Xaliproden hydrochloride

Originator

Xaliproden hydrochloride,Sanofi (Sanofi- Aventis)

The Uses of Xaliproden hydrochloride

Xaliproden is a 5-HT1A agonist used in the treatment of allodynia.

What are the applications of Application

Xaliproden hydrochloride is a full agonist of SR-1A

Definition

ChEBI: Xaliproden hydrochloride is a member of naphthalenes.

Manufacturing Process

A solution of 27.8 kg of 2-naphthylacetic acid in 95 L of tetrahydrofuran is added, at a temperature below 20°C to a mixture of 27.5 L of tetrahydrofuran and 10.0 kg of lithium aluminum hydride. The mixture is cooled to 0°C and the following are then added slowly: firstly 10 L of water, then a solution of 1.5 kg of sodium hydroxide in 10 L of water, and finally 30 L of water. The salts which separate out are washed with 160 L of tetrahydrofuran and then filtered off. The combined tetrahydrofuran solutions are evaporated and the 24.5 kg of 2-(2-naphthyl)ethanol are obtained.
The 2-(2-naphthyl)ethanol is treated with 138 L of concentrated hydrobromic acid. The mixture is refluxed for 5 h and allowed to return to room temperature, with stirring, and the product obtained is then filtered off and washed with water. The moist product is dissolved in 147 L of isopropanol under reflux, about 75 L of solvent are removed by distillation and the mixture is allowed to cool overnight. The product which has crystallized is filtered off, washed with previously cooled isopropanol and dried under vacuum at 40°C. So the 2-(2-bromoethyl)naphthalene is obtained (yield: 81%, calculated relative to the starting naphthylacetic acid).
A mixture of 12.5 g of 2-(2-bromoethyl)naphthalene, 14.0 g of 4-(3- trifluoromethylphenyl)-1,2,3,6-tetrahydropyridine hydrochloride, 4.34 g of sodium hydroxide, 135 ml of water and 95 ml of 95% ethanol is refluxed for 5 h, the reaction mixture is subsequently allowed to cool to room temperature overnight and then filtered and the product isolated in this way is washed with water and dried under vacuum at 50°C to give 1-[2-(2-naphthyl)ethyl]-4-(3- trifluoromethylphenyl)-1,2,3,6-tetrahydropyridine (yield of 90%, calculated relative to the starting 4-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydropyridine hydrochloride).

Therapeutic Function

Serotonin antagonist, Nootropic

Biological Activity

Orally active, full agonist at 5-HT 1A receptors. Binds rat 5-HT 1A with high affinity (K i = 2.0 nM) and is > 300-fold selective over other 5-HT receptor subtypes (IC 50 > 650 nM). Increases motoneuron survival and promotes effects of NGF on neurite outgrowth in vitro . Displays neurotrophic activity in several neurodegenerative models in vivo .