Hydroxy derivates of S-2-(3-aminopropylamino)ethyl dihydrogen phosphorothioate and related compounds as antiradiation agents.
The high antiradiation activity and low toxicity of sodium 3-amino-2-hydroxypropyl hydrogen phosphorothioate (1) suggested the introduction of hydroxyl groups into other types of radioprotective phosphorothioates. A number of such compounds were synthesized, including S-3-(3-aminopropylamino)-2-hydroxypropyl dihydrogen phosphorothioate (11, n equals 3), S-2-(3-amino-2-hydroxypropylamino)ethyl dihydrogen phosphorothioate (20) and its propyl homolog 26, N,N'-(2-hydroxytrimethylene)bis(S-2-aminoethyl dihydrogen phosphorothioate) (40), S-2-[3-(2-hydroxyethylamino)propylaminoi1ethyl dihydrogen phosphorothioate (44), and sodium S-2-amino-2-(hydroxymethyl)-3-hydroxypropyl hydrogen phosphorothioate (49). Compounds 11 (n equals 3), 20, 26, and 49 were highly protective when administered intraperitoneally but were generally ineffective when given perorally, as were the other hydroxylated phosphorothioates prepared. The introduction of hydroxyl groups significantly enhanced the radioprotective properties of nonhydroxylated parent compounds, however, only in the case of intraperitoneally administered.
D000284:Administration, Oral; D000818:Animals; D002588:Cesium Radioisotopes; D003037:Cobalt Radioisotopes; D003959:Diamines / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D005720:Gamma Rays; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D051379:Mice; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D011412:Propanolamines / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D011830:Radiation Effects; D011837:Radiation-Protective Agents / Q000138:chemical synthesis* / Q000633:toxicity
D002588:Cesium Radioisotopes; D003037:Cobalt Radioisotopes; D003959:Diamines; D009946:Organothiophosphorus Compounds; D011412:Propanolamines; D011837:Radiation-Protective Agents