317357-42-9

Usage

Chemical Properties

White powder

Upstream product

• 317357-41-8 methyl 1-(tert-butoxycarbonyl)-(4S)-(2-naphthyloxy)-(2S)-pyrrolidinylcarboxylate 
• 74844-91-0 1-tert-butyl 2-methyl (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate 
• 135-19-3 β-naphthol 

Downstream Products

• 317357-45-2 methyl 4-[(4S)-(2-naphthyloxy)-(2S)-pyrrolidinyl]methoxybenzoate 
• 317357-44-1 methyl 4-[1-tert-butoxycarbonyl-(4S)-(2-naphthyloxy)-(2S)-pyrrolidinylmethoxy]benzoate 
• 317357-46-3 methyl 4-[(2S,4S)-1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-4-(2-naphthyloxy)-2-pyrrolidinyl]methoxybenzoate 

Relevant academic research and scientific papers

Synthesis, biological evaluation, and pharmacokinetic study of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives as VLA-4 antagonists

A series of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives were synthesized and evaluated for their activity as VLA-4 antagonists. Of 22 compounds synthesized, 19 compounds showed potent activity with low nanomolar IC50 values. In addition, the representative compounds 11o and 11p with a hydroxy group in the pyrrolidine ring showed moderate plasma clearance in rats (11o, 30 ml/min/kg and 11p, 21 ml/min/kg) and in dogs (11o, 12 ml/min/kg and 11p, 9 ml/min/kg).

VLA-4 inhibitor compounds

Compounds that selectively inhibit the binding of ligands to alpha4beta1 integrin (VLA-4) and methods for their preparation are disclosed. In one embodiment, compounds of the invention are represented by Formula I: As selective inhibitors of VLA-4 mediated cell adhesion, compounds of the present invention are useful in the treatment of conditions associated with such adhesion, including, but not limited to, such conditions as inflammatory and autoimmune responses, diabetes, asthma, psoriasis, inflammatory bowel disease, transplantation rejection, and tumor metastasis. Also disclosed are pharmaceutical compositions, methods of inhibiting VLA-4 mediated cell adhesion and methods of treating conditions associated with LA-4 mediated cell adhesion, which involve compounds of Formula I.

VLA-4 INHIBITORS

The present invention relates to a compound represented by the following formula (I): (wherein, W represents WA-A1 -WB - (in which, WA is substituted or unsubstituted aryl, etc., A1 is -NR1-, single bond, -C(O)-, etc., and WB is substituted or unsubstituted arylene, etc.), R is single bond, -NH-, -OCH2-, alkenylene, etc., X is -C(O) -CH2-, etc., and M is, for example, the following formula: (in which, R11, R12 and R13 each independently represents hydrogen, hydroxyl, amino, halogen, etc., R14 is hydrogen or lower alkyl, Y represents -CH2-O-, etc., Z is substituted or unsubstituted arylene, etc., A2 is single bond, etc, and R10 is hydroxyl or lower alkoxy)), or salt thereof; and a medicament containing the same. This compound or salt thereof selectively inhibits binding of cell adhesion molecules to VAL-4 and exhibits high bioavailability so that it is useful as a preventive and/or remedy for inflammatory diseases, autoimmune diseases, metastasis, bronchial asthma, rhinostenosis, diabetes, and the like.