Sertindole analogs

Gomplex field-based 3-D QSAR models have also been applied to the problem of predicting hERG activity. Gavalli ef al. [85] used a CoMFA model, as previously discussed. Pearlstein ef al. [89] modeled a set of sertindole analogs using compara-... 

Sertindole(94)was selected from a series of N-phenylindolyl-piperidines and has K s of 0.39 and 4.1 nM at the 5-HT and D2 receptors, respectively, and a favorable ratio of 10.5. Sertindole blocks the hyperactivity in rats induced by dopamine infusion into the nucleus accumbens without causing the rebound hyperactivity after cessation of treatment seen with typical antipsychotics. Although sertindole has a low propensity to induce catalepsy, both the direct analog in which the chloro substituent is replaced by cyano and also the corresponding piperazine and tetrahydropyri-dine analogs have more classical Da/S-HTg ratios favoring D, affinity and thus potently induce catalepsy (592). 

Finally, this reaction motif has been used in the synthesis of analogs of the antipsychotic sertindole for structure-activity relationship (SAR) studies [19]. Specifically, the substitution was effected at the 5-position of the indole nucleus to give analog 21. 

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