Determination of aqueous stability and degradation products of series of coumarin dimers.

Authors :: Dragojević S
Sunjić V
Bencetić-Mihaljević V
Ralić J
Mesić M
Elenkov IJ
Sucić AF
Klonkay AC
Lerman L
Ilijas M
Gabelica-Marković V
Malnar I
Source :: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2011 Jan 05; Vol. 54 (1), pp. 37-47. Date of Electronic Publication: 2010 Aug 13.
Publication Year :: 2011
Abstract: The stability in aqueous solution of five classes of coumarin dimers (I-V, compounds 1-29) was studied by HPLC-MS/MS at various pH values. The relationship between chemical structure and stability is discussed. It was found that dimeric compounds with strong electron withdrawing groups (EWGs) on the α-carbon to the bridging C-atom are stable at all pH values, whereas other derivatives undergo retro-Michael addition at rates which are also affected by the substituents on the aromatic rings. In some cases formation of stable isomers or oxidation products was observed. In order to evaluate their developability and potential for progression to in vivo studies, representative compounds were tested in an in vitro microsomal stability assay.<br /> (Copyright © 2010 Elsevier B.V. All rights reserved.)

Subjects :: Animals
Carbon chemistry
Chromatography, High Pressure Liquid methods
Hydrogen-Ion Concentration
Kinetics
Male
Mass Spectrometry methods
Mice
Microsomes, Liver drug effects
Models, Chemical
Oxygen chemistry
Solvents chemistry
Chemistry, Pharmaceutical methods
Coumarins chemistry
Water chemistry

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