425388-71-2Relevant academic research and scientific papers
The discovery of small molecule carbamates as potent dual α4β1/α4β7 integrin antagonists
Chang, Linda L.,Truong, Quang,Mumford, Richard A.,Egger, Linda A.,Kidambi, Usha,Lyons, Kathryn,McCauley, Ermengilda,Van Riper, Gail,Vincent, Stella,Schmidt, John A.,MacCoss, Malcolm,Hagmann, William K.
, p. 159 - 163 (2007/10/03)
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.
Substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl-phenylalanine analogues as potent VLA-4 antagonists
Kopka, Ihor E,Young, David N,Lin, Linus S,Mumford, Richard A,Magriotis, Plato A,MacCoss, Malcolm,Mills, Sander G,Riper, Gail Van,McCauley, Ermengilda,Egger, Linda E,Kidambi, Usha,Schmidt, John A,Lyons, Kathryn,Stearns, Ralph,Vincent, Stella,Colletti, Adria,Wang, Zhen,Tong, Sharon,Wang, Junying,Zheng, Song,Owens, Karen,Levorse, Dorothy,Hagmann, William K
, p. 637 - 640 (2007/10/03)
A series of substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl- and α-methyl-L-prolyl-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists. The compounds showed excellent potency with a wide variety of neutral, polar, electron withdrawing or donating groups on the phenylalanine ring (IC50～1 nM). Heteroaryl ring substitution for phenylalanine was also well tolerated. Pharmacokinetic studies in rat were performed on a representative set of compounds in both series.
