226066-04-2Relevant 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 (2002)
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.
Highly constrained bicyclic VLA-4 antagonists
Chang, Linda L.,Truong, Quang,Doss, George A.,MacCoss, Malcolm,Lyons, Kathryn,McCauley, Ermengilda,Mumford, Richard,Forrest, Gail,Vincent, Stella,Schmidt, John A.,Hagmann, William K.
, p. 597 - 601 (2008/02/05)
VLA-4 is implicated in several inflammatory and autoimmune disease states. A series of cyclic β-amino acids (β-aa) was studied as VLA-4 antagonists. Binding affinity was highly dependent on the dihedral angle (φ{symbol}) between the amino and the carboxyl
