Microscale Parallel Synthesis of Acylated Aminotriazoles Enabling the Development of Factor XIIa and Thrombin Inhibitors.

Herein we report a microscale parallel synthetic approach allowing for rapid access to libraries of N-acylated aminotriazoles and screening of their inhibitory activity against factor XIIa (FXIIa) and thrombin, which are targets for antithrombotic drugs. This approach, in combination with post-screening structure optimization, yielded a potent 7 nM inhibitor of FXIIa and a 25 nM thrombin inhibitor; both compounds showed no inhibition of the other tested serine proteases. Selected N-acylated aminotriazoles exhibited anticoagulant properties in vitro influencing the intrinsic blood coagulation pathway, but not extrinsic coagulation. Mechanistic studies of FXIIa inhibition suggested that synthesized N-acylated aminotriazoles are covalent inhibitors of FXIIa. These synthesized compounds may serve as a promising starting point for the development of novel antithrombotic drugs.

A facile sonochemical protocol for synthesis of 3-amino- and 4-amino-1,2,4-triazole derived Schiff bases as potential antibacterial agents.

A facile method has been developed for the synthesis of Schiff bases derived from substituted and unsubstituted 3-amino- and 4-amino-1,2,4-triazoles. Condensation of the aminotrizoles with a variety of aromatic aldehydes afforded desired Schiff bases in excellent yields in 3-5 minutes of exposure to ultra-sound. The synthesized compounds were characterized by means of IR, 1HNMR and Mass spectrometry. The synthesized compounds were also screened for their antibacterial potential against Gram-negative (Escherichia coli, Shigella sonnei, Pseudomonas aeruginosa and Salmonella typhi) and two Gram-positive (Staphylococcus aureus and Bacillus subtilis) strains.

Synthesis and application of amino triazolium-modified lactobionic acid as chiral selector in capillary electrophoresis.

In this paper, a chiral selector, N-(4-H-1, 2, 4-triazolium)-lactobionamides (LA-ATM), was synthesized and applied for enantioseparation in capillary electrophoresis (CE) for the first time. Compared with lactobionic acid (LA) separation system, enhanced enantioseparation of five tested drugs was achieved in this modification system. In order to achieve good chiral separation, several parameters such as chiral selector concentration, buffer pH, applied voltage as well as the type and proportion of organic modifier were systematically investigated. Molecular modeling was applied to demonstrate the chiral recognition mechanism of the LA-ATM, which well supported the experimental results. Furthermore, a mathematical equation built up based on the molecular mechanics calculations was used in predicting resolution of tested drugs using LA or LA-ATM mediated CE, the predicted result was well correlated with the experimental result.

Efficient methodology for the synthesis of 3-amino-1,2,4-triazoles.

A general and efficient method for the preparation of 3-amino-1,2,4-triazoles has been developed. The desired 3-amino-1,2,4-triazoles (1) were prepared in good overall yield via two convergent routes. The key intermediate within both routes is substituted hydrazinecarboximidamide derivative 2.

Synthesis of tetrazole ribonucleosides and their evaluation as antiviral agents. 2. 5-Amino-1-(beta-D-ribofuranosyl)-1H-tetrazole and 5-amino-2-(beta-D-ribofuranosyl)-2H-tetrazole.

Synthesis of 5-amino-1-(beta-D-ribofuranosyl)-1H-tetrazole and 5-amino-2-(beta-D-ribofuranosyl)-2H-tetrazole is described. X-Ray crystallography was first used to establish the stereochemical configuration of the two isomers. By conducting 13C NMR analysis on these isomers with known structures, i.e., N1beta, a correlation is developed for determining the N-ribosyl attachment site of tetrazole ribonucleosides. Results are also presented on antiviral testing of these synthetic 5-aminotetrazole ribonucleosides against influenza A2/Asian/J305 virus infection in mice.