152954-92-2Relevant articles and documents
N-aryl-prolyl-dipeptides as potent antagonists of VLA-4.
Kamenecka, Theodore M,Lanza Jr., Thomas,de Laszlo, Stephen E,Li, Bing,McCauley, Ermengilda D,Van Riper, Gail,Egger, Linda A,Kidambi, Usha,Mumford, Richard A,Tong, Sharon,MacCoss, Malcolm,Schmidt, John A,Hagmann, William K
, p. 2205 - 2208 (2002)
The design, synthesis, and biological evaluation of N-arylprolyl-dipeptide derivatives as small molecule VLA-4 antagonists is described. Potency against VLA-4 and alpha(4)beta(7) and rat pharmacokinetic evaluation revealed some advantages over the related N-(arylsulfonyl)-prolyl-dipeptide analogues.
Macrocyclic prolinyl acyl guanidines as inhibitors of β-secretase (BACE)
Boy, Kenneth M.,Guernon, Jason M.,Wu, Yong-Jin,Zhang, Yunhui,Shi, Joe,Zhai, Weixu,Zhu, Shirong,Gerritz, Samuel W.,Toyn, Jeremy H.,Meredith, Jere E.,Barten, Donna M.,Burton, Catherine R.,Albright, Charles F.,Good, Andrew C.,Grace, James E.,Lentz, Kimberley A.,Olson, Richard E.,Macor, John E.,Thompson, Lorin A.
, p. 5040 - 5047 (2015/11/09)
The synthesis, evaluation, and structure-activity relationships of a class of acyl guanidines which inhibit the BACE-1 enzyme are presented. The prolinyl acyl guanidine chemotype (7c), unlike compounds of the parent isothiazole chemotype (1), yielded compounds with good agreement between their enzymatic and cellular potency as well as a reduced susceptibility to P-gp efflux. Further improvements in potency and P-gp ratio were realized via a macrocyclization strategy. The in vivo profile in wild-type mice and P-gp effects for the macrocyclic analog 21c is presented.
