Irreversible 4-Aminopiperidine Transglutaminase 2 Inhibitors for Huntington's Disease
作者
PRIME MICHAEL E; BROOKFIELD FREDERICK A; COURTNEY STEPHEN M; GAINES SIMON; MARSTON RICHARD W; ICHIHARA OSAMU; LI MARIE; VAIDYA DARSHAN; WILLIAMS HELEN; PEDRETDUNN ANNA; REED LAURA; SCHAERTL SABINE; TOLEDOSHERMAN LETICIA; BECONI MARIA; MACDONALD DOUGLAS; MUNOZSANJUAN IGNACIO; DOMINGUEZ CELIA; WITYAK JOHN
[摘要]：A new series of potent TG2 inhibitors are reported that employ a 4-aminopiperidine core bearing an acrylamide warhead. We establish the structure activity relationship of this new series and report on the transglutaminase selectivity and in vitro ADME properties of selected compounds. We demonstrate that the compounds do not conjugate glutathione in an in vitro setting and have superior plasma stability over our previous series.
