Oxatomide, sold under the brand name Tinset among others, is a

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides ...

of the

diphenylmethylpiperazine Diphenylmethylpiperazine, also known as benzhydrylpiperazine, is a chemical compound and piperazine derivative. It features a piperazine ring with a benzhydryl (diphenylmethyl) group bound to one of the nitrogens. Cyclizine, an antihistamine and ...

family which is marketed in

Europe Europe is a continent located entirely in the Northern Hemisphere and mostly in the Eastern Hemisphere. It is bordered by the Arctic Ocean to the north, the Atlantic Ocean to the west, the Mediterranean Sea to the south, and Asia to the east ...

Japan Japan is an island country in East Asia. Located in the Pacific Ocean off the northeast coast of the Asia, Asian mainland, it is bordered on the west by the Sea of Japan and extends from the Sea of Okhotsk in the north to the East China Sea ...

, and a number of other countries. It was discovered at

Janssen Pharmaceutica Johnson & Johnson Innovative Medicine (formerly Janssen Pharmaceuticals) is a Belgian pharmaceutical company headquartered in Beerse, Belgium, and wholly owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen. In 1961, Janssen Ph ...

in 1975. Oxatomide lacks any

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system. These agents inhibit the parasympatheti ...

effects. In addition to its H₁ receptor antagonism, it also possesses

antiserotonergic A serotonin antagonist, or serotonin receptor antagonist, is a drug used to inhibit the action of serotonin and serotonergic drugs at serotonin (5-HT) receptors. Types 5-HT2A antagonists Antagonists of the 5-HT2A receptor are sometimes used ...

activity similarly to

hydroxyzine Hydroxyzine, sold under the brand names Atarax and Vistaril among others, is an antihistamine medication. It is used in the treatment of itchiness, anxiety, insomnia, and nausea (including that due to motion sickness). It is used either by mou ...

. Oxatomide was also found to have

antiviral Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials ...

activity against Venezuelan equine encephalitis virus ( VEEV). It was patented in 1976 and came into medical use in 1981.

Chemistry

Synthesis

Reaction of

2-Benzimidazolinone Benzimidazolinone is an organic compound with the formula . Also classified as a heterocyclic compound it is a bicyclic urea. It is a tautomer of 2-hydroxybenzimidazole. Synthesis, structure, applications The parent compound is prepared by th ...

with

isopropenyl acetate Isopropenyl acetate is an organic compound, which is the acetate ester of the enol tautomer of acetone. This colorless liquid is significant commercially as the principal precursor to acetylacetone. In organic synthesis, it is used to prepare en ...

leads to the singly protected imidazolone derivative (2).

Alkylation Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...

of this with 3-chloro-1-bromopropane affords the functionalized derivative (3). Alkylation of the monobenzhydryl derivative of

piperazine Piperazine () is an organic compound with the formula . In term of its structure, it can be described as cyclohexane with the 1- and 4-CH2 groups replaced by NH. Piperazine exists as deliquescent solid with a saline taste. Piperazine is freely sol ...

(4) with 3 gives oxatomide (5), after hydrolytic removal of the

protecting group A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis. In man ...

References

Benzimidazoles Belgian inventions H1 receptor antagonists Janssen Pharmaceutica Gamma-lactams Cyclizines Ureas {{Respiratory-system-drug-stub