Oxatomide

Oxatomide

Above: molecular structure of oxatomide Below: 3D representation of an oxatomide molecule
Clinical data
Trade names	Tinset, others
Other names	KW-4354; McN-JR 35443; R-35443
AHFS/Drugs.com	International Drug Names
Routes of administration	By mouth
ATC code	R06AE06 ( WHO )
Legal status
Legal status	In general: ℞ (Prescription only)
Identifiers
IUPAC name 1-{3-[4-(diphenylmethyl)piperazin-1-yl]propyl}-1,3-dihydro-2H-benzimidazol-2-one
CAS Number	60607-34-3  N
PubChem CID	4615
ChemSpider	4454  Y
UNII	J31IL9Z2EE
KEGG	D01773  Y
ChEBI	CHEBI:31943
ChEMBL	ChEMBL13828  Y
CompTox Dashboard (EPA)	DTXSID4045181
ECHA InfoCard	100.056.637
Chemical and physical data
Formula	C27H30N4O
Molar mass	426.564 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C2Nc1ccccc1N2CCCN5CCN(C(c3ccccc3)c4ccccc4)CC5
InChI InChI=1S/C27H30N4O/c32-27-28-24-14-7-8-15-25(24)31(27)17-9-16-29-18-20-30(21-19-29)26(22-10-3-1-4-11-22)23-12-5-2-6-13-23/h1-8,10-15,26H,9,16-21H2,(H,28,32) Y Key:BAINIUMDFURPJM-UHFFFAOYSA-N Y
NY  (what is this?)    (verify)

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] Oxatomide was also found to have antiviral activity against Venezuelan equine encephalitis virus (VEEV). ^[6]

It was patented in 1976 and came into medical use in 1981. ^[7]

Chemistry

Synthesis

Oxatomide 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.

References

1. Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 912–. ISBN   978-1-4757-2085-3.
2. Ohmori K, Ishii H, Nito M, Shuto K, Nakamizo N (May 1983). "[Pharmacological studies on oxatomide (KW-4354). (7) Antagonistic effects on chemical mediators]". Nihon 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". Drugs.com.
5. Schwartz H (August 1989). Breakthrough: the discovery of modern medicines at Janssen . Skyline Pub. Group. p.  149. ISBN   978-1-56019-100-1.
6. Hu X, Morazzani E, Compton JR, Harmon M, Soloveva V, Glass PJ, et al. (July 2023). "In Silico Screening of Inhibitors of the Venezuelan Equine Encephalitis Virus Nonstructural Protein 2 Cysteine Protease". Viruses. 15 (7): 1503. doi: 10.3390/v15071503 . PMC   10385868 . PMID   37515189.
7. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 548. ISBN   9783527607495.
8. DE 2714437,Vandenberk J, Kennis LE, Van der Aa MJ, Van Heertum AH,"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  
9. US 4250176,Vandenberk J, Kennis LE, Van der Aa MJ, Van Heertum AH,issued 10 February 1981, assigned to Janssen Pharmaceutica NV.