Isoxazoles are a class of heterocyclic compounds having a remarkable number of applications and have been demonstrated to be very versatile building blocks in organic synthesis. The wide range of biological activities includes pharmacological properties such as hypoglycemic, analgesic, antiinflammatory, anti-bacterial and HIV-inhibitory activity. Some isoxazole derivatives display agrochemical properties namely herbicidal and soil fungicidal activity and have applications as pesticides and insecticides. Isoxazoles have also been used as dyes, electric insulating oils, high temperature lubricants and polyisoxazoles have applications as semicondutors. The key feature of these heterocycles is that they possess the typical properties of an aromatic system but contain a weak nitrogen-oxygen bond which under certain reaction conditions, particularly in reducing or basic conditions, is a potential site of ring cleavage. Thus, isoxazoles are very useful intermediates since the ring system stability allows the manipulation of substituents to give functionally complex derivatives, yet it is easily cleaved when necessary. The ring opening provides difunctionalized compounds, namely 1,3-dicarbonyl, enaminoketone, γ-amino alcohol, α,β- unsaturated oxime, β-hydroxy nitrile or β-hydroxy ketone compounds, so that isoxazoles can be considered masked forms of these synthetic units. Consequently, isoxazoles have become an important synthetic tool. The construction of the isoxazole ring can be achieved by several synthetic approaches. However, the two major routes to isoxazoles are the 1,3-dipolar cycloadditon of alkenes and alkynes with nitrile oxides and the reaction of hydroxylamine with a three-carbon atom component, such as 1,3-diketone or an α,β-unsaturated ketone. This review aims to provide coverage of the recent developments on the synthesis and reactivity of isoxazoles.

Objective To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. Methods We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. Results There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] −11.7 to −11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI −13.8 to −12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI −13.7 to −10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2–9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. Conclusions The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.