【文章名】Cyclic Hydroxyamidines as Amide Isosteres: Discovery of Oxadiazolines and Oxadiazines as Potent and Highly Efficacious gamma-Secretase Modulators in Vivo
Cyclic Hydroxyamidines as Amide Isosteres: Discovery of Oxadiazolines and Oxadiazines as Potent and Highly Efficacious gamma-Secretase Modulators in Vivo
作者
SUN ZHONGYUE; ASBEROM THEODROS; BARA THOMAS; BENNETT CHAD; BURNETT DUANE; CHU INHOU; CLADER JOHN; COHENWILLIAMS MARY; COLE DAVID; CZARNIECKI MICHAEL; DURKIN JAMES; GALLO GIOCONDA; GREENLEE WILLIAM; JOSIEN HUBERT; HUANG XIANHAI; HYDE LYNN; JONES NICHOLAS; KAZAKEVICH IRINA; LI HONGMEI; LIU XIAOXIANG; LEE JULIE; MACCOSS MALCOLM; MANDAL MIHIR B; MCCRACKEN TROY; NOMEIR AMIN; MAZZOLA ROBERT; PALANI ANANDAN; PARKER ERIC M; PISSARNITSKI DMITRI A; QIN JUN; SONG LIXIN; TERRACINA GIUSEPPE; VICAREL MONICA; VOIGT JOHANNES; XU RUO; ZHANG LILI; ZHANG QI; ZHAO ZHIQIANG; ZHU XIAOHONG; ZHU ZHAONING
[摘要]：Cyclic hydroxyamidines were designed and validated as isosteric replacements of the amide functionality. Compounds with these structural motifs were found to be metabolically stable and to possess highly desirable pharmacokinetic profiles. These designs were applied in the identification of gamma-secretase modulators leading to highly efficacious agents for reduction of central nervous system A beta(42) in various animal models.
