title: 6-Phenoxy-2-phenylbenzoxazoles, novel inhibitors of receptor for advanced glycation end products (RAGE).
abstract: Receptor for advanced glycation end products (RAGE) is known to be involved in the transportation of amyloid β (Aβ) peptides and causes the accumulation of Aβ in the brain. Moreover, recent studies suggest that the interactions between RAGE and Aβ peptides may be the culprit behind Alzheimer's disease (AD). Inhibitors of the RAGE-Aβ interactions would not only prevent the accumulation of toxic Aβ in the brain, and but also block the progress of AD, therefore, have the potential to provide a 'disease-modifying therapy'. In this study, we have developed a series of 6-phenoxy-2-phenylbenzoxazole analogs as novel inhibitors of RAGE. Among these derivatives, we found several effective inhibitors that block the RAGE-Aβ interactions without causing significant cellular toxicity. Further testing showed that compound 48 suppressed Aβ induced toxicity in mouse hippocampal neuronal cells and reduced Aβ levels in the brains of a transgenic mouse model of AD after oral administration.
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea; Medifron DBT, Sandanro 349, Danwon-Gu, Ansan-City, Gyeonggi-Do 425-839, South Korea.
authors.forename: Kwanghyun
authors.initials: K
authors.lastname: Choi
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Kwang Su
authors.initials: KS
authors.lastname: Lim
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Juhee
authors.initials: J
authors.lastname: Shin
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Seo Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Young-Ger
authors.initials: YG
authors.lastname: Suh
authors.affiliation: Medifron DBT, Sandanro 349, Danwon-Gu, Ansan-City, Gyeonggi-Do 425-839, South Korea.
authors.forename: Hyun-Seok
authors.initials: HS
authors.lastname: Hong
authors.affiliation: Medifron DBT, Sandanro 349, Danwon-Gu, Ansan-City, Gyeonggi-Do 425-839, South Korea.
authors.forename: Hee
authors.initials: H
authors.lastname: Kim
authors.affiliation: Medifron DBT, Sandanro 349, Danwon-Gu, Ansan-City, Gyeonggi-Do 425-839, South Korea.
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Ha
authors.affiliation: Medifron DBT, Sandanro 349, Danwon-Gu, Ansan-City, Gyeonggi-Do 425-839, South Korea.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Global Medical Science, Sungshin University, Seoul 142-732, South Korea.
authors.forename: Jiyoun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea. Electronic address: jeewoo@snu.ac.kr.
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
mesh_terms: D016229:Amyloid beta-Peptides / Q000032:analysis / Q000633:toxicity; D000818:Animals; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D001583:Benzoxazoles; D000067759:Receptor for Advanced Glycation End Products
keywords: Alzheimer’s disease; Amyloid β; Receptor for advanced glycation end products, RAGE