- (R)-1,2,3,4-Tetrahydrobenzothienopyridines: Novel Optically Active Compounds with Strong 5-HT1A Receptor Binding Ability Exhibiting Anticonflict Activity and Lessening of Memory Impairment
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(R)-1,2,3,4-Tetrahydrobenzothienopyridine derivatives (60-114) were synthesized.The (R)-isomers have affinity for the 5-HT1A receptor while the (S)-isomers have no such ability.The affinity of the (R)-isomers was discussed on the basis of structure-activity relationships between the affinity and hydrophobicity of the (R)-isomers.Compounds 71 and 107, which are representative derivative compounds, have anticonflict activity and lessening of memory impairment.In particular, compound 107 cannot bind to receptors other than the 5-HT1A receptor, demonstrating that it is a unique compound with a different mechanism of action from that of conventional anxiolytics.
- Kawakubo, Hiromu,Takagi, Seiji,Yamaura, Yuuji,Katoh, Shinichi,Ishimoto, Yumiko,et al.
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- The interaction of heteroaryl-acrylates and alanines with phenylalanine ammonia-lyase from parsley
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Acrylic acids and alanines substituted with heteroaryl groups at the β-position were synthesized and spectroscopically characterized (UV, HRMS, 1H NMR, and 13C NMR spectroscopy). The heteroaryl groups were furanyl, thiophenyl, benzofuranyl, and benzothiophenyl and contained the alanyl side chains either at the 2- or 3-positions. While the former are good substrates for phenylalanine ammonia lyase (PAL), the latter compounds are inhibitors. Exceptions are thiophen-3-yl-alanine, a moderate substrate and furan-3-yl-alanine, which is inert. Possible reasons for these exceptions are discussed. Starting from racemic het eroaryl-2-alanines their D-enantiomers were prepared by using a stereodestructive procedure. From the heteroaryl-2- acrylates, the L-enantiomers of the heteroaryl-2-alanines were prepared at high ammonia concentration. These results can be best explained by a Friedel - Crafts-type electrophilic attack at the aromatic part of the substrates as the initial step of the PAL reaction.
- Paizs, Csaba,Katona, Adrian,Retey, Janos
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p. 2739 - 2744
(2008/02/03)
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