Ketanserin analogues

Fig. 24.3 Structural formulae of 5-HT2a antagonists used for pharmacophore identification (a) ketanserin analogues (b) spiperone analogues (c) cyproheptadiene analogues (d) irindalone analogues.

Herndon, J.L., Ismaiel, A., Ingher, S.P., Teitler, M, and Glennon, R.A. (1992) Ketanserin analogues structure-affinity relationships for S-HTa and 5-HTic serotonin receptor binding. J. Med. Chem. 35 4903-4910. 

Elz, S (1992) Synthesis and in vitro pharmacology of antisero-toninergic2 ketanserin analogues and N-imidazolyalkyl substituted 4-(4-fluorobenzoyl)piperidine- 1-carboxamidines. Xllth International Symposium on Medicinal Chemistry, Basel, Switzerland, poster-128.C, abstract book, p. 349. 

C-A -Methylketanserin 279, the analogue of serotonin-2 receptor antagonist, ke-tanserin 280, has been synthesized for studying these receptors in vivo using PET by alkylation of ketanserin in DMF solution in the presence of small amount of aqueous tetrabutylammonium hydroxide at 80 °C for 2 minutes followed by chromatographic purification during 22 minutes total synthesis time from EOB, with 10% radiochemical yield calculated at the end of synthesis (EOS). 

Replacement of the benzylic carbonyl oxygen of ketanserin by hydrogen or phenyl reduces affinity 5 fold [11,12], For the phenylethyl- and phenylbutyl analogues is the decrease in affinity 2 and 12 times respectively [12],... 

Reduction of the benzylic carbonyl group of desfluoro-ketanserin decreases the affinity for S-HTjy receptors 100 times [11] (Table 4). The N-ethyl substituted analogue even lost all affinity. However contrary to the expectations high affinity is maintained in the phenylethyl derivatives [12] (Table 4). 

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