Crystallographic study of diarylazoles related to rimonabant

Abstract

Rimonabant is the first selective CB1 receptor blocker used in patients of metabolic syndrome and related illness like diabetes and dyslipidaemia. There is a great interest on the polymorphism of Rimonabant and related compounds. The structures of Rimonabant [1] and three diarylazoles [2] (two pyrazoles and one 1,2,4-triazole) related to Rimonabant have been determined by X-ray diffraction. These studies will provide other researches in the active field of cannabinoid antagonist with the molecular properties of the reference compound. Data from Rimonabant were collected at 293K and at 150K in a Xcalibur Nova diffractometer. The structure of the methanol solvate of Rimonabant displays no noticeable modifications in crystal packing from RT to 150K. It is monoclinic and the space group is P21/c. The solvate molecule helps to the packing connecting two Rimonabant molecules throughout the -N-H…O-H…O-synthon, forming infinite chains propagating along the b crystallographic axis. Two additional C-H…O-weak interactions were better located in the low temperature experiment. In this work, we will show the crystal data and structure refinement of Rimonabant at both temperatures. Further details of the X-ray structural analysis will be given and exhaustive hydrogen bonding geometry study will be discussed. Acknowledgments: Financial support from Spanish Ministery of Science and Technology (MAT2006-01997, CTQ2007-61901/BQU and 'Factoría de Cristalización' Consolider Ingenio 2010) and FEDER founding is acknowledged.[1] Alkorta I., Alvarado M., Elguero J., García-Granda S., Goya P., Jimeno M.L., Menéndez-Taboada L. Eur. J. Mol. Chem. In press.[2] Alkorta I., Alvarado M., Elguero J., García-Granda S., Goya P., Torre-Fernández L., Menéndez-Taboada L. (1) is the first selective CB 1 receptor blocker used in many countries for patients with metabolic syndrome and related illnesses, like diabetes and dyslipidaemia. The unknown structure of 1 was recently determined by our research group [1]. It is worth mentioning the increasing interest on the polymorphs of 1 and related compounds. A large series of compounds related to 1 was prepared and evaluated. Ethyl 5-(4-chlorophenyl)-1-phenylpyrazole-3-carboxylate (2), N-(1-hexadecyl)-1,5-bis(4-chlorophenyl)-1H-pyrazole-3-carboxamide (3) and methyl 1,5-bis(4-chlorophenyl)-1H-1,2,4-triazole-3-carboxilate (4) are three of these compounds. In this communication we deal with the structures of the three diarylazoles exhibing a very different secondary structure [2]. The crystal packing of compound 2 shows a helix type propagation along the c axis supported by a weak H-bond, involving nitrogen and carbon. The molecular packing of compound 3 is made up of a network of hydrogen bonding interactions stabilizing hydrocarbon layers parallel to bc plane. Within the layers the aromatic rings are stacked. The molecular structure of compound 4 contains two forms of hydrogen bonds: the O···H bonds along the chain and the O···H bonds between chains packing like a double chain. The double chain is packed b...