N-aryl-prolyl-dipeptides as potent antagonists of VLA-4.

The design, synthesis, and biological evaluation of N-arylprolyl-dipeptide derivatives as small molecule VLA-4 antagonists is described. Potency against VLA-4 and alpha(4)beta(7) and rat pharmacokinetic evaluation revealed some advantages over the related N-(arylsulfonyl)-prolyl-dipeptide analogues.

[1]  S. Adams,et al.  Small-Molecule VLA-4 Antagonists , 2001 .

[2]  F. Albericio,et al.  EFFICIENCY IN PEPTIDE COUPLING : 1-HYDROXY-7-AZABENZOTRIAZOLE VS 3,4-DIHYDRO-3-HYDROXY-4-OXO-1,2,3-BENZOTRIAZINE , 1995 .

[3]  A. El‐Faham,et al.  Peptide Coupling in the Presence of Highly Hindered Tertiary Amines , 1996 .

[4]  D. Ma,et al.  Synthesis of chiral N-aryl-α-amino acids by PdCu catalyzed couplings of chiral α-amino acids with aryl halides , 1996 .

[5]  N. Fotouhi,et al.  Cyclic thioether peptide mimetics as VCAM-VLA-4 antagonists. , 2000, Bioorganic & medicinal chemistry letters.

[6]  M. Maccoss,et al.  The discovery of sulfonylated dipeptides as potent VLA-4 antagonists. , 2001, Bioorganic & medicinal chemistry letters.

[7]  M. Elices,et al.  Structure of the Integrin VLA‐4 and its Cell‐Cell and Cell‐Matrix Adhesion Functions , 1990, Immunological reviews.

[8]  S. Buchwald,et al.  An improved method for the palladium-catalyzed amination of aryl iodides. , 2001, The Journal of organic chemistry.

[9]  M. Maccoss,et al.  Substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl-phenylalanine analogues as potent VLA-4 antagonists. , 2002, Bioorganic & medicinal chemistry letters.

[10]  S. Buchwald,et al.  A Simple Catalytic Method for the Conversion of Aryl Bromides to Arylamines , 1995 .

[11]  马大为,et al.  Accelerating effect induced by the structure of αamino acid in the copper-catalyzed coupling reaction of aryl halides with α-amino acids. Synthesis of benzolactam-V8 , 1998 .

[12]  A. Morley,et al.  Diamine containing VLA-4 antagonists. , 2001, Bioorganic & medicinal chemistry.

[13]  C. Moody,et al.  Novel quinolinequinone antitumor agents: structure-metabolism studies with NAD(P)H:quinone oxidoreductase (NQO1). , 1999, Bioorganic & medicinal chemistry letters.

[14]  J. Tilley,et al.  N-benzylpyroglutamyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists. , 2000, Bioorganic & medicinal chemistry letters.

[15]  K. Luk,et al.  N-acyl phenylalanine analogues as potent small molecule VLA-4 antagonists. , 2000, Bioorganic & medicinal chemistry letters.

[16]  S. Buchwald,et al.  Simple, efficient catalyst system for the palladium-catalyzed amination of aryl chlorides, bromides, and triflates. , 2000, The Journal of organic chemistry.

[17]  R. Lobb,et al.  Chapter 18. Inhibitors of Integrin Alpha 4 Beta 1 (VLA-4) , 1999 .