ChemInform Abstract: Syntheses of 4‐(Benzo(b)furan‐2 or 3‐yl)‐ and 4‐(Benzo(b)thiophen‐3‐yl) piperidines with 5‐HT2 Antagonist Activity.

Watanabe, Yoshiaki; Yoshiwara, H.; Kanao, Munefumi

doi:10.1002/chin.199338208

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“…The desired core piperidine building blocks have been used frequently before for synthesis and are described in the literature, ,,,,− but many of them are also commercially available (Scheme ): 6-fluoro-3-(4-piperidyl)-1 H -indole, 5-fluoro-3-(4-piperidyl)-1 H -indole, 4-(benzofuran-3-yl)piperidine, 6-fluoro-3-(4-piperidyl)-1,2-benzoxazole, 1-(4-piperidyl)indole, 1-(4-piperidyl)benzimidazole, 6-chloro-3-(4-piperidyl)-1 H -benzimidazol-2-one, 4-(2-naphthyl)piperidine, and 4-(1-naphthyl)piperidine. The piperidines were alkylated with iodopropane, affording the desired products 9 , 10 (5-fluoro-3-(1-propyl-4-piperidyl)-1 H -indole), 14 , 15 , 17 – 19 , and 22 – 23 in moderate–good yields (26–87%, Scheme ).…”

Section: Chemistrymentioning

confidence: 99%

Systematic in Vivo Screening of a Series of 1-Propyl-4-arylpiperidines against Dopaminergic and Serotonergic Properties in Rat Brain: A Scaffold-Jumping Approach

Mattsson¹,

Andreasson²,

Waters³

et al. 2012

J. Med. Chem.

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A series of 1-propyl-4-arylpiperidines were synthesized and their effects on the dopaminergic and serotonergic systems tested in vivo and in vitro. Scaffold jumping among five- and six-membered bicyclic aryl rings attached to the piperidine ring had a marked impact on these effects. Potent and selective dopamine D(2) receptor antagonists were generated from 3-indoles, 3-benzoisoxazoles, 3-benzimidazol-2-one, and 3-benzothiophenes. In contrast, 3-benzofuran was a potent and selective inhibitor of monoamine oxidase (MAO) A. The effects of the synthesized compounds on 3,4-dihydroxyphenylacetic acid (DOPAC) levels correlated very well with their affinity for dopamine D(2) receptors and MAO A. In the 4-arylpiperidine series, the most promising compound for development was the 6-chloro-3-(1-propyl-4-piperidyl)-1H-benzimidazol-2-one (19), which displayed typical dopamine D(2) receptor antagonist properties in vivo but produced only a partial reduction on spontaneous locomotor activity. This indicates that the compound may have a lower propensity to induce parkinsonism in patients.

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