Drug Res (Stuttg) 2018; 68(09): 514-520
DOI: 10.1055/s-0044-102096
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

In Vitro Studies on Physiological and Chemical Stability of New LE404-Derivatives with Extended Half-Life

Stephanie Zergiebel
1   Institute of Pharmacy, Friedrich-Schiller University Jena, Jena, Germany
,
Andreas Seeling
1   Institute of Pharmacy, Friedrich-Schiller University Jena, Jena, Germany
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 04. Januar 2018

accepted 31. Januar 2018

Publikationsdatum:
06. März 2018 (online)

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Abstract

Dibenzoazecines are a class of potential neuroleptics with high affinity to dopamine and serotonin receptors. The efficacy and high therapeutic range has already been demonstrated in vivo with the lead structure 7-methyl-5,6,7,8,9,14-hexahydrodibenzo[d,g]azecin-3-ol (LE404) and selected derivatives. There is a variety of new synthesized structurally different dibenzoazecine derivatives with the aim to improve pharmacokinetic parameters, all of which contain the lead structure LE404. For a multitude of these substances is still a lack of information, inclusive of stability, physicochemical parameters, pharmacokinetics and metabolism. Therefore, the present study investigated the stability properties of 17 new azecine derivatives, including esterase cleavage, stability in simulated gastrointestinal fluid, stability at different pH-values and determination of octanol/water-partition coefficients. These findings, in correlation to the properties and efficacy of the already in vivo tested substances, will be useful for safety and efficacy in further in vivo tests.