Isothiazoles. Part XV. A mild and efficient synthesis of new antiproliferative 5-sulfanylsubstituted 3-alkylaminoisothiazole 1,1-dioxides

F. Clerici, A. Contini, A. Corsini, N. Ferri, S. Grzesiak, S. Pellegrino, A. Sala, K. Yokoyama

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

5-Sulfanyl-3-alkylaminoisothiazole dioxide derivatives have been identified as a new class of potent inhibitors of rat aortic myocite proliferation. They were prepared by applying a simple methodology able to introduce a heteroatom on C-5 of the 3-alkylaminoisothiazole dioxide system. 3-Aminosubstituted-5-chloroisothiazole dioxides react smoothly not only with S-nucleophiles but also with N- and O-nucleophiles affording the corresponding 5-heterosubstituted isothiazole dioxides through an addition-elimination reaction. The behavior of 3-alkylamino-4-bromo-isothiazole 1,1-dioxide with S-, N- and O-nucleophiles affording the same products has also been described. On the contrary, the 3-amino-4,5-unsubstituted isothiazole dioxide system reacts easily only with sulfur nucleophiles affording the corresponding 4,5-dihydro-5-sulfanylderivatives through a simple Michael addition reaction.

Original languageEnglish
Pages (from-to)675-682
Number of pages8
JournalEuropean Journal of Medicinal Chemistry
Volume41
Issue number5
DOIs
Publication statusPublished - May 2006

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Nucleophiles
Sulfur
Addition reactions
Rats
Derivatives

Keywords

  • Farnesyl transferase
  • Isothiazoles
  • Nucleophilic addition
  • Smooth muscle cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Isothiazoles. Part XV. A mild and efficient synthesis of new antiproliferative 5-sulfanylsubstituted 3-alkylaminoisothiazole 1,1-dioxides. / Clerici, F.; Contini, A.; Corsini, A.; Ferri, N.; Grzesiak, S.; Pellegrino, S.; Sala, A.; Yokoyama, K.

In: European Journal of Medicinal Chemistry, Vol. 41, No. 5, 05.2006, p. 675-682.

Research output: Contribution to journalArticle

Clerici, F. ; Contini, A. ; Corsini, A. ; Ferri, N. ; Grzesiak, S. ; Pellegrino, S. ; Sala, A. ; Yokoyama, K. / Isothiazoles. Part XV. A mild and efficient synthesis of new antiproliferative 5-sulfanylsubstituted 3-alkylaminoisothiazole 1,1-dioxides. In: European Journal of Medicinal Chemistry. 2006 ; Vol. 41, No. 5. pp. 675-682.
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