New 1-heterocyclyl:methyl-3-nitro-1,2,4-triazole derivs. - are used to increase the sensitivity of tumour cells prior to radio therapy

摘要

1-Heterocyclylmethyl-3-nitro -1,2,4-triazoles of formula (I) are new. In (I) Q is a gp. of formula Q1-Q4: R1 and R2 are H, halogen, opt. substd. alkyl, alkenyl or alkynyl, or aralkyl or aryl; X is O,S or NR3; Y is CH2, CH or XCHR3; Z is O,S or NH; R3 is H, opt. substd. 1-6C alkyl, opt. substd. aralkyl or opt. mono-to trisubstd. aryl; R4 is XR3, S(O)mR3 or R3; n is 1 or 2; m is 0-2; a is 0-3; and b is 1-4. Intermediates of formula (III) are also new. An opt. prepn. of (I), includes reacting a triazole deriv. of formula (II) with halohydrocarbon of formula ECH2Q (where m=H or alkali metal; and E is Cl, Br or I). (III) are prepd. by reacting (II) with ECH2CONHNHCZR or by reacting 3-nitro-1,2,4-triazole -1-acetic acid hydrazide with R, NCZ, CZ(E)2 or ECN. USE/ADVANTAGE - (I) are radiosensitising agents for increasing the sensitivity of tumours to radiotherapy. They have relatively low toxicity, e.g. with LD50 values of 2-10 mmole/kg.