Accession Number : ADB108945

Title :   Synthesis of Potential Prophylactic Antiradiation Agents.

Descriptive Note : Annual progress rept. 1 Jul 84-30 Jun 85,

Corporate Author : SOUTHERN RESEARCH INST BIRMINGHAM AL

Personal Author(s) : Piper, James R. ; Kussner, Conrard L.

Report Date : JUL 1986

Pagination or Media Count : 51

Abstract : The goal of this investigation is to identify modifications of S-2-(3-aminopropylamino)ethyl dihydrogen phosphorothioate (WR-2721) and related radioprotective compounds that will be less toxic, longer lasting, and effective when administered orally. During this report period we explored the possible use of thallium (I) phosphorothioate in place of sodium (or lithium) phosphorothioate as a precursor to target phosphorothioates. An advantage offered by Thallium Phosphorothioate is the facile removal of the bromide coproduct (as water-insoluble Thallium Bromide) whereas removal of Sodium Bromide (or Lithium Bromide) is often troublesome. A disadvantage is that residual impurities of toxic thallium compounds would effectively make the technique unsuitable for use in preparations of compounds for in vivo testing. Our results would indicate that Tl3SPO3 could be appropriate for salvage of a synthetic effort if preferable methods have failed, but possible contamination by toxic thallium compounds must be considered. Continuing studies on carboxy-substituted analogues of known radioprotectants (such as WR-2721 or WR-44923) led to one new compound, S-3-(3-amino-3-carboxypropylamino)propyl dihydrogen phosphorothioate. The carboxy-substituted candidates have proven to be quite challenging and time consuming. Promising synthetic approaches to three classes of branched-chain phosphorothioates were pursued. Efforts to prepare S,S-dithiocarbonates related to radioprotective phosphorothioates were initiated.

Descriptors :   *PHOSPHOROTHIOATES, *RADIOPROTECTIVE AGENTS, IN VIVO ANALYSIS, BROMIDES, LITHIUM, PRECURSORS, REMOVAL, SODIUM, LITHIUM, PREVENTION, SYNTHESIS(CHEMISTRY), IMPURITIES, THALLIUM COMPOUNDS, TOXICITY, SYNTHESIS.

Subject Categories : Radiobiology
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE