What does this research mean for the field?

Heteroaryl derivatization of pyridylnaphthalene-type aldosterone synthase inhibitors significantly increases their potency and selectivity for CYP11B2 while reducing unwanted CYP1A2 inhibition, yielding orally bioavailable compounds. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

August 1, 2008Journal of Medicinal ChemistryOpen Access

Overcoming Undesirable CYP1A2 Inhibition of Pyridylnaphthalene-Type Aldosterone Synthase Inhibitors: Influence of Heteroaryl Derivatization on Potency and Selectivity

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Population

In vitro enzyme assays and male Wistar rats

Design

Preclinical

Authors

RHRalf HeimThe University of Queensland SLSimon LucasFachhochschule für Finanzen Brandenburg CGCornelia M. GrombeinHelmholtz Institute for Pharmaceutical Research Saarland

Discussion

Member takes

Implication

These preclinical results are hypothesis-generating; human trials needed before any clinical consideration of CYP11B2 inhibitors.

Structured PICO

Population

In vitro enzyme assays and male Wistar rats

Intervention

Heteroaryl derivatization of pyridylnaphthalene-type aldosterone synthase inhibitors (e.g., methoxyalkyl derivatives 22 and 26, isoquinoline derivatives 28 and 30)

Outcome

CYP11B2 inhibition potency and selectivity against CYP1A2 and CYP11B1surrogate

Heteroaryl derivatization of pyridylnaphthalene-type aldosterone synthase inhibitors yields highly potent and selective compounds with reduced CYP1A2 inhibition and good oral bioavailability in rats.

Cite This Study

Heim et al. (2008) studied this question.

synapsesocial.com/papers/6a1cd23bf1b3da30e489b52b https://doi.org/10.1021/jm800377h

Topics

Heart failure HFrEF treatment

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