title: 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 α-7 Nicotinic Receptor Partial Agonist.
abstract: 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) Å(3) 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) Å(3) 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.
authors: Normandie University, SMS EA3233, University of Rouen, rue Lucien Tesnière, 76821, Mont Saint Aignan Cedex, France; Sanofi R&D, Lead Generation and Compound Realization/Analytical Sciences/Solid State group, F-94400 Vitry sur Seine, France.
authors: Benoît
authors: B
authors: Robert
authors: Sanofi R&D, Lead Generation and Compound Realization/Analytical Sciences/Solid State group, F-94400 Vitry sur Seine, France.
authors: Marc-Antoine
authors: MA
authors: Perrin
authors: Grup de Caracterització de Materials (GCM), Departament de Física i Enginyeria Nuclear, Universitat Politècnica de Catalunya, ETSEIB, 08028 Barcelona, Spain.
authors: Maria
authors: M
authors: Barrio
authors: Grup de Caracterització de Materials (GCM), Departament de Física i Enginyeria Nuclear, Universitat Politècnica de Catalunya, ETSEIB, 08028 Barcelona, Spain.
authors: Josep-Lluis
authors: JL
authors: Tamarit
authors: Normandie University, SMS EA3233, University of Rouen, rue Lucien Tesnière, 76821, Mont Saint Aignan Cedex, France.
authors: Gérard
authors: G
authors: Coquerel
authors: Caractérisation des Matériaux à Activité Thérapeutique (CAMMAT), Faculté de Pharmacie de l'Université Paris Descartes, F-75006 Paris, France.
authors: René
authors: R
authors: Ceolin
authors: Caractérisation des Matériaux à Activité Thérapeutique (CAMMAT), Faculté de Pharmacie de l'Université Paris Descartes, F-75006 Paris, France. Electronic address: ivo.rietveld@parisdescartes.fr.
authors: Ivo B
authors: IB
authors: Rietveld
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry* / Q000494:pharmacology; D003460:Crystallization; D054333:Drug Partial Agonism; D005650:Fumarates / Q000737:chemistry; D008956:Models, Chemical; D018722:Nicotinic Agonists / Q000737:chemistry* / Q000494:pharmacology; D044367:Phase Transition; D013818:Thermogravimetry; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D005650:Fumarates; D018722:Nicotinic Agonists; C516833:SSR180711; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: Clapeyron equation; crystal structure; high pressure; phase transition; physical stability; polymorphism; solid state; thermal analysis; thermodynamics; topological phase diagram