Stereodivergent Desymmetrization of Phenols En Route to Modular Access to Densely Functionalized Quinazoline and Oxazine Scaffolds.

The de novo assembly of stereochemically and skeletally diverse scaffolds is a powerful tool for the discovery of novel chemotypes. Hence, the development of modular, step- and atom-economic synthetic methods to access stereochemically and skeletally diverse compound collection is particularly important. Herein, we show a metal-free, stereodivergent build/couple/pair strategy that allows access to a unique collection of benzo[5,6][1,4]oxazino[4,3-a]quinazoline, quinolino[1,2-a]quinazoline and benzo[b]benzo [4,5]imidazo[1,2-d][1,4]oxazine scaffolds with complete diastereocontrol and wide distribution of molecular architectures. This metal-free process proceeds via desymmetrization of phenol derivatives. The cascade unites Mannich with aza-Michael addition reactions, providing expeditious entries to diverse classes of molecular shapes in a single operation.

Pharmaceutical equivalency of locally and regionally manufactured generic pharmaceutical products in UAE.

Generic drugs or generic medicines are pharmaceutical products manufactured to be equivalent to the brand/innovator drug products. They represent the majority of worldwide prescribed medicines; therefore, their quality is critical to maximize patients' therapeutic outcomes. This study aimed to evaluate the pharmaceutical equivalency of locally and regionally manufactured generic pharmaceutical products being sold in the United Arab Emirates (UAE) market to enhance public confidence, promote their utilization, and reduce treatment costs. Three drugs (tadalafil, rosuvastatin, and acetaminophen) from three different pharmacological classes were selected from the UAE market as representatives for generic drugs. At least two generic products for each locally (L) and regionally (R) manufactured generic were evaluated according to the USP criteria in comparison to the brand (B) comparator product. All comparative tests were performed before storage and 3 and 6 months after storage during the accelerated stability study performed under the conditions for climatic zone IV (40 °C ± 2 °C /75% RH ± 5% RH). Although results were statistically different from the comparators using ANOVA and Tukey's Kremer post hoc tests, all tests were within the USP acceptance limits, except one, for friability, disintegration, content uniformity, and dissolution. Significant changes were observed following their storage over 6 months during accelerated stability studies, however, without failing the USP limits. Only one locally manufactured acetaminophen generic failed the USP dissolution tests before and after its storage and failed the disintegration test following its storage under accelerated conditions for zone IV. In conclusion, the majority of the locally and regionally manufactured generic products being sold in the UAE market were of good quality and performed similarly to their comparators. However, a continuous independent quality evaluation for the marketed generic drugs is essential to enhance public confidence.