1,2,4-Benzotriazine oxide derivs. - used for radio-sensitising hypoxic tumour cells and selectively killing hypoxic tumour cells

摘要

Method of radiosensitising hypoxic tumour cells comprises administering a 1,2,4-benzotriazine oide deriv. of formula (I) where X = OH, OR, NH2, NR or NR2; each R = 1-4C alkyl or morpholino and may further be substd. with OH, alkoxy, amino or halogeno; n = 0 or 1; Y1, Y2 = halogeno, hydrocarbyl (1-14C) including cyclic and unsatd. hydrocarbyl, opt. substd. with 1 or 2 substits. selected from halogeno, OH, epoxy, alkoxy, alkylthio, amino (including morpholino), acyloxy, acylamido and their thio analogues, carboxy, alkoxycarbonyl, carbamoyl or alkylcarbamyl and where the hydrocarbyl can opt. be interrupted by a single ether (-O-) linkage or Y1 and Y2 are NHR1, O(CO)R1, NH(CO)R1, O(SO)R1 or O(POR1)R1; R1 = a hydrocarbyl opt. substd. as before. Also claimed is a method of selectively killing hypoxic tumour cells comprising administering directly to the cells (I), where X = NH2, NHR or NR2 and n is 1 and R may also be amide, and Y1, Y2 may also be H. (C) Also claimed are cpds. (I) where (a) X is OH, OR or NR2 and n is 0 or 1, Y1, Y2 may also be H; (b) X is NH2 or NHR and n is 0, Y1, Y2 may also be H. (c) X is NH2, n is 1 and Y1 and Y2 are H, satd. or unsatd. hydrocarbyl or 7-14C or unsatd. hydrocarbyl of 1-6C either hydrocarbyl being unsubstd. or substd. with halogen, OH, epoxy, alkoxy, alkylthio, amino, morpholino, acyloxy, acylamido and their thio analogues and where the hydrocarbyl can be opt. interrupted by a single ether linkage or Y1 and Y2 are NHR1, O(CO)R1, NH(CO)R1, O(SO)R1 or O(POR1)R1.