assignees: Celgene Corporation
- Inventors: Hon-Wah Man; Louise Michelle Cameron; Anthony Joseph Frank
- Web page: https://patentgrep.com/patent/US20140194485A1

## CPC

- A61K 31/4035: Isoindoles, e.g. phthalimide
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07D 209/46: with an oxygen atom in position 1
- C07D 209/48: with oxygen atoms in positions 1 and 3, e.g. phthalimide
- C07D 209/49: and having in the molecule an acyl radical containing a saturated three-membered ring, e.g. chrysanthemumic acid esters
- C07D 209/66: with oxygen atoms in positions 1 and 3
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Provided herein are isoindole derivatives, which is enriched with isotopes such as deuterium. Pharmaceutical compositions comprising the isotopes-enriched compounds, and methods of using such compounds are also provided.

## Claims

### Claim 1

A compound of formula:
or a stereoisomer thereof,
wherein at least one of R1 and R2 is hydrogen and the other is N(H)COR3, wherein R3 is C1-C3 alkyl or C1-C3 cycloalkyl; and
wherein one or more hydrogens are isotopically enriched with deuterium, and the remaining hydrogens are non-enriched hydrogen atoms.

### Claim 2 (depends on 1)

The compound of claim 1, which is:
or a pharmaceutically acceptable salt or solvate thereof, wherein:
at least one of Y1-Y23 is a hydrogen that is isotopically enriched with deuterium, and the others of Y1-Y23 are non-enriched hydrogen atoms.

### Claim 3 (depends on 2)

The compound of claim 2, wherein the compound is an (S)-isomer having a structure:

### Claim 4 (depends on 2)

The compound of claim 2, wherein one to five of Y1-Y23 is isotopically enriched with deuterium, and the others are non-enriched hydrogens.

### Claim 5 (depends on 2)

The compound of claim 2, wherein six to ten of Y1-Y23 are isotopically enriched with deuterium, and the others are non-enriched hydrogens.

### Claim 6 (depends on 2)

The compound of claim 2, wherein eleven to fifteen of Y1-Y23 are isotopically enriched with deuterium, and the others are non-enriched hydrogens.

### Claim 7 (depends on 2)

The compound of claim 2, wherein sixteen to twenty of Y1-Y23 are isotopically enriched with deuterium, and the others are non-enriched hydrogens.

### Claim 8 (depends on 2)

The compound of claim 2, wherein twenty one to twenty three of Y1-Y23 are isotopically enriched with deuterium, and the others are non-enriched hydrogens.

### Claim 9 (depends on 1)

The compound of claim 1, which is:
or a pharmaceutically acceptable salt or solvate thereof, wherein:
at least one of Y1-Y25 is a hydrogen that is isotopically enriched with deuterium, and the others of Y1-Y25 are non-enriched hydrogen atoms.

### Claim 10 (depends on 9)

The compound of claim 9, wherein the compound is an (S)-isomer having a structure:

### Claim 11 (depends on 9)

The compound of claim 9, wherein one to five of Y1-Y25 is isotopically enriched with deuterium, and the others are non-enriched hydrogens.

### Claim 12 (depends on 9)

The compound of claim 9, wherein six to ten of Y1-Y25 are isotopically enriched with deuterium, and the others are non-enriched hydrogens.

### Claim 13 (depends on 9)

The compound of claim 9, wherein eleven to fifteen of Y1-Y25 are isotopically enriched with deuterium, and the others are non-enriched hydrogens.

### Claim 14 (depends on 9)

The compound of claim 9, wherein sixteen to twenty of Y1-Y25 are isotopically enriched with deuterium, and the others are non-enriched hydrogens.

### Claim 15 (depends on 9)

The compound of claim 9, wherein twenty one to twenty five of Y1-Y25 are isotopically enriched with deuterium, and the others are non-enriched hydrogens.

### Claim 16 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof.

### Claim 17 (depends on 1)

A method of treating, managing or preventing a disease or disorder comprising administering to a patient a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein the disease or disorder is a TNFα or PDE4 mediated disorder.

### Claim 18 (depends on 17)

The method of claim 17, further comprising administering a second active agent.