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Cyclic peptides that are cell adhesion inhibiting compounds that inhibit the interaction of vascular cell adhesion molecule-1 and fibronectin with integrin very late antigen and mucosal addressin cell adhesion molecule-1
Cyclic peptides that are cell adhesion inhibiting compounds that inhibit the interaction of vascular cell adhesion molecule-1 and fibronectin with integrin very late antigen and mucosal addressin cell adhesion molecule-1
Cyclic peptide of formula (I) where Xaa1 is selected from L-amino acids selected from Phe, Lys and Arg; D-amino acids selected from Phe and Met, the L- and D-amino acid optionally substituted on its 'alpha'-carbon or its 'alpha'-amino group with a C1-4alkyl group; and MeIle; Xaa2, Xaa3 and Xaa4 are respectively Leu, Asp and Val, optionally substituted on their 'alpha'-carbon or 'alpha'-amino group with a C1-4alkyl group; X1 is selected from D-amino acids selected from Ala, Phe, Arg, Lys, Trp, hArg(Et)2, Orn(CHMe2), Orn(Me2), Lys(CHMe2) and Arg(Pmc), optionally substituted on their 'alpha'-carbon or 'alpha'-amino group with a C1-4alkyl group; Formula (II); NH(CH2)5CO; and NH(CH2)2S(CH2)yCO, where y is 1 or 2; X2 is selected from D-amino acids selected from Ala, Arg, Lys, His, hArg(Et)2, Orn(CHMe2), and Orn(Me2), optionally substituted on their 'alpha'-carbon or 'alpha'-amino group with a C1-4alkyl group; NH(CH2)2SCH2CO; and NH(CH2)xCO, where x is 2 or 3; Xaa5 and Xaa6 are each independently a D-amino acid selected from Ala and Arg, optionally substituted on its 'alpha'-carbon or 'alpha'-amino group with a C1-4alkyl group; p is 0 or 1; and q is 0 or when p is 1, q is 0 or 1; or a salt thereof. The cyclic peptides inhibit the interaction of vascular cell adhesion molecule-1 and fibronectin with integrin very late antigen 4 [VLA-4] (a4b1) and of mucosal addressin cell adhesion molecule -1 (MAdCAM-1) with integrin a4b7. They have therapeutic applications such as in rheumatoid arthritis, multiple sclerosis, asthma, psoriasis, inflammatory bowel disease and insulin-dependent diabetes.
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