RESUMEN
The synthesis of a biologically relevant 2-amino-N3-alkylamido 4-quinazolinone has been accomplished in four steps from commercially available materials using design principles from both modular and divergent synthesis. N3-Alkylation of 2-chloro-4(3H)-quinazolinone using methyl bromoacetate, followed by C2-amination produced a suitable scaffold for introducing molecular diversity. Optimization of alkylation conditions afforded full regioselectivity, enabling exclusive access to the N-alkylated isomer. Subsequent C2-amination using piperidine, pyrrolidine, or diethylamine, followed by amide bond formation using variously substituted phenethylamines, generated fifteen unique 4-quinazolinones bearing C2-amino and N3-alkylamido substituents. These efforts highlight the reciprocal influence of C2 and N3 substitution on functionalization at either position, establish an effective synthetic pathway toward 2,N3-disubstituted 4-quinazolinones, and enable preliminary bioactivity studies while providing an experiential learning opportunity for undergraduate student researchers.
RESUMEN
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor associated with high mortality if metastases are identified. Currently, there is no standardized nor curative treatment for neurometastatic MCC. In this study, we have reviewed the more recent cases and the use of immunotherapy in a population. In this case report and review, we present a case of MCC with brain metastasis currently undergoing treatment with immunotherapy (pembrolizumab) resulting in an initial complete response with a progression-free survival time of five months. We also review the past reported literature and the 11 newly presented cases on their clinical presentation of neurometastatic MCC, immunohistochemical markers, and treatment outcomes. In summary, immunotherapy initially showed a promising response with the complete elimination of MCC brain metastasis. The early aggressive treatment of pembrolizumab with stereotactic radiosurgery should be considered as this treatment plan has shown improved therapeutic effects compared to the standard chemoradiation therapy. Further investigations are needed to determine the efficacy and response of immunotherapy use for neurometastatic MCC.
