Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2487911 | Journal of Pharmaceutical Sciences | 2006 | 16 Pages |
Abstract
The physicochemical and biopharmaceutical properties, such as pKa, crystal habit, water solubility, logD, molecular structure and dynamics, and membrane permeability of CR3124 (endo-2-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-1H-benz[e]isoindol-1-one, a novel potent 5-HT3 receptor antagonist) have been studied in order to obtain preformulation information. The study showed that CR3124 is a very rigid molecule in which conformational freedom due to the presence of a rotatable bond is restricted by the interaction between an activated hydrogen and the amide oxygen and the conformation of the tropane piperidine ring is regulated by the environment in such a manner as to optimize the intermolecular interactions with the solvent. This chameleon behavior appears to be capable of explaining the biopharmaceutical properties showed by CR3124, such as low wettability, relatively good solubility, and very high membrane permeability.
Keywords
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Andrea Cappelli, Valter Travagli, Iacopo Zanardi, Maurizio Anzini, Gianluca Giorgi, Alessandro Donati, Marianna Aggravi, Mario Casolaro, Massimo Fresta, Eugenio Paccagnini, Francesco Makovec, Salvatore Vomero,