34577-30-5Relevant academic research and scientific papers
Tripeptidic BACE1 inhibitors devised by in-silico conformational structure-based design
Hamada, Yoshio,Tagad, Harichandra D.,Nishimura, Yoshinori,Ishiura, Shoichi,Kiso, Yoshiaki
, p. 1130 - 1135 (2012/03/26)
Previously reported pentapeptidic BACE1 inhibitors, designed using a substrate-based approach, were used as lead compounds for the further design of non-peptidic BACE1 inhibitors. Although these peptidic and non-peptidic inhibitors, with a hydroxymethylcarbonyl isostere as a substrate transition-state mimic, exhibited potent BACE1 inhibitory activities, their molecular-sizes appeared a little too big (molecular weight of >600 daltons) for developing practical anti-Alzheimer's disease drugs. To develop lower weight BACE1 inhibitors, a series of tripeptidic BACE1 inhibitors were devised using a design approach based on the conformation of a virtual inhibitor bound to the BACE1 active site, also called 'in-silico conformational structure-based design'. Although these tripeptidic BACE1 inhibitors contained some natural amino acid residues, they are expected to be useful as lead compounds for developing the next generation BACE1 inhibitors, due to their low molecular size and unique structural features compared with previously reported inhibitors.
Pd(II)-catalyzed hydroxyl-directed C-H olefination enabled by monoprotected amino acid ligands
Lu, Yi,Wang, Dong-Hui,Engle, Keary M.,Yu, Jin-Quan
supporting information; experimental part, p. 5916 - 5921 (2010/07/05)
A novel Pd(II)-catalyzed ortho-C-H olefination protocol has been developed using spatially remote, unprotected tertiary, secondary, and primary alcohols as the directing groups. Mono-N-protected amino acid ligands were found to promote the reaction, and an array of olefin coupling partners could be used. When electron-deficient alkenes were used, the resulting olefinated intermediates underwent subsequent Pd(II)-catalyzed oxidative intramolecular cyclization to give the corresponding pyran products, which could be converted into ortho-alkylated alcohols under hydrogenolysis conditions. The mechanistic details of the oxidative cyclization step are discussed and situated in the context of the overall catalytic cycle.
Use of 5-hydroxy-4H-benzo[1,4]oxazin-3-ones as β2-adrenoceptor agonists
Hoenke, Christoph,Bouyssou, Thierry,Tautermann, Christofer S.,Rudolf, Klaus,Schnapp, Andreas,Konetzki, Ingo
scheme or table, p. 6640 - 6644 (2010/06/12)
Novel β2-agonists with a 5-hydroxy-4H-benzo[1,4]oxazin-3-one moiety as head group are described. Systematic chemical variations at the phenethylamine residue of these compounds lead to the discovery of compound 6m as potent, full agonist of the β2-adrenoceptor with a high β1/β2-selectivity. Molecular modeling revealed an interaction between the carboxylic acid group of 6m and a lysine residue (K305) of the β2-receptor as putative explanation for the high observed selectivity. Further, compound 6m displayed in a guinea pig in vivo model a complete reversal of acetylcholine induced bronchoconstriction which lasted over the complete study time of 5 h.
