225517-69-1

Upstream product

• 705-21-5 3,5-dichlorobenzensulfonyl chloride 

Downstream Products

• 425388-74-5 (S)-2-{[(S)-1-(3,5-Dichloro-benzenesulfonyl)-2-methyl-pyrrolidine-2-carbonyl]-amino}-3-(4-hydroxy-phenyl)-propionic acid methyl ester 
• 225517-68-0 (R)-3-{[(S)-1-(3,5-Dichloro-benzenesulfonyl)-2-methyl-pyrrolidine-2-carbonyl]-amino}-3-(2'-methoxy-biphenyl-4-yl)-propionic acid methyl ester 
• 217452-76-1 (S)-2-{[(S)-1-(3,5-Dichloro-benzenesulfonyl)-2-methyl-pyrrolidine-2-carbonyl]-amino}-3-phenyl-propionic acid 
• 217452-76-1 (R)-2-{[(S)-1-(3,5-Dichloro-benzenesulfonyl)-2-methyl-pyrrolidine-2-carbonyl]-amino}-3-phenyl-propionic acid 

Relevant academic research and scientific papers

INTEGRIN ANTAGONISTS

The present disclosure provides therapeutic agents including those of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such therapeutic agents. Methods of using the therapeutic agents are also provided.

The discovery of small molecule carbamates as potent dual α4β1/α4β7 integrin antagonists

The α4β1 and α4β7 integrins are implicated in several inflammatory disease states. Systematic SAR studies of an α4β1-specific arylsulfonyl-Pro-Tyr lead led to the identification of a new α4β7 binding site, best captured by O-carbamates of Tyr for this structural class. Several compounds showed a 200- to 400-fold improvement in α4β7 binding affinity while maintaining subnanomolar α4β1 activity, for example 2l, VCAM-Ig α4β1 IC50=0.13 nM, VCAM-Ig α4β7 IC50=1.92 nM.