2,6-Quinolinyl derivatives as potent VLA-4 antagonists

Lassoie, Marie‐Agnes; Broeders, Fabienne; Collart, Philippe; Defrère, Laurent; Laveleye-Defais, Françoise de; Demaude, Thierry; Gassama, Abdoulaye; Guillaumet, Gérald; Hayez, Jean-Claude; Kiss, László; Knerr, Laurent; Nicolas, Jean‐Marie; Norsikian, Stéphanie; Quéré, Luc; Routier, Sylvain; Verbois, Valérie; Provins, Laurent

doi:10.1016/j.bmcl.2006.09.069

Cited by 10 publications

(3 citation statements)

References 41 publications

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“…25 Compounds 12c and 12e were treated with acetyl chloride 26 to obtain their acetyl derivatives 12c′ and 12e′ , respectively (Scheme 5 ). Reduction of the nitro group 27 28 29 in 12m with H 2 and Pd/C or SnCl 2 was possible, but the obtained product was too unstable to be isolated by column chromatography. Additional efforts to react 12m by reduction and acylation to produce an amide derivative in a one-pot procedure were investigated.…”

Section: Table 1 Ic 50 Valu...mentioning

confidence: 99%

Synthesis and Cytotoxic Evaluation of 2-Aryl-7,8-dihydroquinolin-6(5H)-ones

Blé González,

Martínez,

Bautista

et al. 2023

Synthesis

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Herein we present a facile four-step synthetic method for the synthesis of novel 2-aryl-substituted 7,8-dihydroquinolin-6(5H)-ones as cytotoxic agents. The key step was the use of Mannich salts derived from acetophenones as a Michael acceptor in the reaction with cyclohexane-1,4-dione monoethylene acetal to give 1,5-dicarbonyl compounds that were treated with ammonium acetate to give the 7,8-dihydroquinolin-6(5H)-ones. The cytotoxic activity of the synthesized compounds was evaluated against seven cell lines. The observed data showed good selectivity for chronic myeloid leukemia line K-562. The synthetic route was simple and applicable to various functional group containing substrates. These types of compounds may be utilized as lead compounds in cancer research and drug discovery.

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Section: Table 1 Ic 50 Valu...mentioning

confidence: 99%

Synthesis and Cytotoxic Evaluation of 2-Aryl-7,8-dihydroquinolin-6(5H)-ones

Blé González,

Martínez,

Bautista

et al. 2023

Synthesis

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“…Finally, Elan has described a series of azabenzimidazolinones such as compound 64 incorporating various acyl groups selected from their own and the work of other researchers in the field in a patent application [152] . Figure 10 includes a number of structures, including the quinoline 65 [153] , bearing interesting features that are not typically associated with potent α 4 integrin antagonists. The piperazine 66 is only moderately potent in a Jurkat cell/VCAM binding assay (IC 50 : 1122 ± 250 nM), but has excellent bioavailability (F = 86%) and lower biliary clearance than many of the other analogs in the same series.…”

Section: Small Molecule Derived From N -Acylphenylalaninesmentioning

confidence: 99%

Very late antigen-4 integrin antagonists

Tilley

2008

Expert Opinion on Therapeutic Patents

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“…The development of small-molecule VLA-4 antagonists represents a promising approach to treat this class of inflammatory diseases. As a part of these efforts, UCB-108770 ( 1 ) (Figure ) was identified as a potent VLA-4 antagonist …”

Section: Introductionmentioning

confidence: 99%

Efficient Multikilogram Synthesis of a VLA-4 Antagonist via a Povarov Reaction

Cerfontaine

Driessens

Deltent

et al. 2019

Org. Process Res. Dev.

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Herein we describe the practical synthesis of a novel VLA-4 antagonist 1 as a potential treatment for multiple sclerosis. The key step is based on the Povarov reaction of an imine with an alkene to access a tetrahydroquinoline intermediate, leading to the corresponding quinoline core after an oxidative aromatization step. The development of the synthesis of 1 led to decreased complexity and the elimination of chromatographic purifications. These improvements were demonstrated at scale by the production of 32 kg of 1 in high yield with excellent purity.

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2,6-Quinolinyl derivatives as potent VLA-4 antagonists

Cited by 10 publications

References 41 publications

Synthesis and Cytotoxic Evaluation of 2-Aryl-7,8-dihydroquinolin-6(5H)-ones

Synthesis and Cytotoxic Evaluation of 2-Aryl-7,8-dihydroquinolin-6(5H)-ones

Very late antigen-4 integrin antagonists

Efficient Multikilogram Synthesis of a VLA-4 Antagonist via a Povarov Reaction

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