185563-91-1Relevant articles and documents
Isoxazolines as potent antagonists of the integrin α(v)β3
Pitts, William J.,Wityak, John,Smallheer, Joanne M.,Tobin, A. Ewa,Jetter, James W.,Buynitsky, Jennifer S.,Harlow, Patricia P.,Solomon, Kimberly A.,Corjay, Martha H.,Mousa, Shaker A.,Wexler, Ruth R.,Jadhav, Prabhakar K.
, p. 27 - 40 (2007/10/03)
Starting with lead compound 2, we sought to increase the selectivity for α(v)β3-mediated cell adhesion by examining the effects of structural changes in both the guanidine mimetic and the substituent α to the carboxylate. To prepare some of the desired aminoimidazoles, a novel reductive amination utilizing a trityl-protected aminoimidazole was developed. It was found that guanidine mimetics with a wide range of pK(a)'s were potent antagonists of α(v)β3. In general, it appeared that an acylated 2-aminoimidazole guanidine mimetic imparted excellent selectivity for α(v)β3-mediated adhesion versus α(IIb)β3-mediated platelet aggregation, with selectivity of approximately 3 orders of magnitude observed for compounds 3g and 3h. It was also found in this series that the α- substituent was required for potent activity and that 2,6-disubstituted arylsulfonamides were optimal. In addition, the selective α(v)β3 antagonist 3h was found to be a potent inhibitor of α(v)β3-mediated cell migration.
