Search results for "γ-lactams"

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Anticancer potential of novel α,β-unsaturated γ-lactam derivatives targeting the PI3K/AKT signaling pathway.

2021

Abstract Six recently synthesized alkyl (Z)-2-(2-oxopyrrolidin-3-ylidene)acetates were evaluated for their potential as cytotoxic and anticancer agents. All compounds were tested in the ERα positive MCF-7, triple negative MDA-MB-231, and Her2+ SKBR-3 breast cancer cell lines. The most lipophilic derivatives, bearing the 4-isopropylphenyl (2) or 4-tert-butylphenyl (3) group at the γ-lactam nitrogen, proved to be cytotoxic against all the cancer cell lines tested (IC50 values ranging from 18 to 63 μM), exerting their greatest activity in SKBR-3 cells, with IC50 values of 33 and 18 μM, respectively. Biological studies showed that the cytotoxic effects of 2 and 3 are accompanied by apoptotic de…

0301 basic medicineLactamsCell SurvivalAntineoplastic AgentsApoptosisBreast NeoplasmsBiochemistry03 medical and health scienceschemistry.chemical_compoundPI3K/AKT signaling pathwayPhosphatidylinositol 3-Kinases0302 clinical medicinebreast cancerCytotoxic T cellHumansα-methylene-γ-lactamsαβ-unsaturated lactamsCytotoxicityPI3K/AKT/mTOR pathwayPhosphoinositide-3 Kinase InhibitorsPharmacologychemistry.chemical_classificationBiological ProductsMolecular StructureChemistryCell growthAkt/PKB signaling pathwayCell CycleEpithelial Cells030104 developmental biologyEnzymeGene Expression RegulationApoptosis030220 oncology & carcinogenesisCancer researchLactamcytotoxicityFemaleProto-Oncogene Proteins c-aktBiochemical pharmacology
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Desymmetrization of Prochiral Cyclobutanones via Nitrogen Insertion: A Concise Route to Chiral γ‐Lactams

2021

Abstract Asymmetric access to γ‐lactams is achieved via a cyclobutanone ring expansion using widely available (1S,2R)‐1‐amino‐2‐indanol for chiral induction. Mechanistic analysis of the key N,O‐ketal rearrangement reveals a Curtin–Hammett scenario, which enables a downstream stereoinduction (up to 88:12 dr) and is corroborated by spectroscopic, crystallographic, and computational studies. In combination with an easy deprotection protocol, this operationally simple sequence allows the synthesis of a range of optically pure γ‐lactams, including those bearing all‐carbon quaternary stereocenters. In addition, the formal synthesis of drug molecules baclofen, brivaracetam, and pregabalin further …

γ-lactamsChiral auxiliary010405 organic chemistryChemistryasymmetric synthesisEnantioselective synthesisCyclobutanoneGeneral Chemistry010402 general chemistryRing (chemistry)01 natural sciencesCombinatorial chemistryDesymmetrizationCatalysis0104 chemical sciencesStereocenterdesymmetrizationFormal synthesischemistry.chemical_compoundMoleculecyclobutanoneResearch ArticlesResearch ArticleAsymmetric Synthesis | Hot PaperAngewandte Chemie International Edition
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