942056-42-0Relevant articles and documents
Preparation and biological evaluation of BACE1 inhibitors: Leveraging trans-cyclopropyl moieties as ligand efficient conformational constraints
Audia, James E.,Barberis, Mario,Beck, James P.,Boggs, Leonard N.,Borders, Anthony R.,Boyer, Robert D.,Brier, Richard A.,Erickson, Jon A.,Garcia-Losada, Pablo,Green, Steven J.,Hembre, Erik J.,Hendle, J?rg,Lopez, Jose E.,Mathes, Brian M.,May, Patrick C.,Mergott, Dustin J.,Minguez, Jose Miguel,Monk, Scott A.,Porter, Warren J.,Rankovic, Zoran,Shi, Yuan,Stout, Stephanie L.,Timm, David E.,Watson, Brian M.,Winneroski, Leonard L.,Yang, Zhixiang
, (2019/12/09)
Inhibition of BACE1 has become an important strategy in the quest for disease modifying agents to slow the progression of Alzheimer's disease. We previously reported the fragment-based discovery of LY2811376, the first BACE1 inhibitor reported to demonstrate robust reduction of human CSF Aβ in a Phase I clinical trial. We also reported on the discovery of LY2886721, a potent BACE1 inhibitor that reached phase 2 clinical trials. Herein we describe the preparation and structure activity relationships (SAR) of a series of BACE1 inhibitors utilizing trans-cyclopropyl moieties as conformational constraints. The design, details of the stereochemically complex organic synthesis, and biological activity of these BACE1 inhibitors is described.
Synthesis of 3-oxooxa- and 3-oxoazacycloalk-4-enes by ring-closing metathesis. Application to the synthesis of an inhibitor of cathepsin K
Taillier, Catherine,Hameury, Thomas,Bellosta, Véronique,Cossy, Janine
, p. 4472 - 4490 (2008/02/01)
3-Oxooxa- and 3-oxoazacycloalk-4-enes were obtained with good yield from 1-(ω-alkenyloxy)- and 1-(ω-alkenylamino)-but-3-en-2-ones by using a ring-closing metathesis. This methodology has been used to synthesize an inhibitor of cathepsin K.
