MISC

2003年8月

Stereoselective synthesis and structure-activity relationship of novel ceramide trafficking inhibitors. (1R,3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide and its analogues

JOURNAL OF MEDICINAL CHEMISTRY
  • Y Nakamura
  • ,
  • R Matsubara
  • ,
  • H Kitagawa
  • ,
  • S Kobayashi
  • ,
  • K Kumagai
  • ,
  • S Yasuda
  • ,
  • K Hanada

46
17
開始ページ
3688
終了ページ
3695
記述言語
英語
掲載種別
DOI
10.1021/jm0300779
出版者・発行元
AMER CHEMICAL SOC

New ceramide trafficking inhibitors, (1R,3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide (HPA-12) and a series of its analogues, were synthesized in diastereomerically and enantiomerically pure forms, and the structure-activity relationship was investigated. These analogues were stereoselectively synthesized via catalytic enantioselective Mannich-type reactions using a Cu(II)-chiral diamine 4 complex. Analysis of HPA-12 analogues having various lengths of the amide side chain showed that the optimal chain length for the inhibition of sphingomyelin biosynthesis is 13 with an IC50 of similar to50 nM. Masking of the hydroxy group at the 2'- or 3-position of HPA-12 was carried out by methylation, and it was revealed that these hydroxy groups were essential for the activity. Installation of another hydroxy group onto HPA-12 at the same position as that in the natural ceramide was also conducted, but no enhancement of the activity was observed.

リンク情報
DOI
https://doi.org/10.1021/jm0300779
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000184719100016&DestApp=WOS_CPL
ID情報
  • DOI : 10.1021/jm0300779
  • ISSN : 0022-2623
  • Web of Science ID : WOS:000184719100016

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