title: Crystal structures of five new substituted tetrahydro-1-benzazepines with potential antiparasitic activity.
abstract: Tetrahydro-1-benzazepines have been described as potential antiparasitic drugs for the treatment of chagas disease and leishmaniasis, two of the most important so-called `forgotten tropical diseases' affecting South and Central America, caused by Trypanosoma cruzi and Leishmania chagasi parasites, respectively. Continuing our extensive work describing the structural characteristics of some related compounds with interesting biological properties, the crystallographic features of three epoxy-1-benzazepines, namely (2SR,4RS)-6,8-dimethyl-2-(naphthalen-1-yl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, (1), (2SR,4RS)-6,9-dimethyl-2-(naphthalen-1-yl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, (2), and (2SR,4RS)-8,9-dimethyl-2-(naphthalen-1-yl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, (3), all C22H21NO, and two 1-benzazepin-4-ols, namely 7-fluoro-cis-2-[(E)-styryl]-2,3,4,5-tetrahydro-1H-1-benzazepin-4-ol, C18H18FNO, (4), and 7-fluoro-cis-2-[(E)-pent-1-enyl]-2,3,4,5-tetrahydro-1H-1-benzazepin-4-ol, C15H20FNO, (5), are described. Some peculiarities in the crystallization behaviour were found, involving significant variations in the crystalline structures as a result of modest changes in the peripheral substituents in (1)-(3) and the occurrence of discrete disorder due to the molecular overlay of enantiomers with more than one conformation in (5). In particular, an interesting phase change on cooling was observed for compound (5), accompanied by an approximate fourfold increase of the unit-cell volume and a change of the Z' value from 1 to 4. This transition is a consequence of the partial ordering of the pentenyl chains in half of the molecules breaking half of the -3 symmetry axes observed in the room-temperature structure of (5). The structural assembly in all the title compounds is characterized by not only (N,O)-H...(O,N) hydrogen bonds, but also by unconventional C-H...O contacts, resulting in a wide diversity of packing.
authors.affiliation: Grupo INTERFASE, Universidad Industrial de Santander, Ciudad Universitaria, Bucaramanga, Colombia.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Macías
authors.affiliation: Laboratorio de Síntesis Orgánica, Escuela de Química, Universidad Industrial de Santander, AA 678 Bucaramanga, Colombia.
authors.forename: Lina M
authors.initials: LM
authors.lastname: Acosta
authors.affiliation: Laboratorio de Síntesis Orgánica, Escuela de Química, Universidad Industrial de Santander, AA 678 Bucaramanga, Colombia.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Sanabria
authors.affiliation: Laboratorio de Síntesis Orgánica, Escuela de Química, Universidad Industrial de Santander, AA 678 Bucaramanga, Colombia.
authors.forename: Alirio
authors.initials: A
authors.lastname: Palma
authors.affiliation: Université de Lille, CNRS UMR 8181, Unité de Catalyse et Chimie du Solide (UCCS), ENSCL, F-59000 Lille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Roussel
authors.affiliation: Grupo INTERFASE, Universidad Industrial de Santander, Ciudad Universitaria, Bucaramanga, Colombia.
authors.forename: Gilles H
authors.initials: GH
authors.lastname: Gauthier
authors.affiliation: Cryssmat-Lab/Cátedra de Física/DETEMA, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Suescun
mesh_terms: D000977:Antiparasitic Agents / Q000737:chemistry* / Q000494:pharmacology; D001552:Benzazepines / Q000737:chemistry* / Q000494:pharmacology; D014355:Chagas Disease / Q000188:drug therapy; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D018314:Leishmania infantum / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy; D008958:Models, Molecular; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology; D044367:Phase Transition; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D000977:Antiparasitic Agents; D001552:Benzazepines; D009281:Naphthalenes
keywords: antiparasitic activity; benzazepine derivatives; crystal structure; discrete disorder; phase transition; reaction pathway