3-Methyl-7-phenyl-6-oxa-3-azabicyclo[6.4.0]dodeca-8,10,12-triene

Originator

Ajan,Kettelhack Riker,W. Germany,1976

Uses

Nefopam is a non-opioid non-steroidal centrally acting analgesic.

Definition

ChEBI: 5-methyl-1-phenyl-3,4,5,6-tetrahydro-1H-2,5-benzoxazocine is a member of the class of benzoxazocines that is 3,4,5,6-tetrahydro-1H-2,5-benzoxazocine substituted by phenyl and methyl groups at positions 1 and 5 respectively. It is a benzoxazocine and a tertiary amino compound.

Manufacturing Process

The starting material is prepared by reacting 2-benzoylbenzoic acid with thionyl chloride and then with 2-methylaminoethanol. 20.0 grams (0.07 mol) of N-(2-hydroxyethyl)-N-methyl-o-benzoylbenzamide is suspended in 100 ml tetrahydrofuran and then slowly added in small portions to a solution of 5.5 grams (0.14 mol) of lithium aluminum hydride in 150 ml tetrahydrofuran with cooling and stirring. The mixture is then refluxed for 18 hours, cooled and then to it is successively added 5.5 ml water, 5.5 ml of 3.75 N sodium hydroxide and 16 ml water. After removal of precipitated salts by filtration, the solution remaining is concentrated under reduced pressure and the residue dried to yield 19.5 grams of crude product. Yield after conversion to the hydrochloride salt and recrystallization is 17.0 grams (89%), MP 128° to 133°C.
5-methyl-1-phenyl-1,3,4,6-tetrahydro-5H-benz[f] -2,5-oxazocine is prepared as follows. 3.0 grams (0.011 mol) of 2-([N-(2-hydroxyethyl)-Nmethyl]amino)methylbenzhydrol, prepared as described above, 3.0 grams ptoluenesulfonic acid and 15 ml benzene are heated together with stirring until all the benzene is distilled off. The residual oil is heated to 105°C and held at this temperature for 1 hour, then cooled and dissolved in 30 ml water. This aqueous solution is then basified to pH 10.0 with 12 N sodium hydroxide, extracted with ether, and the extracts washed with water, dried over anhydrous sodium sulfate and the solvent removed under reduced pressure. The 2.26 grams (81%) oil remaining is converted to the hydrochloride salt, MP 238° to 242°C.

brand name

Acupan (3M Pharmaceuticals).

Therapeutic Function

Muscle relaxant, Antidepressant

Clinical Use

Nefopam is a centrally acting analgesic without opioid properties. It induces inhibition of NA and 5-HT reuptake and has antimuscarinic and sympatomimetic actions which all might be relevant for its analgesic action. Nefopam is used orally and parenterally for the treatment of moderately severe pain. Side effects are nausea, vomiting, sweating, nervousness, tachycardia, and occasionally convulsions. Nefopam should not be used in combination with MAO inhibitors.