Yeon, Seul Ki Choi, Ji Won Park, Jong-Hyun Lee, Ye Rim Kim, Hyeon Jeong Shin, Su Jeong Jang, Bo Ko Kim, Siwon Bahn, Yong-Sun Han, Gyoonhee Lee, Yong Sup Pae, Ae Nim Park, Ki Duk 2024-01-19T23:33:28Z 2024-01-19T23:33:28Z 2021-09-03 2018-01-01 0968-0896 https://pubs.kist.re.kr/handle/201004/121823 Benzyloxyphenyl moiety is a common structure of highly potent, selective and reversible inhibitors of monoamine oxidase B (MAO-B), safinamide and sembragiline. We synthesized 4-(benzyloxy) phenyl and biphenyl-4-yl derivatives including halogen substituents on the terminal aryl unit. In addition, we modified the carbon linker between amine group and the biaryl linked unit. Among synthesized compounds, 12c exhibited the most potent and selective MAO-B inhibitory effect (hMAO-B IC50: 8.9 nM; > 10,000-fold selectivity over MAO-A) as a competitive inhibitor. In addition, 12c showed greater MAOB inhibitory activity and selectivity compared to well-known MAO-B inhibitors such as selegiline, safinamide and sembragiline. In the MPTP-induced mouse model of Parkinson's disease (PD), 12c significantly protected the tyrosine hydroxylase (TH)-immunopositive DAergic neurons and attenuated the PD-associated behavioral deficits. This study suggests characteristic structures as a MAO-B inhibitor that may provide a good insight for the development of therapeutic agents for PD. (C) 2017 Elsevier Ltd. All rights reserved. English PERGAMON-ELSEVIER SCIENCE LTD ANTICONVULSANT ACTIVITY ALZHEIMERS-DISEASE SAFINAMIDE SEMBRAGILINE DISCOVERY TARGETS DRUG Synthesis and evaluation of biaryl derivatives for structural characterization of selective monoamine oxidase B inhibitors toward Parkinson's disease therapy Article 10.1016/j.bmc.2017.11.036 1 BIOORGANIC & MEDICINAL CHEMISTRY, v.26, no.1, pp.232 - 244 BIOORGANIC & MEDICINAL CHEMISTRY 26 1 232 244 scie scopus 000419072500023 2-s2.0-85036511160 Biochemistry & Molecular Biology Chemistry, Medicinal Chemistry, Organic Biochemistry & Molecular Biology Pharmacology & Pharmacy Chemistry Article ANTICONVULSANT ACTIVITY ALZHEIMERS-DISEASE SAFINAMIDE SEMBRAGILINE DISCOVERY TARGETS DRUG Benzyloxyphenyl derivatives MAO-B inhibitor MPTP mouse model Parkinson&apos s disease