S-2-(OMEGA-AMINOALKYLAMINO)ETHYL DIHYDROGEN PHOSPHOROTHIOATES AND RELATED COMPOUNDS AS POTENTIAL ANTIRADIATION AGENTS

A number of S-2-(ω-amininoalkylamino)ethyl and S-3-(ω-aminoalkylamino)propyl dihydrogen phosphorothioates (3a-e, 18a-c) and some related compounds including the S-2-(ω-amiuoalkylamino)ethyl hydrogen thiosulfates lOa-c have been prepared and evaluated for radioprotective activity in mice. Intermediate N-(2-bromoethyl)-α,ω-alkanediamine dihydrobromides (2a-e) were prepared by the Cortese treatment of the 2-(ω-amininoalkylamino)ethanols 1a-e; the potential of a Gabriel synthesis from the 3-(ω-phthalimidoalkyl)-2-oxazolidinones 7a-c was demonstrated by the conversion of N-[3-(2-bromoethylamino)propyl]phthalimide hydrobromide (8b) info 2b. The requisite N-(3-bromopropyl)-α, ω-alkanediamine dihydrobromides 17a-c were prepared from t he 3-(ω-aminoalkylamino)-l-propaiiols 16a and 16b and from the 3-(ω-phthalimidoalkyl)tetrahydro-1,3-oxazin-2-ones 14a and 14b in two steps involving selective cleavage of the tctrahvdrooxazinone ring. Intermediates obtained by the addition of 2-methyl-and 2,2-dimethylaziridine to acrylonitrile led to several branched-chain analogs (21a-d, 23a, and 23b). Aziridine-ring opening by ammonium thiosulfate was employed in the preparation of the inner Bunte salts 10a, 10b, 21b, and 21 d monohydrochlorides. The phosphorolhioates, as a series of a novel type, exhibited an exceptionally high level of radioprotective activity, whereas the thiosulfates were essentially nonproteetive. © 1969, American Chemical Society. All rights reserved.