Syntheses of conformationally constricted molecules as potential NAALADase/PSMA inhibitors.
Two six-membered ring targeted analogues of PSMA inhibitors (4a and 4b) were designed on the basis of a computational analysis and synthesized. (E,Z)-Diene 10 was subjected to the nitroso Diels-Alder reaction to give the 1,4-trans six-membered ring adduct, 4a. The cis isomer 4b was derived from similar nitroso cycloaddition reactions with the corresponding (E,E)-diene and separately from cyclohexadiene. The IC(50) values of 4a and 4b in a NAALADase assay were found to be 0.9 and 0.1 microM, respectively. [reaction: see text]
Ding
Pingyu
P
Walther Cancer Research Center & Department of Chemistry & Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556, USA.
Miller
Marvin J
MJ
Chen
Yi
Y
Helquist
Paul
P
Oliver
A Jayne
AJ
Wiest
Olaf
O
D000954:Antigens, Surface; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D043425:Glutamate Carboxypeptidase II / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure
D000954:Antigens, Surface; D004791:Enzyme Inhibitors; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II