Clocinizine

Clocinizine

Clinical data
Trade names	Senioral (with PPATooltip phenylpropanolamine)
AHFS/Drugs.com	International Drug Names
Routes of administration	By mouth
ATC code	none
Identifiers
IUPAC name 1-[(4-chlorophenyl)-phenylmethyl]-4-[(E)-3-phenylprop-2-enyl]piperazine
CAS Number	298-55-5
PubChem CID	5375618
ChemSpider	4525064
UNII	8HQJ711KH8
ChEMBL	ChEMBL2104069
Chemical and physical data
Formula	C26H27ClN2
Molar mass	402.97 g·mol^−1
3D model (JSmol)	Interactive image
SMILES Clc1ccc(cc1)C(c2ccccc2)N3CCN(CC3)C\C=C\c4ccccc4

Clocinizine is a first-generation antihistamine of the diphenylmethylpiperazine class. It is marketed in Spain in combination with phenylpropanolamine under the brand name Senioral.^[1]

Synthesis

Synthesis:^[2] Patent:^[3]

The reduction of 4-Chlorobenzophenone [134-85-0] (1) with NBH gives 4-Chlorobenzhydrol [119-56-2] (2). Halogenation of the alcohol in muriatic acid afforded 4-Chlorobenzhydryl chloride [134-83-8] (3). Alkylation with one equivalent of piperazine gives 1-(4-Chlorobenzhydryl)piperazine [303-26-4] (4). Alkylation of the remaining nitrogen with Cinnamyl Bromide [4392-24-9] (5) completed the synthesis of Clocinizine (6).

References

1. Fookes C (September 2022). "List of Common Antihistamines + Uses & Side Effects". Drugs.com.
2. Venkat Narsaiah A, Narsimha P (April 2012). "Efficient synthesis of antihistamines clocinizine and chlorcyclizine". Medicinal Chemistry Research. 21 (4): 538–541. doi:10.1007/s00044-011-9556-x. S2CID 253636495.
3. DE 2220242, Kato H, Kurata S, "Antiarrhythmic piperazine derivs prepn - from benzhydrylpiperazine cinnamaldehyde by leuckart reaction", issued 1972, assigned to Hokuriku Pharmaceutical