Phenyl-keto-imidazolidine thioamide derivatives

Details Phenyl-keto-imidazolidine thioamide derivatives Phenyl-keto-imidazolidine thioamide derivatives

2001-05-23

2002-11-12

Rotman, Alan L. (Department: 1625)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C548S311100, C548S314700, C546S272700, C544S171000, C544S263000

Reexamination Certificate

active

06479666

ABSTRACT:

BACKGROUND OF THE INVENTION
Vascular cell adhesion molecule-1 (VCAM-1), a member of the immunoglobulin (Ig) supergene family, is expressed on activated, but not resting, endothelium. The integrin VLA-4 (a
4
b
1
), which is expressed on many cell types including circulating lymphocytes, eosinophils, basophils, and monocytes, but not neutrophils, is the principal receptor for VCAM-1. Antibodies to VCAM-1 or VLA-4 can block the adhesion of these mononuclear leukocytes, as well as melanoma cells, to activated endothelium in vitro. Antibodies to either protein have been effective at inhibiting leukocyte infiltration and preventing tissue damage in several animal models of inflammation. Anti-VLA-4 monoclonal antibodies have been shown to block T-cell emigration in adjuvant-induced arthritis, prevent eosinophil accumulation and bronchoconstriction in models of asthma, and reduce paralysis and inhibit monocyte and lymphocyte infiltration in experimental autoimmune encephalitis (EAE). Anti-VCAM-1 monoclonal antibodies have been shown to prolong the survival time of cardiac allografts. Recent studies have demonstrated that anti-VLA-4 mAbs can prevent insulitis and diabetes in non-obese diabetic mice, and significantly attenuate inflammation in the cotton-top tamarin model of colitis.
Thus, compounds which inhibit the interaction between &agr;
4
-containing integrins and VCAM-1 will be useful as therapeutic agents for the treatment of inflammation resulting from chronic inflammatory diseases such as rheumatoid arthritis, multiple sclerosis (MS), asthma, and inflammatory bowel disease (IBD).
CROSS REFERENCE TO RELATED APPLICATIONS
This application is related to:
Chen, et al. U.S. Ser. No. 09/138,353 filed Aug. 21, 1998, Title: N-ALKANOYLPHENYLALANINE DERIVATIVES; and
Chen, et al. U.S. Ser. No. 09/137,798 filed Aug. 21, 1998,
Title: N-AROYLPHENYLALANINE DERIVATIVES.
SUMMARY OF THE INVENTION
It has been discovered that compounds of the formula:
and the pharmaceutically acceptable salts and esters thereof wherein X and Y are as defined below, inhibit the binding of VCAM-1 to VLA-4 and are useful in treating inflammation associated with chronicinflammatory diseases such as rheumatoid arthritis (RA), multiple sclerosis, (MS), asthma, and inflammatory bowel disease (I BD).


REFERENCES:
patent: 6229011 (2001-05-01), Chen et al.

Affiliated with

Also associated with

Rating

Phenyl-keto-imidazolidine thioamide derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Phenyl-keto-imidazolidine thioamide derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Phenyl-keto-imidazolidine thioamide derivatives will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2924825