Aim: To set up a chromatographic strategy for the determination of log P for beyond Rule of 5 (bRo5) drugs. Materials & methods: Capacity factors measured by reverse phase-HPLC. Balance of intermolecular interactions governing systems assessed by partial least squares regression (PLSR) coupled with block relevance anaysis (PLSR-BR) and multiblock PLSR (MBPLSR). Determination of virtual log P obtained through conformationalsampling.Results:logk60ishighlycorrelatedwithlogPforadatasetof36Ro5compliant compounds (R2 = 0.93, Q2 = 0.90). We refer to the value generated via this method as BRlogP. The balance of intermolecular forces controlling BRlogP and log P are very similar. The ElogPs measured for the bRo5 dataset are significantly higher than corresponding BRlogP. Conclusion: The combination of BRlogP and ElogP provides an experimental lipophilicity range for bRo5 compounds.

Experimental lipophilicity for beyond Rule of 5 compounds

Ermondi, Giuseppe
First
;
Vallaro, Maura;Caron, Giulia
Last
2019-01-01

Abstract

Aim: To set up a chromatographic strategy for the determination of log P for beyond Rule of 5 (bRo5) drugs. Materials & methods: Capacity factors measured by reverse phase-HPLC. Balance of intermolecular interactions governing systems assessed by partial least squares regression (PLSR) coupled with block relevance anaysis (PLSR-BR) and multiblock PLSR (MBPLSR). Determination of virtual log P obtained through conformationalsampling.Results:logk60ishighlycorrelatedwithlogPforadatasetof36Ro5compliant compounds (R2 = 0.93, Q2 = 0.90). We refer to the value generated via this method as BRlogP. The balance of intermolecular forces controlling BRlogP and log P are very similar. The ElogPs measured for the bRo5 dataset are significantly higher than corresponding BRlogP. Conclusion: The combination of BRlogP and ElogP provides an experimental lipophilicity range for bRo5 compounds.
2019
1
1
FDD10
FDD10
BRlogP, bRo5, lipophilicity
Ermondi, Giuseppe; Vallaro, Maura; Goetz, Gilles; Shalaeva, Marina; Caron, Giulia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1725129
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