Novel 5-Hydroxytryptamine (5-HT_3) Receptor Antagonists. IV. 1) Synthesis and Pharmacological Evaluation of the Oxidation Products of (-)-(R)-5-[(1-Methyl-1H-indol-3-y1)carbonyl]-4, 5, 6, 7-tetrahydro-1H-benzimidazole Hydrochloride (YM060: Ram osetron)

参考文献11件

この論文をさがす

抄録

In physicochemical and pharmacokinetic evaluations of (-)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride 1 (YM060 : ramosetron), which is a highly potent 5-hydroxytryptamine (5-HT_3) receptor antagonist, 4-hydroxy-6-[(1-methyl-1H-indol-3-yl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole 2 was identified as a degradation product and metabolite of 1. The (-)-(4R, 6S)-isomer 2 was synthesized from the diketone derivative 3,via the stereoselective reduction of 3 followed by the stereocontrolled epimerization of the (-)-(4S, 6S)-isomer 10,the epimer of 2. The stereochemistry of 2 and 10 was determined by NMR and HPLC studies. Compounds 2 and 10 were found to be potent 5-HT_3 receptor antagonists, like 1. Among the other oxidation products, the diketone derivatives 3 and 7 and the dihydroxylated derivative 4 retained antagonistic activity similar to that of ondansetron. This is of interest, because they do not possess the amine group which is known to be necessary for high affinity to the 5-HT_3 receptor.

収録刊行物

参考文献 (11)*注記

もっと見る

キーワード

詳細情報 詳細情報について

  • CRID
    1570572702395222656
  • NII論文ID
    110003632151
  • NII書誌ID
    AA00602100
  • ISSN
    00092363
  • 本文言語コード
    en
  • データソース種別
    • CiNii Articles

問題の指摘

ページトップへ