Structure of racemic duloxetine hydro-chloride.

Duloxetine hydro-chloride (trade name Cymbalta) is marketed as a single enanti-omer ( S )- N -methyl-3-(naphthalen-1-yl-oxy)-3-(thio-phen-2-yl)propyl-am-in-ium chloride, C 18 H 20 NOS + ·Cl - , which is twice as effective as the ( R )-enanti-omer in serotonin uptake. Here, we report the crystal structure of duloxetine hydro-chloride in its racemic form (space group Pna 2 1 ), where it shows significant differences in the mol-ecular conformation and packing in its extended structure compared to the previously reported ( S )-enanti-omer crystal structure. Mol-ecules of this type, comprising aromatic groups with a single side chain terminated in a protonated secondary amine, are commonly found in active anti-depressants. A Cambridge Structural Database survey of mol-ecules with these features reveals a strong correlation between side-chain conformation and the crystal packing: an extended side chain leads to mol-ecules packed into separated layers of hydro-phobic and ionic hydro-philic phases. By comparison, mol-ecules with bent side chains, such as racemic duloxetine hydro-chloride, lead to crystal-packing motifs where an ionic hydro-philic phase is encapsulated within a hydro-phobic shell.