NMR conformational analysis of a hydroxyethylamine peptide isostere developed as an aspartic protease inhibitor shows that it is a flexible architecture. Cyclization to form pyrrolidines, piperidines, or morpholines results in a preorganization of the whole system in solution. The resulting conformation is similar to the conformation of the inhibitor in the active site of BACE-1. This entropic gain results in increased affinity for the enzyme when compared with the acyclic system. For morpholines 27 and 29, the combination of steric and electronic factors is exploited to orient substituents toward S1, S1', and S2' pockets both in the solution and in the bound states. These highly preorganized molecules proved to be the most potent compounds of the series. Additionally, the morpholines, unlike the pyrrolidine and piperidine analogues, have been found to be brain penetrant BACE-1 inhibitors.
N-Bromosuccinimide as a Regioselective Nuclear Monobrominating Reagent for Phenols and Naphthols.-A variety of phenols or naphthols is regioselectively substituted at the para-OH position using NBS in acetonitrile, whereas in carbon disulfide mainly ortho-substituted products are obtained. -(CARRENO, M. C.; GARCIA RUANO, J. L.; SANZ, G.; TOLEDO, M. A.; URBANO, A.; Synlett
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Mild and Regiospecific Nuclear Iodination of Methoxybenzenes andNaphthalenes with N-Iodosuccinimide in Acetonitrile.-The aromatic iodo compounds, obtained in a regiospecific manner under mild conditions, are useful, e.g. for C-C-bond formation.-(CARRENO, M. C.; GARCIA RUANO, J. L.; SANZ, G.; TOLEDO, M. A.; URBANO, A.;
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.