Crystal structures and phase relationships of 2 polymorphs of 1,4-Diazabicyclo[3.2.2]nonane-4-Carboxylic Acid 4-Bromophenyl Ester Fumarate, A selective a-7 nicotinic receptor partial agonist

Two polymorphs of the 1:1 fumarate salt of 1,4-diazabicyclo[3.2.2]nonane-4-carboxylic acid 4-bromophenyl ester, developed for the treatment of cognitive symptoms of schizophrenia and Alzheimer disease, have been characterized. The 2 crystal structures have been solved, and their phase relationships...

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Detalles Bibliográficos
Autores: Robert, Benoit, Perrin, Marc-Antoine, Barrio Casado, María del|||0000-0003-3467-7581, Tamarit Mur, José Luis|||0000-0002-7965-0000, Coquerel, Gerard, Céolin, René, Rietveld, Ivo B.
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/103613
Acceso en línea:https://hdl.handle.net/2117/103613
https://dx.doi.org/10.1016/j.xphs.2015.10.015
Access Level:acceso abierto
Palabra clave:Crystals
Thermodynamics
polymorphism
thermodynamics
physical stability
solid state
phase transition
topological phase diagram
Clapeyron equation
crystal structure
high pressure
thermal analysis
Termodinàmica
Cristalls
Àrees temàtiques de la UPC::Física::Física de l'estat sòlid
Descripción
Sumario:Two polymorphs of the 1:1 fumarate salt of 1,4-diazabicyclo[3.2.2]nonane-4-carboxylic acid 4-bromophenyl ester, developed for the treatment of cognitive symptoms of schizophrenia and Alzheimer disease, have been characterized. The 2 crystal structures have been solved, and their phase relationships have been established. The space group of form I is P21/c with a unit-cell volume of 1811.6 (5) Å3 with Z = 4. The crystals of form I were 2-component nonmerohedral twins. The space group of form II is P21/n with a unit-cell volume of 1818.6 (3) Å3 with Z = 4. Relative stabilities have been inferred from experimental and topological P-T diagrams exhibiting an overall enantiotropic relationship between forms I and II although the solid–solid transition has never been observed. The slope of the I-II equilibrium in the P-T diagram is negative, form II is the stable phase below the solid–solid transition temperature of 371 K, and form I exhibits a stable melting equilibrium. The I-II transition temperature has been obtained from the intersection of the sublimation curves of the 2 solid forms.