Pridopidine hydrochloride (Huntexil, Neuro-Search A/S, Ballerup, Denmark) is a dopaminergic stabilizer, currently in development for the treatment of motor symptoms associated with Huntington's disease. In this study, two polymorphic forms are characterized, forms I and II. The crystal structures of both polymorphs contain Nand the polymorphism can be viewed as alternative orientations (parallel or antiparallel) of comparable molecular columns while retaining theForms I and II have melting points of 199 and 210 °C, respectively. Following melting of form I, a kinetically controlled crystallization to form II is observed. The polymorphs are enantiotropically related, form I being stable at ambient conditions and form II being stable above 127 °C. At around 180 °C, the differential scanning calorimetry thermogram of a mixture of forms I and II shows a solid-state transition from form I to form II, which is not observed for pure form I samples. Transformation of form II to form I below the transition temperature is solution-mediated. Because of the thermodynamic relation and the propensity for transformations, the safety, quality, and efficacy of pridopidine hydrochloride is not affected by the existence of form II.

(−)-3-(2-Benzothienyl)-8-H-8-azabicyclo[3,2,1]oct-2-ene acetate, NS9544 acetate, is a candidate drug intended to treat pain and other CNS disorders. In the synthetic route tropinone was enantioselective deprotonated with a chiral lithium amide derived from [R-(R*,R*)]-bis(α-methylbenzyl)amine hydrochloride. The formed enolate was trapped as triflate and coupled with benzo[b]thiophene-2-boronic acid under Suzuki conditions. To further enhance the enantiomeric purity crystallisation with l-(+)-tartaric acid was performed. Finally N-demethylation with trichloroethylchloroformate followed by treatment with acetic acid afforded NS9544 as the acetate salt with high enantiomeric purity.

The title compound, C(15)H(16)NS(+)·C(2)H(3)O(2)(-), has been crystallized as both a pure enantiomer (1S,5R) and a racemate. The racemate crystallizes in the space group Cc, with molecules of opposite handedness related to each other by the action of the c-glide. The enantiomer is essentially isostructural with the racemate, except that the glide symmetry is violated by interchange of CH and CH(2) groups within the seven-membered ring. The space-group symmetry is reduced to P1 with two molecules in the asymmetric unit. The enantiomer structure shows disorder of the thiophene ring for one of the molecules in the asymmetric unit. The major component of the disorder has the thiophene ring in the same position as in the racemate, but generates a higher-energy molecular conformation. The minor disorder component has different intermolecular interactions but retains a more stable molecular conformation.