New efficient access to fused (Het)Aryltetrahydroindolizinones via N-acyl iminium intermediates

Chiurato, Matteo; Boulahjar, Rajâa; Routier, Sylvain; Troin, Yves; Guillaumet, Gérald

doi:10.1016/j.tet.2010.03.100

Cited by 25 publications

(12 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some of them have entered clinical trials. More recently, we reported an original synthesis leading to het(aryl)indolizinones A via an (acyl)iminium intermediate (Figure ) . Thus, we envisioned the use of our optimized synthetic pathway leading to tetrahydropyrido[1,2- a ]isoindolone B as the central core for new CDK inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Novel Tetrahydropyrido[1,2-a]isoindolone Derivatives (Valmerins): Potent Cyclin-Dependent Kinase/Glycogen Synthase Kinase 3 Inhibitors with Antiproliferative Activities and Antitumor Effects in Human Tumor Xenografts

et al. 2012

Self Cite

View full text Add to dashboard Cite

The development of CDK and GSK3 inhibitors has been regarded as a potential therapeutic approach, and a substantial number of diverse structures have been reported to inhibit CDKs and GSK-3β in recent years. Only a few molecules have gone through or are currently undergoing clinical trials as CDK and GSK inhibitors. In this paper, we prepared valmerins, a new family containing the tetrahydropyrido[1,2-a]isoindone core. The fused heterocycle was prepared with a straightforward synthesis that was functionalized by a (het)arylurea. Twelve valmerins inhibited the CDK5 and GSK3 with an IC(50) < 100 nM. A semiquantitative kinase scoring was realized, and a cellular screening was done. At the end of our study, we investigated the in vivo potency of one valmerin. Mice exhibited good tolerance to our lead, which proved its efficacy and clearly blocked tumor growth. Valmerins appear also as good candidates for further development as anticancer agents.

show abstract

Section: Introductionmentioning

confidence: 99%

Novel Tetrahydropyrido[1,2-a]isoindolone Derivatives (Valmerins): Potent Cyclin-Dependent Kinase/Glycogen Synthase Kinase 3 Inhibitors with Antiproliferative Activities and Antitumor Effects in Human Tumor Xenografts

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…In particular, these are skeletons that have been found as a DPP4 inhibitor, PNKP inhibitor, and porcupine inhibitor . Until now, the multicomponent reaction, Lewis acid or metal-catalyzed cascade reaction, [3 + 2] cycloaddition reaction, and traditional multistep synthesis have been reported to synthesize this framework. However, the asymmetric synthesis of pyrrolo[3,4- b ]pyridines mainly focused on the substrate-induction and chiral-resolution method .…”

mentioning

confidence: 99%

N-Heterocyclic Carbene-Catalyzed Atroposelective Synthesis of Pyrrolo[3,4-b]pyridines with Configurationally Stable C–N Axial Chirality

Chu

et al. 2022

Org. Lett.

View full text Add to dashboard Cite

The first atroposelective synthesis of pyrrolo[3,4-b]pyridines catalyzed by N-heterocyclic carbene has been achieved. A wide range of chiral atropisomers of pyrrolo[3,4-b]pyridines were obtained in high yields with excellent enantioselectivities (96–99% enantiomeric excess). The experimental results and density functional theory calculations showed that the C–N axial chirality of the product had high thermal stability.

show abstract

“…Nevertheless, appreciable absorption extinction of >2000 cm −1 M −1 was observed for all I−IV at 355 nm of the third harmonic Nd:YAG laser, the most popular commercial excitation source for MALDI. 29,30 Among the title compounds, COOH-NHMe (IV) exhibits the highest extinction coefficient at 355 nm. It is also worth noting that the formation of intramolecular H-bond is critical to enhance the charge transfer character and hence the red shift of the absorption.…”

mentioning

confidence: 99%

“…Based on these criteria and the dual acid–base functionality, we strategically designed and synthesized a series of new MALDI matrices I – IV (see Scheme ) containing a simple aniline derivative anchored by a carboxyl group for COOH-NH 2 ( I ) and COOH-NHMe ( IV ), and formyl group for CHO-NH 2 ( II) , and CHO-NHAc (III) . Though I – IV have been synthesized previously, their related application as a MALDI matrix as part of a rationally designed strategy have not been proposed, especially for II – IV . − The amphoteric property of COOH-NH 2 ( I ) and COOH-NHMe ( IV ) could allow the detection of both positive and negative ions in MALDI. In this study, we demonstrated that these dual polarity MALDI matrix, COOH-NH 2 ( I ) and COOH-NHMe ( IV ), allowed complementary analysis of lipids and proteins, including the positively charged and negatively charged species, within one experiment.…”

mentioning

confidence: 99%

Toward the Rational Design of Universal Dual Polarity Matrix for MALDI Mass Spectrometry

Huang

Lin

et al. 2020

Anal. Chem.

View full text Add to dashboard Cite

A series of novel anthranilic acid derivatives I–IV, of which COOH-NH2 (I) and COOH-NHMe (IV) are endowed with acid and base bifunctionality, were designed and synthesized for matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry applications in dual polarity molecular imaging of biological samples, particularly for lipids. The heat of protonation, deprotonation, and proton transfer reaction as well as the capability of analyzing biomolecules in both positive and negative ion modes for I–IV were systematically investigated under standard 355 nm laser excitation. The results indicate correlation between dual polarity and acid–base property. Further, COOH-NHMe (IV) showed a unique performance and was successfully applied as the matrix for MALDI-TOF mass spectrometry imaging (MSI) for studying the mouse brain. Our results demonstrate the superiority of COOH-NHMe (IV) in detecting more lipid and protein species compared to commercially available matrices. Moreover, MALDI-TOF MSI results were obtained for lipid distributions, making COOH-NHMe (IV) a potential next generation universal matrix.

show abstract

New efficient access to fused (Het)Aryltetrahydroindolizinones via N-acyl iminium intermediates

Cited by 25 publications

References 34 publications

Novel Tetrahydropyrido[1,2-a]isoindolone Derivatives (Valmerins): Potent Cyclin-Dependent Kinase/Glycogen Synthase Kinase 3 Inhibitors with Antiproliferative Activities and Antitumor Effects in Human Tumor Xenografts

Novel Tetrahydropyrido[1,2-a]isoindolone Derivatives (Valmerins): Potent Cyclin-Dependent Kinase/Glycogen Synthase Kinase 3 Inhibitors with Antiproliferative Activities and Antitumor Effects in Human Tumor Xenografts

N-Heterocyclic Carbene-Catalyzed Atroposelective Synthesis of Pyrrolo[3,4-b]pyridines with Configurationally Stable C–N Axial Chirality

Toward the Rational Design of Universal Dual Polarity Matrix for MALDI Mass Spectrometry

Contact Info

Product

Resources

About