Synthesis, in vitro binding profile, and central nervous system penetrability of the highly potent 5-HT3 receptor antagonist [3H]-4-(2-methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole.
4-(2-Methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole (5) is a highly potent member of a structurally novel series of selective serotonin-3 receptor antagonists. The synthesis of tritiated 5 and its binding profile in neuroblastoma-glioma 108-15 cells are described. Furthermore, in vivo studies in rat with this radioligand indicate that it effectively penetrates the blood-brain barrier upon peripheral administration. Thus, 5 should be a useful pharmacological tool for both in vitro and in vivo studies of this class of compounds.
Rosen
T
T
Pfizer Central Research, Department of Medicinal Chemistry, Groton, Connecticut 06340.
Seeger
T F
TF
McLean
S
S
Nagel
A A
AA
Ives
J L
JL
Guarino
K J
KJ
Bryce
D
D
Furman
J
J
Roth
R W
RW
Chalabi
P M
PM
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D005910:Glioma / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D051379:Mice; D015394:Molecular Structure; D009447:Neuroblastoma / Q000378:metabolism; D012702:Serotonin Antagonists; D013844:Thiazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
D007093:Imidazoles; D012702:Serotonin Antagonists; D013844:Thiazoles; C066281:4-(2-methoxyphenyl)-2-(4(5)-methyl-5(4)-imidazolylmethyl)thiazole