Isothiazoles. Part XV. A mild and efficient synthesis of new antiproliferative 5-sulfanylsubstituted 3-alkylaminoisothiazole 1,1-dioxides.
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.
Istituto di Chimica Organica A. Marchesini, Facoltà di Farmacia, Università di Milano, via Venezian 21, 20133 Milano, Italy. francesca.clerici@unimi.it
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Clerici
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Contini
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Corsini
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Ferri
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Grzesiak
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Pellegrino
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Sala
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Yokoyama
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000478:Alkylation; D000586:Amination; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D010100:Oxygen / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000737:chemistry*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013844:Thiazoles; D013455:Sulfur; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D010100:Oxygen