Microwave-assisted regioselective direct C-H arylation of thiazole derivatives leading to increased σ1 receptor affinity

Artur Kokornaczyk, Dirk Schepmann, Junichiro Yamaguchi, Kenichiro Itami, Bernhard Wünsch*

*この研究の対応する著者

研究成果: Article査読

14 被引用数 (Scopus)

抄録

New thiazole analogues 2 of spirocyclic thiophenes 1, which are known to show high σ1 receptor affinities, have been developed as potentially better σ1 receptor ligands. To introduce an aryl group onto the thiazole core of 2 (C4 or C5 positions), we used Pd-catalyzed regioselective C-H arylation reactions. The Pd-catalyzed C5 arylation of 2a could be considerably improved by using microwave irradiation technique. The Pd-catalyzed C4 arylation of thiazole 2a with arylboronic acid 6 could be achieved in the presence of Pd(OAc)2, 1,10-phenanthroline, TEMPO, and LiBF4. Under these conditions, the tertiary amine and the tertiary alcohol were well-tolerated. The regioselective arylation of 2a led to new compounds 2b and 2c, with a 4-tolyl moiety in the C5- and C4-positions, displaying five to nine-fold increased σ1 affinity. The same σ1 affinity of the regioisomeric thiazoles 2b and 2c can be explained by fast rotation around the piperidine-thiazole bond. Compared to spirocyclic thiophenes 1, thiazoles 2 are considerably more polar.

本文言語English
ページ(範囲)327-331
ページ数5
ジャーナルMedChemComm
7
2
DOI
出版ステータスPublished - 2016 2月 1
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 薬科学

フィンガープリント

「Microwave-assisted regioselective direct C-H arylation of thiazole derivatives leading to increased σ1 receptor affinity」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル