# US 7,375,237 B2 · Pyrrolizine compounds useful as anti-inflammatory agents

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- Number: US 7,375,237 B2
- Document ID: US7375237B2
- Status: Granted
- Kind: B2
- Application number: 11/206,558
- Filed: 2005-08-18
- Published: 2006-03-09
- Granted: 2008-05-20
- Earliest claimed: 2004-08-18
- Assignees: Bristol-Myers Squibb Company; Cerep SA
- Inventors: T. G. Murali Dhar; Dharmpal S. Dodd; Dominique Potin; Michele Launay
- Web page: https://patentgrep.com/patent/US7375237B2

## CPC

- C07D 487/04: Ortho-condensed systems
- A61K 31/407: condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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)

## Abstract

Pyrrolizine compounds having the formula (I), or pharmaceutically-acceptable salts thereof, are effective in treating inflammatory or immune diseases, where A is a four- to seven-membered saturated ring, K is O or S, and R1, R2, R3 n, and M are defined in the specification.

## Claims

### Claim 1

A compound having the structure of formula (Ic):
or a pharmaceutically-acceptable salt, enantiomer, or diastereomer, thereof wherein:
M is methyl, ethyl, propyl, cyclopropyl, or CF3;
R3 is hydroxy or —OC(═O)phenyl;
R10 is chloro, fluoro, bromo, or cyano; and
R11 independently at each occurrence is chloro, fluoro, or bromo.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically-acceptable salt, enantiomer, or diastereomer thereof, in which each R11 is chloro.

### Claim 3

A compound selected from
(i)
7a-(4-Bromobenzyl)-2-(3,5-dichlorophenyl)-1-ethyl-5,6,7,7a-tetrahydro-3H-pyrrolizin-3-one;
7a-(4-Bromobenzyl)-1-cyclopropyl-2-(3,5-dichlorophenyl)-5,6,7,7a-tetrahydro-3H-pyrrolizin-3-one;
(6R)-7a-(4-Bromobenzyl)-2-(3,5-dichlorophenyl)-1-ethyl-6-hydroxy-5,6,7,7a-tetrahydro-3H-pyrrolizin-3-one;
(6R)-7a-(4-Bromobenzyl)-2-(3,5-dichlorophenyl)-1-ethyl-6-hydroxy-5,6,7,7a-tetrahydro-3H-pyrrolizin-3-one;
4-{[6-(3,5-Dichlorophenyl)-7-ethyl-5-oxo-2,3-dihydro-1H-pyrrolizin-7a(5H)-yl]methyl}benzonitrile;
4-{[(2R)-6-(3,5-Dichlorophenyl)-7-ethyl-2-hydroxy-5-oxo-2,3-dihydro-1H-pyrrolizin-7a(5H)-yl]methyl}benzonitrile;
(2S,7aR)-7a-(4-bromobenzyl)-6-(3,5-dichlorophenyl)-7-ethyl-5-oxo-2,3,5,7a-tetrahydro-1H-pyrrolizin-2-yl benzoate;
(2S,7aS)-7a-(4-Bromobenzyl)-6-(3,5-dichlorophenyl)-7-ethyl-5-oxo-2,3,5,7a-tetrahydro-1H-pyrrolizin-2-yl benzoate;
(6S, 7aS)-7a-(4-Bromobenzyl)-2-(3,5-dichlorophenyl)-1-ethyl-6-hydroxy-5,6,7,7a-tetrahydro-3H-pyrrolizin-3-one;
4-{[6-(3,5-Dichlorophenyl)-7-methyl-5-oxo-2,3-dihydro-1H-pyrrolizin-7a(5H)-yl]methyl}benzonitrile;
4-{[6-(3,5-Dichlorophenyl)-7-methyl-5-oxo-2,3-dihydro-1H-pyrrolizin-7a(5H)-yl]methyl}benzonitrile;
7a-(4-Cyanobenzyl)-6-(3,5-dichlorophenyl)-5-oxo-2,3,5,7a-tetrahydro-1H-pyrrolizine-7-carbonitrile;
7a-(4-Cyanobenzyl)-6-(3,5-dichlorophenyl)-5-oxo-2,3,5,7a-tetrahydro-1H-pyrrolizine-7-carbonitrile;
(2R)-7a-(4-cyanobenzyl)-6-(3,5-dichlorophenyl)-2-hydroxy-5-oxo-2,3,5,7a-tetrahydro-1H-pyrrolizine-7-carbonitrile; and
4-[6-(3,5-Dichloro-phenyl)-7-methoxy-5-oxo-2,3-dihydro-1H,5H-pyrrolizin-7a-ylmethyl]-benzonitrile; or
(ii) a pharmaceutically-acceptable salt, enantiomer, or diastereomer of (i), thereof.

### Claim 4 (depends on 1)

A pharmaceutical composition comprising (a) at least one compound according to claim 1, or a pharmaceutically acceptable salt thereof, and (b) a pharmaceutically acceptable carrier or diluent.

### Claim 5 (depends on 1)

A method of treating comprising: administering to the mammal in need of such treatment a therapeutically-effective amount of a compound according to claim 1.