| abstract |
Novel derivatives of 5-thia- and 5-selenopyrimidinone are found to inhibit the enzyme glycinamide ribonucleotide formyl transferase (GARFT) and amino imidazole carboxamide ribonucleotide formyl transferase (AICARFT). Novel intermediates of these compounds are also disclosed. A novel method of preparing such compounds is also disclosed, as well as methods and compositions for employing the compounds as antiproliferative agents. Compounds of the present invention include a compound having the formula III: (see formula I) wherein: n represents an integer from 0 to 5; A represents sulfur or selenium; X is methylene, monocyclic carbo- or heterocyclic ring, O, S, or -NH-; Ar is phenylene or 2,5-thienyl; and R1 and R2, which can be the same or different, are hydrogen or alkyl radicals having 1 to 6 carbon atoms; or a pharmaceutically acceptable salt thereof, OR a compound of the formula X: (see formula II) wherein: A represents sulfur or selenium; Ar represents an unsubstituted phenylene or thienylene radical; R1 and R2 represent, individually, hydrogen or C1 to C6 alkyl; R3 represents hydrogen or a straight, branched or cyclic C1-C6 alkyl group, optionally carrying one or more halogen, hydroxyl or amine groups; or a pharmaceutically acceptable salt thereof. |