1142865-30-2Relevant academic research and scientific papers
Structure-based design and synthesis of macrocyclic peptidomimetic β-secretase (BACE-1) inhibitors
Machauer, Rainer,Veenstra, Siem,Rondeau, Jean-Michel,Tintelnot-Blomley, Marina,Betschart, Claudia,Neumann, Ulf,Paganetti, Paolo
, p. 1361 - 1365 (2009)
The hydroxyethylene octapeptide inhibitor OM99-2 served as starting point to create the tripeptide inhibitor 1 and its analogues 2a and b. An X-ray co-crystal structure of 1 with BACE-1 allowed the design and syntheses of a series of macrocyclic analogues 3a-h covalently linking the P1 and P3 side-chains. These inhibitors show improved enzymatic potency over their open-chain analogue. Inhibitor 3h also shows activity in a cellular system.
MACROCYCLIC LACTAMS AND PHARMACEUTICAL USE THEREOF
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Page/Page column 31, (2008/06/13)
The present invention relates to novel macrocyclic compounds of the formula (I) wherein R1, R2, R3, U, V, W, X, Y, Z and n are as defined in the specification, the number of ring atoms included in the macrocyclic ring being 14, 15, 16 or 17, in free base form or in acid addition salt form, to their preparation, to their use as pharmaceuticals and to pharma-ceutical compositions comprising them.
