Synthesis of potent and highly selective nonguanidine azetidinone inhibitors of human tryptase |
| |
Authors: | 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 |
| |
Institution: | The Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA. gregory.bisacchi@bms.com |
| |
Abstract: | 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 (IC(50)=1.8 nM), which has excellent selectivity against trypsin and most other related serine proteases. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|