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

first-generation antihistamine H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of hi ...

of the

diphenylmethylpiperazine 1-(Diphenylmethyl)piperazine, also known as benzhydrylpiperazine, is a chemical compound and piperazine derivative. It features a piperazine ring with a benzhydryl (diphenyl methyl) group bound to one of the nitrogen Nitrogen is the chemical ...

family which is marketed in

Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a subcontinent of Eurasia and it is located entirel ...

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

Janssen Pharmaceutica Janssen Pharmaceuticals is a pharmaceutical company headquartered in Beerse, Belgium, and wholly-owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen. In 1961, Janssen Pharmaceuticals was purchased by New Jersey-based American ...

in 1975. Oxatomide lacks any

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

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

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

. It was patented in 1976 and came into medical use in 1981.

Chemistry

Synthesis

Reaction of 2-Benzimidazolinone with isopropenyl acetate leads to the singly protected imidazolone derivative (2).

Alkylation Alkylation is the transfer of an alkyl group from one molecule to another. 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 effecti ...

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

piperazine Piperazine () is an organic compound that consists of a six-membered ring containing two nitrogen atoms at opposite positions in the ring. Piperazine exists as small alkaline deliquescent crystals with a saline taste. The piperazines are a broad ...

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

References

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