Dihydrothiazine prodrugs of thiazolium agents

C - Chemistry – Metallurgy – 07 – D

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C07D 279/12 (2006.01) A61K 31/54 (2006.01) A61P 9/00 (2006.01) A61P 9/10 (2006.01) A61P 9/12 (2006.01) A61P 9/14 (2006.01)

Patent

CA 2522756

Provided are compounds of the formula (and pharmaceutically acceptable salts thereof): (formula I) wherein: R is hydrogen, methyl, hydroxymethyl or .alpha.- hydroxyethyl; Rl and R2 are independently selected from hydrogen, C1-C6alkyl, C1-C6 hydroxyalkyl, C3-C8 cycloalkyl, C1-C6 alkenyl, Cl-C6 alkynyl, amino, monoalkylamino, dialkylaminoalkyl, and pyrrolidin-1-ylalkyl; and Y is selected from the group consisting Of C1-C6 alkyl, substituted and unsubstituted aryl; with the provisos that: (a) if Y is aryl, then at least one of Rl and R2 is other than hydrogen, and (b) if R2 is hydrogen Rl is other than methyl. Also provided are pharmaceutical compositions containing the compounds, and methods for the preparation of the compounds. The compounds are useful, among other things, as prodrugs which can be converted under acidic conditions to thiazolium agents. The compounds can be administered to mammals, including humans, for treatment of various indications.

L'invention concerne des composés de formule (I) ci-après (y compris leurs sels pharmaceutiquement acceptables). Dans cette formule, R est hydrogène, méthyle, hydroxyméthyle ou ?-hydroxyéthyle; R?l¿ et R?2¿ sont indépendamment sélectionnés dans le groupe comprenant hydrogène, alkyle C¿1?-C¿6?, hydroxyalkyle C¿1?-C¿6?, cycloalkyle C¿3?-C¿8?, alcényle C¿1?-C¿6?, alkynyle C¿l?-C¿6?, amino, monoalkylamino, dialkylaminoalkyle, et pyrrolidine-1-ylalkyle; et Y est sélectionné dans le groupe comprenant alkyle C¿1?-C¿6?, aryle substitué et non substitué; à condition que: (a) si Y est aryle, au moins l'un de R?l¿ et R?2¿ est autre qu'hydrogène, et (b) si R?2¿ est hydrogène, R?l¿ est autre que méthyle. L'invention concerne également des compositions pharmaceutiques renfermant ces composés, et des procédés relatifs à l'élaboration des composés, lesquels sont utiles, entre autres, comme promédicaments susceptibles d'être convertis dans des conditions acides en agents au thiazolium. Lesdits composés peuvent être administrés aux mammifères, y compris les êtres humains, pour le traitement de diverses affections.

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