Oxatomide Explained

Oxatomide, sold under the brand name Tinset among others, is a antihistamine of the diphenylmethylpiperazine family which is marketed in Europe, Japan, and a number of other countries.^{[1] [2] [3] [4]} It was discovered at Janssen Pharmaceutica in 1975.^[5] Oxatomide lacks any anticholinergic effects.^[2] In addition to its H₁ receptor antagonism, it also possesses antiserotonergic activity similarly to hydroxyzine.^[2]

It was patented in 1976 and came into medical use in 1981.^[6]

Chemistry

Synthesis

Reaction of 2-Benzimidazolinone with isopropenyl acetate leads to the singly protected imidazolone derivative (2). Alkylation of this with 3-chloro-1-bromopropane affords the functionalized derivative (3). Alkylation of the monobenzhydryl derivative of piperazine (4) with 3 gives oxatomide (5), after hydrolytic removal of the protecting group.

Notes and References

1. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014. Springer. 978-1-4757-2085-3. 912–.
2. Ohmori K, Ishii H, Nito M, Shuto K, Nakamizo N . [Pharmacological studies on oxatomide (KW-4354). (7) Antagonistic effects on chemical mediators] . ja . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica . 81 . 5 . 399–409 . May 1983 . 6138301 . 10.1254/fpj.81.399 . free .
3. Book: Index Nominum 2000: International Drug Directory. 2000. Taylor & Francis. 978-3-88763-075-1. 768–.
4. Web site: Oxatomide . Drugs.com .
5. Book: Schwartz H . Breakthrough: the discovery of modern medicines at Janssen. registration. August 1989. Skyline Pub. Group. 978-1-56019-100-1. 149.
6. Book: Fischer J, Ganellin CR . Analogue-based Drug Discovery . 2006 . John Wiley & Sons . 9783527607495 . 548 . en.