Heterocyclic compounds and their therapeutic use

Details Heterocyclic compounds and their therapeutic use Heterocyclic compounds and their therapeutic use

2002-05-16

2003-11-04

Fay, Zohreh (Department: 1614)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C514S912000

Reexamination Certificate

active

06642254

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to novel heterocyclic compounds and to their formulation and use as pharmaceuticals.
BACKGROUND OF THE INVENTION
EP-A-0498722 describes quinoline derivatives as angiotensin A
2
and endothelin inhibitors.
The modes of action of phosphodiesterases and also tumour necrosis factors (TNF), and the therapeutic utilities of inhibitors thereof, are described in WO-A-9744036 and U.S. Pat. No. 5,804,588, the contents of which are incorporated herein by reference. These publications specifically disclose quinoline carboxamides having such inhibitory activity.
SUMMARY OF THE INVENTION
This invention provides novel compounds having therapeutic utility, in particular for the treatment of disease states associated with proteins which mediate cellular activity, for example by inhibiting TNF and/or PDE IV. According to the invention, the compounds are of formula (i):
wherein
R
1
is CH
3
, CH
2
F, CHF
2
or CF
3
;
R
2
is CH
3
or CF
3
,
R
3
is F, Cl, Br, CN or CH
3
, and
R
4
is H, F, Cl, Br, CN or CH
3
,
or a pharmaceutically-acceptable salt thereof.
In summary, the compounds of the invention are N-oxides of the corresponding free bases which are disclosed, some specifically, in WO-A-9744036. The novel compounds have superior solubility, improved metabolic stability, and an improved pharmacokinetic profile. The compound of Example 8 is particularly preferred.
This invention provides also a method for mediating or inhibiting the enzymatic activity or catalytic activity of PDE IV in a mammal in need thereof and for inhibiting the production of TNF in a mammal in need thereof which comprises administering to said mammal an effective amount of a compound of Formula (i) or a pharmaceutically-acceptable salt thereof.


REFERENCES:
patent: 5324839 (1994-06-01), Clemence et al.
patent: 5804588 (1998-09-01), Dyke et al.
patent: 2002/0068827 (2002-06-01), Giardina et al.
patent: WO 97/19926 (1997-06-01), None
patent: WO 97/44036 (1997-11-01), None
patent: WO 97/48697 (1997-12-01), None
Regan, J. et al. “2-substituted-4-methoxybenzimidazol-based PDE4 Inhibitors”Bioorganic&Medicinal Chemistry Letters, 1998, pp. 2737-2742, vol. 8, Issue 19.
Hulme, C. et al. “Orally Active Indole N-oxide PDE4 Inhibitors”Bioorganic&Medicinal Chemistry Letters, 1998, pp. 3053-3058, vol. 8, Issue 21.

Affiliated with

Also associated with

Rating

Heterocyclic compounds and their therapeutic use does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Heterocyclic compounds and their therapeutic use, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Heterocyclic compounds and their therapeutic use will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3148440