Syntheses and properties of the major hydroxy metabolites in humans of blonanserin AD-5423, a novel antipsychotic agent.
Two major metabolites in humans of blonanserin, 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta-[b]pyridine (code name AD-5423), were synthesized. The first, 7-hydroxylated AD-5423, was synthesized through a four-step process starting from 4-fluorobenzoylacetonitrile (1), and the second, 8-hydroxylated AD-5423, a nine-step process also from 1. The optical resolution, structures, and receptor binding properties of the metabolites were documented.
Ochi
Takeshi
T
Pharmaceutical Research and Technology Center, Dainippon Pharmaceutical Co., Ltd, 5-51, Ebie 1-chome, Fukushima-ku, Osaka 553-0001, Japan. takeshi-ochi@dainippon-pharm.co.jp
Sakamoto
Masato
M
Minamida
Akira
A
Suzuki
Kenji
K
Ueda
Tomohiko
T
Une
Teruaki
T
Toda
Hiroshi
H
Matsumoto
Kazuya
K
Terauchi
Yoshiaki
Y
D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D044402:Receptor, Serotonin, 5-HT2A / Q000737:chemistry / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; D010879:Piperazines; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; C113776:dopamine D2L receptor; C079310:blonanserin