The utility of clinically available antifungals is limited by their narrow spectrum of activity, high toxicity, and emerging resistance. Antifungal drug discovery has always been a challenging area, since fungi and their human host are eukaryotes, making it difficult to identify unique targets for antifungals. Novel antifungals in clinical development include first-in-class agents, new structures for an established target, and formulation modifications to marketed antifungals, in addition to repurposed agents. Membrane interacting peptides and aromatherapy are gaining increased attention in the field. Immunotherapy is another promising treatment option, with antifungal antibodies advancing into clinical trials. Novel targets for antifungal therapy are also being discovered, allowing the design of new promising agents that may overcome the resistance issue. In this mini review, we will summarize the current status of antifungal drug pipelines in clinical stages, and the most recent advancements in preclinical antifungal drug development, with special focus on their chemistry.

Pyrazine is a member of 1,4-diazines, which constitute an important class of heterocycles. Various pyrazine derivatives have been synthesized and successfully evaluated as agents with diverse pharmacological effects (including but not limited to antiproliferative, anti-infective, and effects on cardiovascular or nervous system) and some of them have become clinically used drugs worldwide. This review is a survey of important patents on pyrazine derivatives with pharmacological activity published in the period June 2012 - July 2014. The patent databases SciFinder and esp@cenet were used to locate patent applications. Pyrazine derivatives possess numerous noteworthy pharmacological effects, including antimycobacterial, antibacterial, antifungal, antidiabetic, diuretic, anticancer, antiviral, hypnotic, and analgesic. The class of pyrazine-based candidate drugs has experienced a rapid growth both in absolute numbers of investigated compounds and in the spectrum of diverse biological activities. We expect that several of these compounds will add to existing pharmaceuticals in the very near future. According to the number of compounds and filed patents, the most promising areas are: i) inhibitors of protein kinases (applicable as antiproliferatives); and ii) inhibitors of β-secretase (applicable for the treatment of Alzheimer's disease).

The reactivators of acetylcholinesterase are very important components in the treatment of intoxications caused by organophosphate inhibitors such as tabun, sarin, soman, VX etc. and insecticides like echothiofat, metrifonat, chlorpyrifos etc. These inhibitors covalently bind on active site of mentioned enzyme and irreversibly inhibit its activity. The reactivator breaks the inhibitor-enzyme covalent bond and restores its activity. Unfortunately, there is no reactivator applicable for every type of inhibition; it means that every structural change in the molecule of inhibitor needs a specific structure of the reactivator. Therefore, development of more active acetylcholinesterase reactivators with broader spectrum is a major challenge actual from the point of view of war operations, accidents or terroristic attacks. Synthetic approaches, biological activity evaluation and structure-activity relationship studies of newly prepared acetylcholinesterase reactivators from 1990 to 2004 are summarized. Synthetic procedures used and the evaluation of antidotal efficacies are mentioned for individual types of reactivators. The main attention was paid to reactivators derived from pyridine carbaldoxime and imidazole carbaldoxime.