title: Synthesis of potential inhibitors of hypoxanthine-guaine phosphoribosyltransferase for testing as antiprotozoal agents. 2. 1-Substituted hypoxanthines.
abstract: Evidence incicating that effective in vivo inhibition of hypoxanthine-guanine phosphoribosyltransferase (HGPRT, EC 2.4.2.8) should produce antiprotozoal activity without significant toxic effects on mammalian hosts prompted syntheses of 1-substituted hypoxanthines bearing functionalized side chains whose groupings might interact with appropriate groupings of HGPRT to form covalent bonds or strong hydrophobic bonds. 3-(Fluorosulfonyl)benzoyl, 4-(fluorosulfonyl)benzoyl, 4-chlorobenzoyl, and bromacetyl derivatives of two parent amines, 1-(2-aminoethyl)-hypoxanthine and 1-(4-aminobenzyl)hypoxanthine, were synthesized for evaluation in this connection. None of these compounds extended the life span of Plasmodium berghei infected mice or showed significant in vitro inhibition of HGPRT from H.Ep.-2 cells, but 1-[2-(bromoacetamido)ethyl]hypoxanthine displayed in vivo activity against Trypanosoma rhodesiense.
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000037:antagonists & inhibitors*; D007042:Hypoxanthines / Q000138:chemical synthesis* / Q000494:pharmacology; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D014352:Trypanosomiasis / Q000188:drug therapy
chemical_list: D000981:Antiprotozoal Agents; D007042:Hypoxanthines; D007041:Hypoxanthine Phosphoribosyltransferase