S-[2-[(2'-carbamoylethyl)amino]ethyl] phosphorothioate and related compounds as potential antiradiation agents.
A reinvestigation of the radiation protection activity of S-[2-[(2'-carbamylethyl)amino]ethyl] lithium hydrogen phosphorothioate (4a) revealed that this compound possessed good (70% protection at a dose of 600 mg/kg) activity. The thione and imino bioisosteres of 4, S-[2-(2'-thiocarbamylethylamino)ethyl] lithium hydrogen phosphorothioate (13a) and S-[2-(2'-amidinoethylamino)ethyl] phosphorothioic acid (18b) showed 100% protection at doses of 300 and 150 mg/kg, respectively. The N-methyl (4b) and tert-butyl (4c) analogues of amide 4a, the N-methyl (13b) analogue of the thioamide 13a, the N-methyl (18a) analogue of amidine (18b), and the cyclic amidine S-[2-[[2'-(4,5-dihydroimidozoyl)ethyl]amino]ethyl] lithium hydrogen phosphorothioate (21) all showed 80% protection at the highest dose tested.
Carroll
F I
FI
Research Triangle Institute, Research Triangle Park, North Carolina 27709.
Gopinathan
M B
MB
Philip
A
A
D004999:Amifostine / Q000633:toxicity; D000818:Animals; D002219:Carbamates / Q000138:chemical synthesis* / Q000633:toxicity; D055598:Chemical Phenomena; D002621:Chemistry; D007928:Lethal Dose 50; D008624:Mercaptoethylamines / Q000633:toxicity; D051379:Mice; D063086:Organothiophosphates / Q000138:chemical synthesis* / Q000633:toxicity; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis*; D011837:Radiation-Protective Agents / Q000138:chemical synthesis* / Q000633:toxicity; D013329:Structure-Activity Relationship
D002219:Carbamates; D008624:Mercaptoethylamines; D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D004999:Amifostine