title: Synthesis and structure-activity relationships of tri-substituted thiazoles as RAGE antagonists for the treatment of Alzheimer's disease.
abstract: A series of thiazole derivatives were designed, and prepared to develop RAGE antagonist for the treatment of Alzheimer's disease (AD). SAR studies were performed to optimize inhibitory activity on Aβ-RAGE binding. SAR studies showed that introducing an amino group at part A was essential for inhibitory activity on Aβ-RAGE binding. Compounds selected from Aβ-RAGE binding screening displayed inhibitory activity on Aβ transport across BBB. They also showed inhibitory activity against Aβ-induced NF-κB activation. These results indicated that our derivatives had a potential as therapeutic agent for the treatment of AD.
authors.affiliation: Korea Institute of Science and Technology, 39-1 Hawolgog-dong, Sungbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Yun Suk
authors.initials: YS
authors.lastname: Lee
authors.forename: Hee
authors.initials: H
authors.lastname: Kim
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Roh
authors.forename: Hogyu
authors.initials: H
authors.lastname: Han
authors.forename: Kye Jung
authors.initials: KJ
authors.lastname: Shin
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013844:Thiazoles