Synthesis and biological activity of 8a-phenyldecahydroquinolines as probes of PCP's binding conformation. A new PCP-like compound with increased in vivo potency.
The synthesis and chemical resolution of cis- and trans-fused 8a-phenyldecahydroquinolines 3 and 4 are described together with the affinity of the four optically pure compounds for the PCP recognition site of the NMDA receptor complex. These compounds were also evaluated for their antagonistic effects on cGMP levels in male Swiss Webster mice, and (-)-4 was found to exhibit in vivo potency comparable to that of MK-801. The results of the binding studies are interpreted in terms of a preferred orientation of PCP's N-H bond in binding to its NMDA receptor-associated recognition site.
Chen
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Neurochemistry Research and Neuropharmacology Research, Mayo Clinic Jacksonville, Florida 32224.
Kozikowski
A P
AP
Wood
P L
PL
Reynolds
I J
IJ
Ball
R G
RG
Pang
Y P
YP
D000818:Animals; D001921:Brain / Q000378:metabolism; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D010622:Phencyclidine / Q000378:metabolism*; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D011804:Quinolines; D016194:Receptors, N-Methyl-D-Aspartate; C074388:8a-phenyldecahydroquinoline; D016291:Dizocilpine Maleate; D006152:Cyclic GMP; D010622:Phencyclidine