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      Recent Advances in Synthesis and Properties of Pyrazoles

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      Chemistry
      MDPI AG

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          Abstract

          Pyrazole-containing compounds represent one of the most influential families of N-heterocycles due to their proven applicability and versatility as synthetic intermediates in preparing relevant chemicals in biological, physical-chemical, material science, and industrial fields. Therefore, synthesizing structurally diverse pyrazole derivatives is highly desirable, and various researchers continue to focus on preparing this functional scaffold and finding new and improved applications; this review highlights some of the most recent and strategic examples regarding the synthesis and properties of different pyrazole derivatives, mainly reported from 2017–present. The discussion involves strategically functionalized rings (i.e., amines, carbaldehydes, halides, etc.) and their use in forming various fused systems, predominantly bicyclic cores with 5:6 fusion taking advantage of our experience in this field and the more recent investigations of our research group.

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          Anion Recognition Strategies Based on Combined Noncovalent Interactions

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            Axitinib: A Review of its Safety and Efficacy in the Treatment of Adults with Advanced Renal Cell Carcinoma

            Over the last seven years, seven targeted agents have been approved in the treatment of advanced or metastatic renal cell cancer, changing the therapeutic approach and prognosis of the disease dramatically. The latest agent with demonstrated efficacy is axitinib (Inlyta®). This new generation of tyrosine kinase agent differs from previously existing agents by its greater activity potency of inhibition of vascular endothelial growth factor-receptor (VEGFR1-3). This efficacy has been tested in phase II and III clinical trials. Axitinib is the only targeted agent that benefits from recommended titration, with intra-patient dose escalation. The toxicity profile of the drug is tolerable. This paper reviews the mechanism of action of axitinib, its metabolism, and its pharmacokinetic profile. Clinical data of efficacy and safety is also detailed. The agent has been integrated in the international therapeutic guidelines, as a standard in treatment of renal cell cancer patients, previously treated through antiangiogenic therapy.
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              Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile dysfunction.

              Sildenafil citrate has been shown to be effective in a wide range of patients with erectile dysfunction and has been approved in the United States for this indication. The overall clinical safety of oral sildenafil, a potent inhibitor of phosphodiesterase type 5, in the treatment of erectile dysfunction was evaluated in more than 3700 patients (with a total of 1631 years of exposure worldwide). Safety and tolerability data were analysed from a series of double-blind, placebo-controlled studies and from 10 open-label extension studies of sildenafil in the treatment of erectile dysfunction. A total of 4274 patients (2722 sildenafil, 1552 placebo; age range 19-87 y) received double-blind treatment over a period of up to six months' duration, and 2199 received long-term, open-label sildenafil for up to 1 y. The most commonly reported adverse events (all causes) were headache (16% sildenafil, 4% placebo), flushing (10% sildenafil, 1% placebo), and dyspepsia (7% sildenafil, 2% placebo) and they were predominantly transient and mild or moderate in nature. These adverse events reflect the pharmacology of sildenafil as a phosphodiesterase type 5 inhibitor. No cases of priapism were reported. The rate of discontinuation due to adverse events (all causes) was comparable for patients treated with sildenafil (2.5%) and placebo (2.3%). In open-label extension studies, 90% of patients completed long-term sildenafil treatment, with only 2% withdrawing due to adverse events. Sildenafil is a well-tolerated oral treatment for erectile dysfunction.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                CBSHA6
                Chemistry
                Chemistry
                MDPI AG
                2624-8549
                September 2022
                August 29 2022
                : 4
                : 3
                : 940-968
                Article
                10.3390/chemistry4030065
                b980e47e-f6fc-416e-a8ec-576f92711675
                © 2022

                https://creativecommons.org/licenses/by/4.0/

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