Cyclic peptides that inhibit the interaction of vascular cell adhesion molecule 1 (VCAM-1) and fibronectin with integrin very late antigen 4 (VLA-4)

摘要

Cyclic peptides of herein described formula wherein: AA1 is an L or D amino acid selected form Ile, Leu, Pro, Tic, Val, tert-Leu, tert-butyl-Ala, Phe, Nle, Met and Ala; AA2 is an L amino acid selected from Leu, Ile, Phe, Val, tert-Leu, Nle, Cha and tert-butyl-Ala; AA3 is an L amino acid selected from Asp or Glu; AA4 is an L amino acid selected from Val Leu, Ile, Phe, Cha, Nle, Nva; and each amino acid is optionally independently alkylated with C1-4 alkyl group; LINKER represents a linking moiety for linking N terminus of AA1 to C terminus of AA4 to form a cyclic peptide containing a heterocyclic ring having 17 to 30 members. The cyclic peptides inhibit the interaction of vascular cell adhesion molecule-1 and fibronectin with integrin very late antigen (VLA) 4 and have therapeutic applications such as in rheumatoid arthritis or multiple sclerosis.