Simple structure-based approach for predicting the activity of inhibitors of beta-secretase (BACE1) associated with Alzheimer's disease.

Beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) is a target of interest for treating patients with Alzheimer's disease (AD). Inhibition of BACE1 may prevent amyloid-ß (Aß) plaque formation and the development or progression of Alzheimer's disease. Known BACE1 inhibitors were analyzed using computational chemistry and cheminformatics techniques to search for quantitative structure-activity relationships (QSAR).

Exploration of the conformational space of a polymeric material that inhibits human immunodeficiency virus.

Baertschi et al. (Antiviral Chem. Chemother.

Evaluation of computational chemistry methods: crystallographic and cheminformatics analysis of aminothiazole methoximes.

Cheminformatics is used to validate the capabilities of widely used quantum chemistry and molecular mechanics methods. Among the quantum methods examined are the semiempirical MNDO, AM1, and PM3 methods, Hartree-Fock (ab initio) at a range of basis set levels, density functional theory (DFT) at a range of basis sets, and a post-Hartree-Fock method, local Moller-Plesset second-order perturbation theory (LMP2). Among the force fields compared are AMBER, MMFF94, MMFF94s, OPLS/A, OPLS-AA, Sybyl, and Tripos.

Synthesis, conformational analysis, and biological activity of new analogues of thiazole-4-carboxamide adenine dinucleotide (TAD) as IMP dehydrogenase inhibitors.

Thiazole-4-carboxamide adenine dinucleotide (TAD) analogues T-2'-MeAD (1) and T-3'-MeAD (2) containing, respectively, a methyl group at the ribose 2'-C-, and 3'-C-position of the adenosine moiety, were prepared as potential selective human inosine monophosphate dehydrogenase (IMPDH) type II inhibitors. The synthesis of heterodinucleotides was carried out by CDI-catalyzed coupling reaction of unprotected 2'-C-methyl- or 3'-C-methyl-adenosine 5'-monophosphate with 2',3'-O-isopropylidene-tiazofurin 5'-monophosphate, and then deisopropylidenation. Biological evaluation of dinucleotides 1 and 2 as inhibitors of recombinant human IMPDH type I and type II resulted in a good activity.