705950-85-2Relevant academic research and scientific papers
Synthesis of potent and highly selective nonguanidine azetidinone inhibitors of human tryptase
Bisacchi, Gregory S.,Slusarchyk, William A.,Bolton, Scott A.,Hartl, Karen S.,Jacobs, Glenn,Mathur, Arvind,Meng, Wei,Ogletree, Martin L.,Pi, Zulan,Sutton, James C.,Treuner, Uwe,Zahler, Robert,Zhao, Guohua,Seiler, Steven M.
, p. 2227 - 2231 (2007/10/03)
Azetidinones such as BMS-363131 (2) and BMS-363130 (3), which contain a guanidine group in the C-3 side chain were previously shown to be very potent inhibitors of human tryptase with high selectivity versus other serine proteases, including trypsin. In this letter, we describe the discovery of a number of potent azetidinone tryptase inhibitors in which the guanidine moiety at the ring C-3 position is replaced with primary or secondary amine or aminopyridine functionality. In particular, BMS-354326 (4) is a highly potent tryptase inhibitor (IC50=1.8nM), which has excellent selectivity against trypsin and most other related serine proteases.
