Synthesis and structure-affinity relationships of 1,3, 5-alkylsubstituted cyclohexylamines binding at NMDA receptor PCP site.
A series of 1,3,5-alkylsubstituted cyclohexylamines 2 were synthesized as ligands for the N-methyl-D-aspartate (NMDA) receptor phencyclidine (PCP) binding site. Pure diastereomers with defined configuration of amino group 2-ax and 2-eq were obtained. The optimal size of 1,3,5-substituents was determined for cyclohexylamines 2 with an equatorial amino group in the lowest energy conformation using Hansch analysis. According to the data, the lipophilic part of cyclohexylamines 2 does not discriminate between hydrophobic regions of the PCP binding site but rather recognizes this site as a whole lipophilic pocket.
Jirgensons
A
A
Latvian institute of Organic Synthesis, 21 Aizkraukles Str., LV-1006, Riga, Latvia.
Kauss
V
V
Kalvinsh
I
I
Gold
M R
MR
Danysz
W
W
Parsons
C G
CG
Quack
G
G
D000547:Amantadine / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D003514:Cyclohexylamines / Q000138:chemical synthesis* / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000737:chemistry / Q000378:metabolism; D018716:Molecular Mimicry; D010622:Phencyclidine / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013329:Structure-Activity Relationship
D003514:Cyclohexylamines; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D000547:Amantadine; D010622:Phencyclidine