No abstract

Peptidomimetics represent an important field in chemistry, pharmacology and material science as they circumvent the limitations of traditional peptides used in therapy. Self-structural organizations such as turns, helices, sheets and loops can be accessed by chemical modifications of amino acids or peptides. In-depth structural and conformational analysis and structure-activity relationships (SAR) offer a way to establish peptidomimetic libraries. Herein, we review recent developments in peptidomimetics that are formed via heteroatom replacement within the native amino acid backbone. Each sub-section describes structural features, utility and preparative methods.

The influence of tautomerism on the precise structure of drugs and thus of their potential to interact with biological systems is discussed from thermodynamic and kinetic aspects. The types of tautomerism encountered in the structure of drugs in current use are surveyed together with the effect of pH, solvent polarity, and temperature.

Mosquito repellency data on acylpiperidines derived from the U.S. Department of Agriculture archives were modeled by using molecular descriptors calculated by CODESSA PRO software. An artificial neural network model was developed for the correlation of these archival results and used to predict the repellent activity of novel compounds of similar structures. A series of 34 promising N-acylpiperidine mosquito repellent candidates (4a-4q) were synthesized by reactions of acylbenzotriazoles 2a-2p with piperidines 3a-3f. Compounds (4a-4q) were screened as topically applied mosquito repellents by measuring the duration of repellency after application to cloth patches worn on the arms of human volunteers. Some compounds that were evaluated repelled mosquitoes as much as three times longer than N,N-diethyl-m-toluamide (DEET), the most widely used repellent throughout the world. The newly measured durations of repellency were used to obtain a superior correlation equation relating mosquito repellency to molecular structure.N-acylpiperidine ͉ quantitative structure-activity relationship ͉ CODESSA PRO ͉ artificial neural network ͉ Aedes aegypti

Acyl-, aroyl-, and heteroaroyl-acetic esters 6a-f and 8a-l are prepared by reactions of 1-acylbenzotriazoles 1a-k with acetoacetic esters 5 or 7a,b in the presence of sodium hydride followed by regioselective deacetylation. Similar C-acylation/deacetylation of acetylacetone and benzoylacetone affords beta-diketones 10a-d and 13a-c, respectively.