Synthesis and biological evaluation of (hetero)arylmethyloxy- and arylmethylamine-phenyl derivatives as potent P-glycoprotein modulating agents.

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Colabufo NA, Berardi F, Perrone R, Rapposelli S, Digiacomo M, Vanni M, Balsamo A

Synthesis and biological evaluation of (hetero)arylmethyloxy- and arylmethylamine-phenyl derivatives as potent P-glycoprotein modulating agents.

J Med Chem. 2008 Mar 13;51(5):1415-22. doi: 10.1021/jm701267q. Epub 2008 Feb 8.

PubMed ID
18257545 [ View in PubMed
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Abstract

Starting from lead compounds 12b and 28b, previously characterized as P-glycoprotein (P-gp) modulating agents, two series of new compounds were investigated. Compounds 14a, b and 15a, b displayed high P-gp modulating activity in the submicromolar range (EC 50 values from 0.25 to 0.80 microM). Moreover, amino derivatives 23- 27 showed EC 50 values ranging from 0.085 to 0.90 microM. In the pyridyl series, the best result has been obtained for 4-pyridyl derivative 17b (EC 50 = 0.85 microM). The best P-gp modulating agents 14a, b, 15a, b, and 23- 27 also have been studied for determining their breast cancer resistance protein (BCRP) inhibition activity. The results demonstrated that only the amino derivatives 23- 27 displayed moderate BCRP inhibition activity.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CyclosporineP-glycoprotein 1EC 50 (nM)80000N/AN/ADetails
ElacridarP-glycoprotein 1EC 50 (nM)2000N/AN/ADetails
VerapamilP-glycoprotein 1EC 50 (nM)20000N/AN/ADetails