Abstract
A cariprazine, an oral atypical antipsychotic acting as a D2 and D3 receptor partial agonist, has been crystallized as a free base, trans-N-{4-[2-[4-(2,3-dichlorophenyl)piperazine-1-yl]ethyl]cyclohexyl}-N',N'-dimethylurea, C21H32Cl2N4O (I), and as a chloride salt, trans-N-{4-[2-[4-(2,3-dichlorophenyl)piperazine-1-yl]ethyl]cyclohexyl}-N',N'-dimethylurea hydrochloride, C21H33Cl2N4O+Cl– (II). In both structures, the cariperazine molecule is in an extended conformation. The dimethylurea group exhibits a syn conformation of the O atoms in the I, whereas an almost anti orientation is present in the II. Two terminal groups, dimethylurea and dichlorophenyl ring, are oriented differently in the I and II. The cariprazine molecules in the I are linked into an infinite zigzag chains by N–H···O hydrogen bonds, where the neighboring cariprazine molecules form an L-shape configuration. In the II, the molecules of cariprazine are connected with the chloride anion by N–H···Cl charge-assisted hydrogen bonds, which are further stabilized by weak intermolecular interactions, forming horizontal molecular chain along the b axis. This study reveals the variations in the solid-state conformation of cariprazine molecule in different crystalline environments.
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ACKNOWLEDGMENTS
This work would not have been possible without the effort and encouragement of several individuals of my colleagues. The authors thank Prof. Linshen Chen from Department of Chemistry of Zhejiang University for his kindly help on the DSC analysis.
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Jiali Ye, Liu, K., Zhou, X. et al. Crystal Structures and Thermodynamic Properties of New Atypical Antipsychotic Cariprazine and Its Hydrochloride. Crystallogr. Rep. 63, 930–936 (2018). https://doi.org/10.1134/S1063774518060147
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DOI: https://doi.org/10.1134/S1063774518060147