Studies on pyrrolidinones. On the application of copper-catalyzed arylation of methyl pyroglutamate to obtain a new benzo[de]quinoline scaffold

Ghinet, Alina; Oudir, Souhila; Hénichart, Jean‐Pierre; Rigo, Benoı̂t; Pommery, Nicole; Gautret, Philippe

doi:10.1016/j.tet.2009.10.103

Cited by 17 publications

(8 citation statements)

References 47 publications

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“…As shown in Table 1, CuI cooperated with various types of ligands to effectively catalyze the reaction. Because polyhydroxy groups may deactivate the lactam substrate, we used a large amount31b of CuI and the ligand to achieve complete conversion within a relatively short timeframe.…”

Section: Resultsmentioning

confidence: 99%

N‐Arylated‐Lactam‐Type Iminosugars as New Immunosuppressive Agents: Discovery, Optimization, and Biological Evaluation

Zhang

Zhu

et al. 2014

Chemistry An Asian Journal

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We have previously described the discovery of N-alkylated iminosugars that showed immunosuppressive activity both in vitro and in vivo. Herein, we report the synthesis and biological evaluation of N-arylated lactam-type iminosugar derivatives. The synthesis started from simple monosaccharides and featured a Buchwald-Hartwig coupling reaction to construct the key N-aryl connection, thereby providing a highly diverse compound library. Structure-activity relationship studies, guided by a mouse-spleen-proliferation assay, led to the identification of 'hit' compound 12 f. Subsequently, the systematic modification of compound 12 f afforded compounds 21 h, 21 k, 21 n, 21 t, and 21 x with improved activities (IC50 =12-30 μM) and low Jurkat cytotoxicities (IC50 >100 μM). These new compounds also inhibited the secretion of IFN-γ and IL-4, which are hallmark cytokines of Th1 and Th2 cells, respectively. This work demonstrated that the N-arylated iminosugar structure represents a new scaffold with immunosuppressive activity.

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Section: Resultsmentioning

confidence: 99%

N‐Arylated‐Lactam‐Type Iminosugars as New Immunosuppressive Agents: Discovery, Optimization, and Biological Evaluation

Zhang

Zhu

et al. 2014

Chemistry An Asian Journal

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“…Although many methods, employing catalytic quantities of either copper (38)(39)(40) or palladium (41), have been described, these are often limited to substrates with little steric occlusion of the amide nitrogen. Use of these conditions with our substrate resulted in little or no observed product.…”

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confidence: 99%

Ammonia synthons for the multicomponent assembly of complex γ-lactams

Tan

Martin

Fettinger

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The synthesis of γ-lactams that are unsubstituted at the 1-position (nitrogen) as well as their subsequent N -functionalization is reported. A recently discovered four-component reaction (4CR) is employed with either an ammonia precursor or a protected form of ammonia that can be deprotected in a subsequent synthetic step. These methods represent the first multicomponent assembly of complex lactam structures that are unsubstituted at nitrogen. In addition, two methods for the introduction of nitrogen substituents that are not possible through the original 4CR are reported. X-ray crystallographic analysis of representative structures reveals conformational changes in the core structure that will enable future deployment of this chemistry in the design and synthesis of diverse collections of lactams suitable for the discovery of new biological probes.

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“…To justify the importance of the isoxazole ring on the activity against FTase, we have considered the replacement with a pyrrolidin‐2‐one then with a pyrrolidin‐2‐thione unit. Syntheses started from methyl pyroglutamate 9 which was first N ‐arylated according to a described procedure providing methyl esters 10 and 11 in good yields (Scheme ). Esters were further saponified, and the resulting carboxylic acids 12 and 13 were first activated with thionyl chloride in refluxing dichloromethane, then reacted with zinc dimethyl imidodicarbonimidate in the presence of pyridine and 4 Å powdered molecular sieves affording new pyrrolidinone‐triazines 4a and 4b , by adapting a reported procedure .…”

Section: Resultsmentioning

confidence: 99%

“…To justify the importance of the isoxazole ring on the activity against FTase, we have considered the replacement with a pyrrolidin-2-one then with a pyrrolidin-2-thione unit. Syntheses started from methyl pyroglutamate 9 which was first N-arylated according to a described procedure [32] providing methyl esters 10 and 11 in good Thiolactams 14a,b were thus obtained in very good yields of 91% and 89% respectively.…”

Section: Chemistrymentioning

confidence: 99%

Exploring isoxazoles and pyrrolidinones decorated with the 4,6‐dimethoxy‐1,3,5‐triazine unit as human farnesyltransferase inhibitors

Lucescu

Ghinet

Shova³

et al. 2019

Archiv der Pharmazie

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Unprecedented triazinyl‐isoxazoles were afforded via an effective cycloaddition reaction between nitrile oxides and the scarcely described 2‐ethynyl‐4,6‐dimethoxy‐1,3,5‐triazine as dipolarophile. The biological evaluation of the newly synthesized compounds showed that the inhibition of human farnesyltransferase by zinc complexation could be improved with triazine‐isoxazole moieties. The replacement of the isoxazole unit by a pyrrolidin‐2‐one was detrimental to the inhibitory activity while the pyrrolidin‐2‐thione derivatives conserved the biological potential. The potential of selected compounds to disrupt protein farnesylation in Chinese hamster ovary (CHO) cells transfected with pEGFP‐CAAX was also evaluated.

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Studies on pyrrolidinones. On the application of copper-catalyzed arylation of methyl pyroglutamate to obtain a new benzo[de]quinoline scaffold

Cited by 17 publications

References 47 publications

N‐Arylated‐Lactam‐Type Iminosugars as New Immunosuppressive Agents: Discovery, Optimization, and Biological Evaluation

N‐Arylated‐Lactam‐Type Iminosugars as New Immunosuppressive Agents: Discovery, Optimization, and Biological Evaluation

Ammonia synthons for the multicomponent assembly of complex γ-lactams

Exploring isoxazoles and pyrrolidinones decorated with the 4,6‐dimethoxy‐1,3,5‐triazine unit as human farnesyltransferase inhibitors

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