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Article Dans Une Revue Bioorganic and Medicinal Chemistry Letters Année : 2018

Regioselectivity of thiouracil alkylation: Application to optimization of Darapladib synthesis

Résumé

Darapladib is one of the most potent Lp-PLA2 (Lipoprotein-associated phospholipase A2) inhibitor with an IC50 of 0.25 nM. We demonstrate that a crucial step of Darapladib synthesis was not correctly described in the literature, leading to the production of wrong regioisomers. Moreover we show that the inhibitory activity is directly linked to the position on N1 since compounds bearing alkylation on different sites have potentially less interaction within the active site of Lp-PLA2
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Dates et versions

hal-04543200 , version 1 (12-04-2024)

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Florian Guibbal, Sébastien Bénard, Jessica Patché, Vincent Meneyrol, Joël Couprie, et al.. Regioselectivity of thiouracil alkylation: Application to optimization of Darapladib synthesis. Bioorganic and Medicinal Chemistry Letters, 2018, 28 (4), pp.787-792. ⟨10.1016/j.bmcl.2017.12.052⟩. ⟨hal-04543200⟩
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