Structural studies of five novel bile acid-4-aminopyridine conjugates.

Kari V Ahonen, Manu K Lahtinen, Miika S Löfman, Anniina M Kiesilä, Arto M Valkonen, Elina I Sievänen, Nonappa, Erkki T Kolehmainen

Index: Steroids 77(11) , 1141-51, (2012)

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Abstract

Synthesis and solid-state structural characterization of five bile acid amides of 4-aminopyridine (4-AP) are reported. Systematic crystallization experiments revealed a number of structural modifications and/or solvate/hydrate systems for these conjugates. Particularly, cholic acid conjugate exhibited five distinct structure modifications, including one anhydrous form, mono- and dihydrates, as well as ethanol and 2-butanol solvates. The obtained crystal forms were examined extensively with various analytical methods, including solid-state NMR, Raman, and IR spectroscopies, powder and single crystal X-ray diffraction methods, thermogravimetry, and differential scanning calorimetry. After releasing their crystal solvent molecules, the resulted non-solvated structure forms showed 50-75°C higher melting points than corresponding bile acids, and thermal degradation occurred for all conjugates at about 300-330°C. Moreover, the single crystal X-ray structure of the ursodeoxycholic acid-4-aminopyridine conjugate is reported.Copyright © 2012 Elsevier Inc. All rights reserved.