Heterocycles as inhibitors of leucocyte adhesion and as VLA-4 an

Details Heterocycles as inhibitors of leucocyte adhesion and as VLA-4 an Heterocycles as inhibitors of leucocyte adhesion and as VLA-4 an

1997-11-17

1999-12-07

Richter, Johann

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

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

514398, 514 94, 514 89, 546 22, 5462744, 548112, 5483137, 5483147, 5483195, A01N 4340, A01N 5716, C07F 932, C07D23340

Patent

active

059984473

ABSTRACT:
Compounds of the formula I ##STR1## in which B, D, E, R, W, Y, Z, b, c, d, e, f, g and have the meanings indicated in the claims, are inhibitors of the adhesion and migration of leucocytes and/or antagonists of the adhesion receptor VLA-4 which belongs to the group of integrins. The invention relates to the use of compounds of the formula I, and of pharmaceutical preparations which contain such compounds, for the treatment and prophylaxis of diseases which are caused by an un desired extent of leucocyte adhesion and/or leucocyte migration or which are associated therewith or in which cell--cell or cell-matrix interactions play a part which are based on interactions of VLA-4 receptors with their ligands, for example of inflammatory processes, rheumatoid arthritis or allergic disorders, and it also relates to the use of compounds of the formula I for the production of pharmaceuticals for use in such diseases. It further relates to novel compounds of the formula I.

REFERENCES:
patent: 5424293 (1995-06-01), Zoller et al.
Mariano J. Elices, et al., "VCAM-1 on Activated Endothelium Interacts with the Leukocyte Integrin VLA-4 at a Site Distinct from the VLA-4/Fibronectin Binding Site", Cell, vol. 60, pp. 577-584, Feb. 1990.
G. Kilger, et al., "Molecular anaylsis of the physiological and pathophysiological role of .alpha..sub.4 -integrins", J. Mol. Med: Review, vol. 73, pp. 347-354, 1995.
Thomas B. Issekutz, et al., "Rat Blood Neutrophils Express Very Late Antigen 4 and it Mediates Migration to Arthritic Joint and Dermal Inflammation", J. Exp. Med., vol. 183, pp. 2175-2184, May 1996.
Bruce N. Cronstein, et al., "The Adhesion Molecules of Inflammation", Arthritis and Rheumatism, vol. 36, No. 2, pp. 147-157, Feb. 1993.

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