The design and synthesis of inhibitors of adenosine 5'-monophosphate deaminase.
Carbocylic coformycin (4) is a potent herbicide whose primary mode of action involves inhibition of adenosine 5'-monophosphate deaminase (AMPDA) following phosphorylation of the 5'-hydroxyl group in vivo. The search for more stable and accessible structures led to the synthesis of carbocyclic nebularine (8) and deaminoformycin (10). The latter compound is a good herbicide and its corresponding 5'-monophosphate 14 is a strong inhibitor of plant AMPDA (IC50 100 nM).
Lindell
S D
SD
AgrEvo UK Limited, Essex, England. stephen.lindell@agrevo.com
Moloney
B A
BA
Hewitt
B D
BD
Earnshaw
C G
CG
Dudfield
P J
PJ
Dancer
J E
JE
D000659:AMP Deaminase / Q000037:antagonists & inhibitors*; D000241:Adenosine / Q000031:analogs & derivatives / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000378:metabolism; D003070:Coformycin / Q000031:analogs & derivatives / Q000737:chemistry; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005573:Formycins / Q000737:chemistry* / Q000494:pharmacology*; D006540:Herbicides / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D010766:Phosphorylation; D011684:Purine Nucleosides / Q000737:chemistry / Q000378:metabolism; D012263:Ribonucleosides / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D005573:Formycins; D006540:Herbicides; D011684:Purine Nucleosides; D012263:Ribonucleosides; C121296:deamineformycin; D003070:Coformycin; C030034:aristeromycin; D000255:Adenosine Triphosphate; C005248:nebularine; D000659:AMP Deaminase; D000241:Adenosine