Efficient synthesis of fluorothiosparfosic acid analogues with potential antitumoral activity.
In this paper, we describe a short synthesis of N-(phosphonoacetyl)-L-aspartate (PALA) analogues. The mono- and difluorinated thioacetamide precursors were prepared in one step from methyl (diethoxyphosphono)di- and monofluoromethyldithioacetates 8 and 11 as starting materials. Antiproliferating properties on a L1210 strain and ATCase inhibition of these new compounds are disclosed. ThioPALA(FF) 5c showed a remarkable cytotoxic activity towards murine leukemia L1210, when used as tetraester.
Pfund
Emmanuel
E
Laboratoire de Chimie Moléculaire et Thio-organique (UMR CNRS 6507), ENSICAEN-Université de Caen, 6 Boulevard Maréchal Juin, F-14050 Caen, France.
Lequeux
Thierry
T
Masson
Serge
S
Vazeux
Michel
M
Cordi
Alex
A
Pierre
Alain
A
Serre
Valérie
V
Hervé
Guy
G
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001221:Aspartate Carbamoyltransferase / Q000037:antagonists & inhibitors; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013853:Thioacetamide / Q000138:chemical synthesis / Q000737:chemistry
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013853:Thioacetamide; D001224:Aspartic Acid; C013195:sparfosic acid; D001221:Aspartate Carbamoyltransferase; D010746:Phosphonoacetic Acid