Oxazoles, Benzoxazoles, and Isoxazoles

The C2 proton of oxazole is mildly acidic with a theoretical pKa value of n The C2 benzoxazole proton is slightly more acidic than oxazole 

Oxazoles are known in natural products and also find wide incorporation into synthetic medicinal compounds. Oxazoles can be found in the natural products (-)-hennoxazole A (antiviral) and leucascandrolide A (cytotoxic and antifungal). Benzoxazoles and isoxazoles are less common in natural products. Pseudo-pteroxazole (benzoxazole-containing anti-tubercular agent) and ibotenic acid (isoxazole-containing neurotoxin) are two examples. 

Oxazoles and benzoxazoles with an aryl substituent at C2 are strongly fluorescent and can act as an optical brightener. Some washing agents include 4,4 -bis(benzoxazol-2-yl)stilbene as an additive. The additive is 

Tilmacoxib is a COX-2 inhibiting, oxazole-containing, nonsteroidal anti-inflammatory agent, and valdecoxib is an isoxazole NSAID. Formation of the sodium salt of an A -acylated derivative of valdecoxib affords parecoxib, a water-soluble valdecoxib prodrug amenable to injectable formulations. Valdecoxib was withdrawn from the US market in 2005 due to concern of increased risk of heart attack or stroke. While parecoxib is approved for use in the EU, the US FDA issued a letter of nonapproval for the drug, also in 2005. While no documentation for the nonapproval was made public, proximity to the 2004 withdrawal of rofecoxib (Vioxx) cannot be overlooked. 

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