Regioselectivity of thiouracil alkylation: Application to optimization of Darapladib synthesis - Université de La Réunion Access content directly
Journal Articles Bioorganic and Medicinal Chemistry Letters Year : 2018

Regioselectivity of thiouracil alkylation: Application to optimization of Darapladib synthesis

Abstract

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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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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