Design, Synthesis, and Monoamine Oxidase B Selective Inhibitory Activity of N‑Arylated Heliamine Analogues

Monoamine oxidase B (MAO-B) metabolizes monoamines such as dopamine regarding neural transmission and controls its level in the mammalian’s brain. When MAO-B metabolizes dopamine abnormally, normal neurotransmission does not occur, and central nervous system disorders such as Parkinson’s disease may...

Full description

Saved in:

Bibliographic Details
Published in:	ACS medicinal chemistry letters Vol. 13; no. 10; pp. 1582 - 1590
Main Authors:	Yamada, Makito, Hirose, Yu, Lin, Bangzhong, Fumimoto, Megumi, Nunomura, Kazuto, Natchanun, Sirimangkalakitti, Takahashi, Naoyuki, Ohki, Yuuta, Sako, Makoto, Murai, Kenichi, Harada, Kazuo, Arai, Masayoshi, Suzuki, Sayo, Nakamura, Tomonori, Haruta, Junichi, Arisawa, Mitsuhiro
Format:	Journal Article
Language:	English
Published:	American Chemical Society 13-10-2022
Subjects:	Letter Buchwald−Hartwig amination heliamine derivatives MAO-B monoamine oxidase
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Monoamine oxidase B (MAO-B) metabolizes monoamines such as dopamine regarding neural transmission and controls its level in the mammalian’s brain. When MAO-B metabolizes dopamine abnormally, normal neurotransmission does not occur, and central nervous system disorders such as Parkinson’s disease may develop. Although several MAO inhibitors have been developed, most of them have no selectivity between monoamine oxidase A (MAO-A) and MAO-B, or they work irreversibly against the enzyme. This report describes the first case of screening of N-arylated heliamine derivatives to develop novel MAO-B selective inhibitors that can be synthesized concisely by microwave-assisted Pd nanoparticle-catalyzed Buchwald–Hartwig amination. We discovered that the derivatives 4h, 4i, and 4j display inhibitory activity against MAO-B with IC50 values of 1.55, 13.5, and 5.08 μM, respectively.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1948-5875 1948-5875
DOI:	10.1021/acsmedchemlett.2c00228