Five-membered 1,2,4-oxadiazole heterocyclic ring has received considerable attention because of its unique bioisosteric properties and an unusually wide spectrum of biological activities. Thus, it is a perfect framework for the novel drug development. After a century since the 1,2,4-oxadiazole have been discovered, the uncommon potential attracted medicinal chemists’ attention, leading to the discovery of a few presently accessible drugs containing 1,2,4-oxadiazole unit. It is worth noting that the interest in a 1,2,4-oxadiazoles’ biological application has been doubled in the last fifteen years. Herein, after a concise historical introduction, we present a comprehensive overview of the recent achievements in the synthesis of 1,2,4-oxadiazole-based compounds and the major advances in their biological applications in the period of the last five years as well as brief remarks on prospects for further development.
Histone deacetylases (HDACs) are a large family of epigenetic metalloenzymes that are involved in gene transcription and regulation, cell proliferation, differentiation, migration, and death, as well as angiogenesis. Particularly, disorders of the HDACs expression are linked to the development of many types of cancer and neurodegenerative diseases, making them interesting molecular targets for the design of new efficient drugs and imaging agents that facilitate an early diagnosis of these diseases. Thus, their selective inhibition or degradation are the basis for new therapies. This is supported by the fact that many HDAC inhibitors (HDACis) are currently under clinical research for cancer therapy, and the Food and Drug Administration (FDA) has already approved some of them. In this review, we will focus on the recent advances and latest discoveries of innovative strategies in the development and applications of compounds that demonstrate inhibitory or degradation activity against HDACs, such as PROteolysis-TArgeting Chimeras (PROTACs), tumor-targeted HDACis (e.g., folate conjugates and nanoparticles), and imaging probes (positron emission tomography (PET) and fluorescent ligands).
In the present work, we report convenient methods for the synthesis and biological evaluation of phosphate tricyclic coumarin derivatives as potential steroid sulfatase inhibitors.
In the present work, we report the initial results of our study on a series of 3-phenylcoumarin sulfamate-based compounds containing C-F bonds as novel inhibitors of steroid sulfatase. The new compounds are potent steroid sulfatase inhibitors, possessing more than 10 times higher inhibitory potency than coumarin-7-O-sulfamate. In the course of our investigation, compounds 2b and 2c demonstrated the highest inhibitory effect on the enzymatic steroid sulfatase assay; both had IC50 values of 0.27 μm (the IC50 value of coumarin-7-O-sulfamate is 3.5 μm, used as a reference).
This review summarizes the state of knowledge on the chemical methods of C(5)-modifications of uridine and cytidine derivatives and may serve as a useful tool for synthetic chemists to choose an appropriate reaction protocol. The synthesis of 5-substituted uracil derivatives is gaining an increasing interest because of their possible applications in medicine and pharmacy. Modifications at the C(5) position of pyrimidine nucleosides can enhance their biostability, bioavailability or(and) biological activity. Among the C(5)-modified nucleosides, 5-halopyrimidines exhibit anticancer, antiviral, radio- and photosensitizing properties. Besides 5-halo-substituted derivatives, there are other examples of nucleosides with confirmed biological activity containing a C–C bond at the C(5) position in the pyrimidine ring. In recent decades, scientists have achieved great progress in the field of cross-coupling reactions. Among them, nickel-catalyzed processes provide a broad spectrum of synthetic methods that are based on less toxic and cheaper starting materials. This review summarizes the synthetic approaches based on the coupling or halogenation reactions, which enable 5-substituted pyrimidine nucleosides to be obtained. Moreover, the importance of the systems considered for medicine and pharmacy is briefly discussed.
The bibliography includes 197 references.
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