TY - JOUR
T1 - Design, Synthesis, and Monoamine Oxidase B Selective Inhibitory Activity of N-Arylated Heliamine Analogues
AU - Yamada, Makito
AU - Hirose, Yu
AU - Lin, Bangzhong
AU - Fumimoto, Megumi
AU - Nunomura, Kazuto
AU - Natchanun, Sirimangkalakitti
AU - Takahashi, Naoyuki
AU - Ohki, Yuuta
AU - Sako, Makoto
AU - Murai, Kenichi
AU - Harada, Kazuo
AU - Arai, Masayoshi
AU - Suzuki, Sayo
AU - Nakamura, Tomonori
AU - Haruta, Junichi
AU - Arisawa, Mitsuhiro
N1 - Funding Information:
This work was partially supported by a Grant-in-Aid from the JSPS KAKENHI for Precisely Designed Catalysts with Customized Scaffolding (Grant JP 15KT0063), by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from the AMED under Grant JP21am0101084 (Support Number 3296), by Fujimorii Science and Technology Foundation and Sasagawa Science Research Foundation of The Japan Science Society.
Publisher Copyright:
© 2022 American Chemical Society.
PY - 2022/10/13
Y1 - 2022/10/13
N2 - 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.
AB - 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.
KW - Buchwald-Hartwig amination
KW - MAO-B
KW - heliamine derivatives
KW - monoamine oxidase
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U2 - 10.1021/acsmedchemlett.2c00228
DO - 10.1021/acsmedchemlett.2c00228
M3 - Article
AN - SCOPUS:85137293274
SN - 1948-5875
VL - 13
SP - 1582
EP - 1590
JO - ACS Medicinal Chemistry Letters
JF - ACS Medicinal Chemistry Letters
IS - 10
ER -