Abstract
A library of novel 2-(het)arylpyrrolidine-1-carboxamides were obtained via a modular approach based on the intramolecular cyclization/Mannich-type reaction of N-(4,4-diethoxybutyl)ureas. Their anti-cancer activities both in vitro and in vivo were tested. The in vitro activity of some compounds towards M-Hela tumor cell lines was twice that of the reference drug tamoxifen, whereas cytotoxicity towards normal Chang liver cell did not exceed the tamoxifen toxicity. In vivo studies showed that the number of surviving animals on day 60 of observation was up to 83% and increased life span (ILS) was up to 447%. Additionally, some pyrrolidine-1-carboxamides possessing a benzofuroxan moiety obtained were found to effectively suppress bacterial biofilm growth. Thus, these compounds are promising candidates for further development both as anti-cancer and anti-bacterial agents.
Highlights
The pyrrolidine moiety is an important structural part of many natural alkaloids [1,2,3,4] and one of the most frequently occurring heterocyclic scaffolds in approved drugs [5]
We started our research from the synthesis of initial N-(4,4-diethoxybutyl)ureas 1 by the previously
We started our research from the synthesis initial
Summary
The pyrrolidine moiety is an important structural part of many natural alkaloids [1,2,3,4] and one of the most frequently occurring heterocyclic scaffolds in approved drugs [5]. A number of anti-cancer drugs possess an N-carboxypyrrolidine scaffold. These include both fairly old ones (e.g., dactinomycin [6], approved in 1964) and those that have appeared recently. Acalabrutinib [7,8]. Larotrectinib is the first drug to be developed and approved to treat any cancer containing certain mutations, as opposed to cancers of specific tissues. It should be emphasized that both acalabrutinib and larotrectinib contain a 2-(het)aryl-substituted
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