169774-61-2Relevant academic research and scientific papers
Synthesis and biological evaluation of (-)-kainic acid analogues as phospholipase D-coupled metabotropic glutamate receptor ligands
Zanato, Chiara,Watson, Sonia,Bewick, Guy S.,Harrison, William T. A.,Zanda, Matteo
, p. 9638 - 9643 (2015/02/19)
(-)-Kainic acid potently increases stretch-induced afferent firing in muscle spindles, probably acting through a hitherto uncloned phospholipase D (PLD)-coupled mGlu receptor. Structural modification of (-)-kainic acid was undertaken to explore the C-4 substituent effect on the pharmacology related to muscle spindle firing. Three analogues 1a-c were synthesised by highly stereoselective additions of a CF3, a hydride and an alkynyl group to the Re face of the key pyrrolidin-4-one intermediate 5a followed by further structural modifications. Only the 4-(1,2,3-triazolyl)-kainate derivative 1c retained the kainate-like agonism, increasing firing in a dose-dependent manner. Further modification of 1c by introduction of a PEG-biotin chain on the 1,2,3-triazole fragment afforded compound 14 which retained robust agonism at 1 μM and appears to be suitable for future use in pull-down assays and far western blotting for PLD-mGluR isolation. This journal is
Towards a versatile synthesis of kainoids I: Introduction of the C-3 and C-4 substituents
Baldwin, Jack E.,Bamford, Samantha J.,Fryer, Andrew M.,Rudolph, Martin P. W.,Wood, Mark E.
, p. 5233 - 5254 (2007/10/03)
The first stages in the synthesis of acromelic acid analogues from trans-4-hydroxy-L-proline are described. An enamine alkylation was used to stereospecifically introduce the C-3 substituent, Grignard addition to a ketone or Pd(0) catalysed cross-coupling procedures adding C-4 aryl substituents for further manipulation. A number of versatile intermediates were generated.
