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

Oxatomide synthesis:[7][8]

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.

References

  1. ^ J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 912–. ISBN 978-1-4757-2085-3.
  2. ^ a b c Ohmori K, Ishii H, Nito M, Shuto K, Nakamizo N (May 1983). "[Pharmacological studies on oxatomide (KW-4354). (7) Antagonistic effects on chemical mediators]". Nippon Yakurigaku Zasshi. Folia Pharmacologica Japonica (in Japanese). 81 (5): 399–409. doi:10.1254/fpj.81.399. PMID 6138301.
  3. ^ Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 768–. ISBN 978-3-88763-075-1.
  4. ^ "Oxatomide".
  5. ^ Harry Schwartz (August 1989). Breakthrough: the discovery of modern medicines at Janssen. Skyline Pub. Group. p. 149. ISBN 978-1-56019-100-1.
  6. ^ Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 548. ISBN 9783527607495.
  7. ^ DE 2714437, Vandenberk, Jan; Kennis, Ludo E.J. & van der Aa, Marcel J.M.C. et al., "Piperazin- und Piperidinderivate, Verfahren zu ihrer Herstellung und Arzneipräparate [Piperazine and piperide derivatives, procedures for their manufacturing and medicinal preparations]", published 1977-10-20, assigned to Janssen Pharmaceutica 
  8. ^ J. Vandenberk et al., U.S. Patent 4,250,176 (1981 to Janssen).