Tetrazole derivatives are a prime class of heterocycles, very important to medicinal chemistry and drug design due to not only their bioisosterism to carboxylic acid and amide moieties but also to their metabolic stability and other beneficial physicochemical properties. Although more than 20 FDA-approved drugs contain 1 H- or 2 H-tetrazole substituents, their exact binding mode, structural biology, 3D conformations, and in general their chemical behavior is not fully understood. Importantly, multicomponent reaction (MCR) chemistry offers convergent access to multiple tetrazole scaffolds providing the three important elements of novelty, diversity, and complexity, yet MCR pathways to tetrazoles are far from completely explored. Here, we review the use of multicomponent reactions for the preparation of substituted tetrazole derivatives. We highlight specific applications and general trends holding therein and discuss synthetic approaches and their value by analyzing scope and limitations, and also enlighten their receptor binding mode. Finally, we estimated the prospects of further research in this field.

Tetrazoles via Multicomponent Reactions.

The properties of catenated nitrogen molecules, molecules containing internal chains of bonded nitrogen atoms, is of fundamental scientific interest in chemical structure and bonding, as nitrogen i...

Properties and Promise of Catenated Nitrogen Systems As High-Energy-Density Materials

Strecker reaction and α-amino nitriles: Recent advances in their chemistry, synthesis, and biological properties

This short review compiles the main results of the studies in tetrazole chemistry published in the period 2009–2016. Attention is directed to the structure, reactivity, synthetic problems, functionalization, and also to the application of derivatives of this class of polynitrogen heterocyclic compounds. New conditions are revealed of the tetrazole synthesis underpinned by the use of versatile catalytic systems, ionic liquids, superacids, microwave activation, microreactor techniques, etc. Main trends in the development of the tetrazole chemistry that are helping to focus the efforts of researchers on novel, important, and promising directions of study are considered.

Developments in Tetrazole Chemistry (2009–16)

A tetrazole derivative 1-[(1H-tetrazol-5-ylimino)methyl]naphthalen-2-ol (H2L) as a fluorescent chemosensor for Al3+ in DMSO and Zn2+ in DMF was designed and synthesized. From 1H NMR data, the Job plot and the ESI-MS spectrum, 1:1 stoichiometric complexation between H2L and Al3+/Zn2+ was found in DMSO and DMF, respectively. The theoretical calculations at the level of B3LYP/6-311G** for the ground state and TD-B3LYP/6-311G** for the excited state revealed the sensing mechanism is the inhibition of excited state intramolecular proton transfer (ESIPT). And the possible fluorescent species formed in the DMSO and DMF solutions were deduced to be [Al(HL)(OH)(NO3)(H2O)(DMSO)] and [Zn(HL)(OH)(H2O)(DMF)]. What's more, it is confirmed that H2L could be used to detect Al3+ and Zn2+ in cells by bioimaging.

A tetrazole-based fluorescence “turn-on” sensor for Al(III) and Zn(II) ions and its application in bioimaging

Properties of responsible for biological activity tetrazoles are considered. Examples are given of active pharmaceutical ingredients of modern drugs containing the tetrazole ring in the molecular structure. New publications on the synthesis and investigations of biological activity of promising tetrazole-containing compounds are cited.

Medicinal chemistry of tetrazoles

Review: biological and medicinal activity of tetrazole derivatives and tetrazole containing compounds; 124 refs.

R. E. Trifonov

Papers

Medicinal chemistry of tetrazoles

Medicinal Chemistry of Tetrazoles