Structure-activity relationship study of novel NR2B-selective antagonists with arylamides to avoid reactive metabolites formation

Makoto Kawai; Isao Sakurada; Asato Morita; Yuko Iwamuro; Kazuo Ando; Hirofumi Omura; Sachiko Sakakibara; Tsutomu Masuda; Hiroki Koike; Teruki Honma; Kazunari Hattori; Tadayuki Takashima; Kunihiko Mizuno; Mayumi Mizutani; Mitsuhiro Kawamura

doi:10.1016/j.bmcl.2007.08.033

Structure-activity relationship study of novel NR2B-selective antagonists with arylamides to avoid reactive metabolites formation

Bioorg Med Chem Lett. 2007 Oct 15;17(20):5537-42. doi: 10.1016/j.bmcl.2007.08.033. Epub 2007 Aug 19.

Authors

Makoto Kawai¹, Isao Sakurada, Asato Morita, Yuko Iwamuro, Kazuo Ando, Hirofumi Omura, Sachiko Sakakibara, Tsutomu Masuda, Hiroki Koike, Teruki Honma, Kazunari Hattori, Tadayuki Takashima, Kunihiko Mizuno, Mayumi Mizutani, Mitsuhiro Kawamura

Affiliation

¹ Discovery Chemistry, Pfizer Global Research & Development, Nagoya Laboratories, 5-2 Taketoyo, Aichi 470-2393, Japan. [email protected]

PMID: 17766107
DOI: 10.1016/j.bmcl.2007.08.033

Abstract

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.

MeSH terms

Amides / chemical synthesis
Amides / chemistry*
Amides / metabolism
Amides / pharmacology*
Animals
Cell Line
Glutathione / chemistry
Humans
Mice
Molecular Structure
Neurons / drug effects
Neurons / metabolism
Phenol / chemistry
Phenols / chemistry
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
Receptors, N-Methyl-D-Aspartate / metabolism*
Structure-Activity Relationship

Substances

Amides
NR2B NMDA receptor
Phenols
Receptors, N-Methyl-D-Aspartate
Phenol
Glutathione