Recently, we reported the use of a sequence of alkylation and dehydration methodologies to obtain new non‐proteinogenic amino acids (N‐ethyl α,β‐dehydroamino acids) from the methyl esters of N‐(4‐nitrophenylsulfonyl) β‐hydroxy amino acids. Thus, it was possible to obtain for the first time, non‐natural amino acids that incorporate both N‐ethyl and α,β‐dehydro moieties. Herein, we report the application of this N‐alkylation procedure to several methyl esters of β,β‐dibromo and β‐bromo β‐substituted dehydroamino acids protected with standard amine protecting groups such as tert‐butyloxycarbonyl, benzyloxycarbonyl, and (4‐nitrobenzyl)oxycarbonyl, as well as acyl and sulfonyl groups. The procedure allows the synthesis of the methyl esters of N‐protected N‐ethyl β,β‐dibromo and N‐ethyl β‐bromo β‐substituted dehydroamino acids in fair to high yields. Some of these N‐ethylated dehydroamino acid derivatives were used as substrates in cross‐coupling reactions to give β,β‐disubstituted N‐ethyldehydroalanine derivatives.
An in silico study focused on known cancer-related target proteins, identified a selection of imidazo [4,5-b]pyrrolo [3,4d]pyridines as potentially active. These compounds were prepared by a novel synthetic approach, designed and developed in-house, based on the reaction of 5-amino-4cyanoformimidoyl imidazoles with N-substituted cyanoacetamides. The substituted imidazolylpyrrolones obtained, were cyclized intramolecularly to generate the intended imidazo[4,5b]pyrrolo [3,4-d]pyridines in a process catalyzed by DBU. Treat-ing the imidazolylpyrrolones with an excess of triethyl orthoformate and heating at 80 °C in the presence of acid catalysis led to imidazopyrrolodiazepines. These compounds were screened for their anticancer potential, using the renal cell carcinoma cell line model (A498 and 786-O cell lines). Two compounds exhibited IC 50 values in the low micromolar range with a good selectivity index, when compared to non-neoplastic kidney cell line HK2 and the reference compounds rapamycin, cediranib and sunitinib.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.