Structural determinants for high 5-HT(2A) receptor affinity of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (SpAMDA).
The synthesis and 5-HT(2A) receptor affinities of ring altered derivatives of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (4), a structurally unique tetracyclic 5-HT(2A) receptor antagonist, are described. The characteristics of the parent compound prove to be necessary for optimal 5-HT(2A) receptor affinity. However, expansion of the size of the pyrrolidine and central rings produce compounds with reasonably high 5-HT(2A) receptor affinities. In addition, the parent compound is shown to have high 5-HT(2) receptor selectivity.
Peddi
Srinivas
S
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, PO Box 980540, Richmond, VA 23298, USA.
Roth
Bryan L
BL
Glennon
Richard A
RA
Westkaemper
Richard B
RB
D009682:Magnetic Resonance Spectroscopy; D011759:Pyrrolidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects* / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
D011759:Pyrrolidines; D044402:Receptor, Serotonin, 5-HT2A; D013141:Spiro Compounds; C494077:spiro(9,10-dihydroanthracene)-9,3'-pyrrolidine