C - Chemistry – Metallurgy – 07 – D
Patent
C - Chemistry, Metallurgy
07
D
167/211, 260/245
C07D 253/08 (2006.01) A61K 31/53 (2006.01) A61K 31/5377 (2006.01) A61K 41/00 (2006.01) C07D 253/10 (2006.01) C07D 413/12 (2006.01)
Patent
CA 1339217
A method of using 1,2,4-benzotriazine oxides as radiosensitizers and selective cytotoxic agents is disclosed. The compounds are shown to specifically radiosensitive hypoxic tumor cells and are additionally disclosed to be useful as specific cytotoxic agents for these cells. The oxides of the present invention are of the formula: Image wherein X is H, hydrocarbyl (1-4C), OH, OR, NH2, NHR or NR2 where each R is independently an alkyl of 1-4 carbon atoms, an amide, or a morpholino moiety and may further be substituted with hydroxy, alkoxy, amino, or halogeno substituents; wherein n is 0 or 1; and Y1 and Y2 are independently either H, halogeno, hydrocarbyl (1-14C) including cyclic and unsaturated hydrocarbyl, optionally substituted with 1 or 2 substituents selected from the group consisting of halogeno, hydroxy, epoxy, alkoxy, alkylthio, amino (including morpholino), acyloxy, acylamino and their thio analogs, alkylsulfonyl, alkylphosphonyl, carboxy, alkoxycarbonyl, carbamyl or alkylcarbamyl, and wherein the hydrocarbyl can optionally be interrupted by a single ether (-0-) linkage, or wherein Y1 and Y2 are independently either NHR', O(CO)R', NH(CO)R', O(SO)R', or O(POR)R' in which R' is a hydrocarbyl optionally substituted as defined above.
593060
Brown J. Martin
Grange Edward W.
Lee William W.
Martinez Abelardo P.
Tracy Michael
Gowling Lafleur Henderson Llp
Sri International
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