Nitrogen-containing heterocyclic compounds and their derivatives have historically been invaluable as a source of therapeutic agents. Pyrazole, which has two nitrogen atoms and aromatic character, provides diverse functionality and stereochemical complexity in a five-membered ring structure. In the past decade, studies have reported a growing body of data on different pyrazole derivatives and their innumerable physiological and pharmacological activities. In part, such studies attempted to reveal the wide range of drug-like properties of pyrazole derivatives along with their structure–activity relationships in order to create opportunities to harness the full potentials of these compounds. Here, we summarize strategies to synthesize pyrazole derivatives and demonstrate that this class of compounds can be targeted for the discovery of new drugs and can be readily prepared owing to recent advances in synthetic medicinal chemistry.

Review: biologically active pyrazole derivatives

The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. Apart from the already marketed drugs, there are many other being investigated for their promising activity against several malignancies. In particular, anticancer research has been capitalizing on the intrinsic versatility and dynamic core scaffold of these compounds. Nevertheless, as for any other promising anticancer drugs, heterocyclic compounds do not come without shortcomings. In this review, we provide for a concise overview of heterocyclic active compounds and families and their main applications in medicine. We shall focus on those suitable for cancer therapy while simultaneously addressing main biochemical modes of action, biological targets, structure-activity relationships as well as intrinsic limitation issues in the use of these compounds. Finally, considering the advent of nanotechnology for effective selective targeting of drugs, we shall discuss fundamental aspects and considerations on nanovectorization of such compounds that may improve pharmacokinetic/pharmacodynamic properties of heterocycles.

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Heterocyclic Anticancer Compounds: Recent Advances and the Paradigm Shift towards the Use of Nanomedicine's Tool Box.

1,3,4-Thiadiazole: Synthesis, Reactions, and Applications in Medicinal, Agricultural, and Materials Chemistry

The 1,3,4-thiadiazole nucleus is one of the most important and well-known heterocyclic nuclei, which is a common and integral feature of a variety of natural products and medicinal agents. Thiadiazole nucleus is present as a core structural component in an array of drug categories such as antimicrobial, anti-inflammatory, analgesic, antiepileptic, antiviral, antineoplastic, and antitubercular agents. The broad and potent activity of thiadiazole and their derivatives has established them as pharmacologically significant scaffolds. In this study, an attempt has been made with recent research findings on this nucleus, to review the structural modifications on different thiadiazole derivatives for various pharmacological activities.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cbdd.12125

1,3,4-thiadiazole and its derivatives: a review on recent progress in biological activities.

Advances of azide-alkyne cycloaddition-click chemistry over the recent decade

Synthesis, antifungal activities and 3D-QSAR study of N-(5-substituted-1,3,4-thiadiazol-2-yl)cyclopropanecarboxamides

A series of trifluoromethyl-substituted 1,2,4-triazole Mannich base 6 and bis(1,2,4-triazole) Mannich base 7 containing pyrimidinylpiperazine rings via the Mannich reaction were synthesized and characterized by infrared (IR), 1H nuclear magnetic resonance (NMR), and elemental analysis. The fungicidal tests indicated that most of compounds 6 and 7 possessed excellent fungicidal activity. Among 19 novel compounds, some showed superiority over commercial fungicides Dimethomorph, Thiophanate-methyl, Iprodione, and Zhongshengmycin. Some compounds also exhibited favorable herbicidal activity in the preliminary studies. On the basis of the comparative molecular field analysis (CoMFA), five novel compounds were subsequently synthesized, their activities were estimated fairly accurately, and compounds 6-A1 and 7-A2 displayed good fungicidal activity against Pseudoperonospora cubensis (96.9 and 84.9%) as 6h and 7c, respectively.

Synthesis and biological activity of some novel trifluoromethyl-substituted 1,2,4-triazole and bis(1,2,4-triazole) Mannich bases containing piperazine rings.

Synthesis and antiviral activity of new acrylamide derivatives containing 1,2,3-thiadiazole as inhibitors of hepatitis B virus replication.

Synthesis, bioactivity, theoretical and molecular docking study of 1-cyano-N-substituted-cyclopropanecarboxamide as ketol-acid reductoisomerase inhibitor.

A series of cycloadducts--pyrazoles via 1,3-dipolar cycloaddition reactions of generated nitrilimines with N-(4-chloro-2-fluorophenyl)maleimide were described. The novel compounds synthesized were characterized by (1)H NMR, MS, and elemental analysis. The fungicidal tests showed that most of the title compounds exhibit significant fungicidal activities against Corynespora cassiicola.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1747-0285.2010.00948.x

Xing-Hai Liu

Papers

Synthesis, antifungal activities and 3D-QSAR study of N-(5-substituted-1,3,4-thiadiazol-2-yl)cyclopropanecarboxamides

Synthesis and biological activity of some novel trifluoromethyl-substituted 1,2,4-triazole and bis(1,2,4-triazole) Mannich bases containing piperazine rings.

Synthesis and antiviral activity of new acrylamide derivatives containing 1,2,3-thiadiazole as inhibitors of hepatitis B virus replication.

Synthesis, bioactivity, theoretical and molecular docking study of 1-cyano-N-substituted-cyclopropanecarboxamide as ketol-acid reductoisomerase inhibitor.

Synthesis and antifungal activities of new pyrazole derivatives via 1,3-dipolar cycloaddition reaction.