155541-67-6Relevant articles and documents
Discovery of 2-aminothiazole-4-carboxamides, a novel class of muscarinic M3 selective antagonists, through solution-phase parallel synthesis
Sagara, Yufu,Mitsuya, Morihiro,Uchiyama, Minaho,Ogino, Yoshio,Kjmura, Toshifumi,Ohtake, Norikazu,Mase, Toshiaki
, p. 437 - 440 (2007/10/03)
Synthesis and structure-activity relationship of a new class of muscarinic M3 selective antagonists were described. In the course of searching for a muscarinic M3 antagonist with a structure distinct from those of the 2-(4,4-difluorocyclopentyl)-2-phenylacetamide derivatives, we identified a thiazole-4-carboxamide derivative (1) as a lead compound in our in-house chemical collection. Since this compound (1) showed relatively low binding affinity (K1 = 140 nM) for M3 receptors in the human binding assays, we tried to improve its potency and selectivity for M 3 over M1 and M2 receptors by derivatization of 1 through a combinatorial approach. A solution-phase parallel synthesis effectively contributed to the optimization of each segment of 1. Thus, we have identified a cyclooctenylmethyl derivative (3e) and a cyclononenylmethyl derivative (3f) as representative M3 selective antagonists in this class.
Design and synthesis of potent and highly selective thrombin inhibitors
Hilpert,Ackermann,Banner,Gast,Gubernator,Hadvary,Labler,Muller,Schmid,Tschopp,Van de Waterbeemd
, p. 3889 - 3901 (2007/10/02)
Thrombin, a serine protease, plays a central role in the initiation and propagation of thrombotic events. An extensive search for new thrombin inhibitors was performed, using an unconventional approach. Screening of small basic molecules for binding in th
