Structure-activity relationship study of novel NR2B-selective antagonists with arylamides to avoid reactive metabolites formation.
A novel potent NMDA-NR2B selective antagonist without the reactive metabolites formation issue was identified. Through this study, a close correlation between reactive metabolites formation and calculated HOMO energies of parent compounds was found.
Kawai
Makoto
M
Discovery Chemistry, Pfizer Global Research & Development, Nagoya Laboratories, 5-2 Taketoyo, Aichi 470-2393, Japan. makoto.kawai@pfizer.com
Sakurada
Isao
I
Morita
Asato
A
Iwamuro
Yuko
Y
Ando
Kazuo
K
Omura
Hirofumi
H
Sakakibara
Sachiko
S
Masuda
Tsutomu
T
Koike
Hiroki
H
Honma
Teruki
T
Hattori
Kazunari
K
Takashima
Tadayuki
T
Mizuno
Kunihiko
K
Mizutani
Mayumi
M
Kawamura
Mitsuhiro
M
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D019800:Phenol / Q000737:chemistry; D010636:Phenols / Q000737:chemistry; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000577:Amides; C121001:NR2B NMDA receptor; D010636:Phenols; D016194:Receptors, N-Methyl-D-Aspartate; D019800:Phenol; D005978:Glutathione