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 language | English |
|---|---|
| Pages (from-to) | 675-682 |
| Number of pages | 8 |
| Journal | European Journal of Medicinal Chemistry |
| Volume | 41 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2006 |
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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 journal › Article
}
TY - JOUR
T1 - Isothiazoles. Part XV. A mild and efficient synthesis of new antiproliferative 5-sulfanylsubstituted 3-alkylaminoisothiazole 1,1-dioxides
AU - Clerici, F.
AU - Contini, A.
AU - Corsini, A.
AU - Ferri, N.
AU - Grzesiak, S.
AU - Pellegrino, S.
AU - Sala, A.
AU - Yokoyama, K.
PY - 2006/5
Y1 - 2006/5
N2 - 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.
AB - 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.
KW - Farnesyl transferase
KW - Isothiazoles
KW - Nucleophilic addition
KW - Smooth muscle cell
UR - http://www.scopus.com/inward/record.url?scp=33746705116&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746705116&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2006.01.009
DO - 10.1016/j.ejmech.2006.01.009
M3 - Article
C2 - 16540206
AN - SCOPUS:33746705116
VL - 41
SP - 675
EP - 682
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
IS - 5
ER -