1,2,4-benzotriazine oxides as radiosensitizers and selective...

Details 1,2,4-benzotriazine oxides as radiosensitizers and selective... 1,2,4-benzotriazine oxides as radiosensitizers and selective...

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 413/00 (2006.01)

Patent

CA 1338445

A method of using 1,2,4-benzotriazine oxides of the formula Image wherein X is NH2, NHR or NRR where each R is independently an alkyl of 1-4 carbon atoms or an amide, or wherein in the case of NRR the two R groups may be linked together to form a morpholino ring, and wherein R may be further substituted with OH, alkoxy, amino or halogen substituents; n is 1; and Y1 and Y2 are independently either H; halogen; hydrocarbyl (1-14C) including cyclic and unsaturated hydrocarbyl, optionally substituted with 1 or 2 substituents selected from the group consisting of halogen, hydroxy, epoxy, alkoxy, alkylthio, amino, morpholino, acyloxy, acylamido and thio analogs thereof, carboxy, alkoxycarbonyl, carbamyl, alkylcarbamyl, and wherein the hydrocarbyl can optionally be interrupted by a single ether (-O-) 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 (1-14C) which may be substituted as defined above or a pharmaceutically acceptable salt of said compound, 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.

540932

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