317364-40-2

Upstream product

• 3320-83-0 o-chlorophenyl isocyanate 
• 101349-30-8 methyl 4-amino-3-chlorobenzene-1-acetate 
• 1878-65-5 3-chlorophenylacetic acid 
• 97522-06-0 methyl (3-chloro-4-nitrophenyl)acetate 
• 53088-68-9 methyl 3-chlorophenylacetate 

Downstream Products

• 317364-41-3 (3-chloro-4-[N'-(2-chlorophenyl)ureido]phenyl)acetic acid 
• 317364-42-4 C₂₈H₂₆Cl₂FN₃O₅ 

Relevant academic research and scientific papers

Synthesis and biological evaluation of benzoic acid derivatives as potent, orally active VLA-4 antagonists

A series of benzoic acid derivatives was synthesized as VLA-4 antagonists. Introduction of chlorine or bromine into the 3-position on the central benzene of the diphenylurea portion as in lead compound 2 led to improvement in the pharmacokinetic properties. In particular, 12l demonstrated an acceptable plasma clearance and bioavailability in mice and rats as well as dogs (mice, CL = 18.5 ml/min/kg, F = 28 %; rats, CL = 5.2 ml/min/kg, F = 36 %; dogs, CL = 3.6 ml/min/kg, F = 55 %). Additionally, 12l exhibited potent activity with an IC50 value of 0.51 nM and efficacy by oral administration at a dosage of 10 mg/kg in a rat pleurisy model.

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.