Unii-o0p4I5851i

The Uses of Unii-o0p4I5851i

An antipsychotic used for treatment of schizophrenia.

Clinical Use

Lurasidone hydrochloride is an antipsychotic developed by the Japanese firm Dainippon Sumitomo and approved by the U.S. FDA for the treatment of schizophrenia. The compound exhibits significant antagonist effects at the D2, 5-HT2A, and 5-HT7 receptors which are linked to learning and cognition. In contrast to available antipsychotics, lurasidone lacks anticholinergic side effects, giving it an improved safety profile against existing treatments.139 The drug is manufactured under the trade name Latuda and possesses a linear molecular topology which can be subdivided into three regions: a piperazine benzothiazole, a [2.2.1]-bicycloheptane fused succinimide, and a trans-1,2 disubstituted cyclohexane.

Synthesis

The large scale preparation of lurasidone involves an interesting ring-opening alkylation reaction of a spirocyclic tetralkyl ammonium salt to produce the 1,2-trans-substituted cyclohexane subunit. The synthesis commenced with the bismesylation of commercially available diol 177, which proceeded in high yield to give disulfone 178. This bis-electrophile underwent dialkylation with commercially available piperazine 179 under basic conditions, giving rise to ammonium species 180, isolated in 80% yield as the mono-mesylate salt. This compound was immediately subjected to alkylative conditions in the presence of commercially available succinimide 181 to provide lurasidone in 94% yield from 180, and lurasidone hydrochloride (XVI) was achieved by subsequent salt formation procedure.