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Issue 7, 2017
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Structure–metabolism-relationships in the microsomal clearance of piperazin-1-ylpyridazines

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Abstract

In this study, we provide insight into the metabolic profile of a series of piperazin-1-ylpyridazines suffering from rapid in vitro intrinsic clearance in a metabolic stability assay using liver microsomes (e.g. compound 1 MLM/HLM t1/2 = 2/3 min). Aided by empirical metabolite identification and computational predictive models, we designed the structural modifications required to improve in vitro intrinsic clearance by more than 50-fold (e.g. compound 29 MLM/HLM t1/2 = 113/105 min).

Graphical abstract: Structure–metabolism-relationships in the microsomal clearance of piperazin-1-ylpyridazines

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Publication details

The article was received on 04 May 2017, accepted on 20 Jun 2017 and first published on 04 Jul 2017


Article type: Research Article
DOI: 10.1039/C7MD00230K
Citation: Med. Chem. Commun., 2017,8, 1553-1560
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    Structure–metabolism-relationships in the microsomal clearance of piperazin-1-ylpyridazines

    S. Llona-Minguez, A. Ghassemian, P. Baranczewski, M. Desroses, T. Koolmeister, P. Artursson, M. Scobie and T. Helleday, Med. Chem. Commun., 2017, 8, 1553
    DOI: 10.1039/C7MD00230K

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