A novel kind of antitumour drugs using sulfonamide as parent compound

摘要: Abstract To obtain potent antitumour agents with low toxicity, sulfonamide derivatives containing 5-flurouracil and nitrogen mustard, respectively are designed synthesised. 1-(3-(4-Acetylaminobenzenesulfonamido)-3-oxopropyl)-5-fluoropyrimidine-2,4-dione ( 4 ) was obtained by the coupling of p -acetamidobenzenesulfonamide 3-(5-fluorouracil-1-yl) propionic acid. The hydrolysis led to 1-(3-(4-aminobenzenesulfonamido)-3-oxopropyl)-5-fluoropyrimidine-2,4-dione 5 ). Treatment -acetamidobenzenesulfonyl chloride bis(2-chloroethyl) amine 4-acetylamino- N , -bis(2-chloroethyl)benzenesulfonamide 6 Subsequent in hydrochloric acid 4-amino- hydrochloride 7 Two different synthetic route were investigated synthesis 2-[ 1 -2-pyrimidyl-aminobenzenesulfonamido] ethyl 4-bis(2-chloroethyl) aminophenyl butyrate 12b Carbobenzyloxy proved be unsuitable for protection aromatic amino group sulfadiazine since pyrimidine ring also hydrogenated at last step first under deprotection condition. In another route, acetyl firstly used as protective group, then it replaced Schiff's base. reaction chlorambucil -2-pyrimidinyl-( -acetyl)aminobenzenesulfonamido] ethanol 10b afforded -benzylidene)aminobenzenesulfonamido] 11b Compound . acute toxicity activity have been mice. exhibited high a therapeutic index (TI) 47.55.