title: Pyrazole-5-carboxamides, novel inhibitors of receptor for advanced glycation end products (RAGE).
abstract: In an effort to develop novel inhibitors of receptor for advanced glycation end products (RAGE) for the treatment of Alzheimer's disease, a series of pyrazole-5-carboxamides were designed, synthesized and biologically evaluated. Analyses of the extensive structure-activity relationship (SAR) led us to identify a 4-fluorophenoxy analog (40) that exhibited improved in vitro RAGE inhibitory activity and more favorable aqueous solubility than the parent 2-aminopyrimidine, 1. Surface plasmon resonance (SPR) and molecular docking study strongly supported the RAGE inhibitory activity of pyrazole-5-carboxamides. The brain Aβ-lowering effect of 40 is also described.
authors.affiliation: College of Pharmacy, Woosuk University, Wanju 565-701, Republic of Korea.
authors.forename: Young Taek
authors.initials: YT
authors.lastname: Han
authors.affiliation: College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Kyeojin
authors.initials: K
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Gyeong-In
authors.initials: GI
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Hongchan
authors.initials: H
authors.lastname: An
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Dohyun
authors.initials: D
authors.lastname: Son
authors.affiliation: Medifron DBT, Sandanro 349, Danwon-Gu, Ansan-City, Gyeonggi-Do 425-839, Republic of Korea.
authors.forename: Hee
authors.initials: H
authors.lastname: Kim
authors.affiliation: Medifron DBT, Sandanro 349, Danwon-Gu, Ansan-City, Gyeonggi-Do 425-839, Republic of Korea.
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Ha
authors.affiliation: College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Jun-Hyeng
authors.initials: JH
authors.lastname: Son
authors.affiliation: College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Suk-Jae
authors.initials: SJ
authors.lastname: Chung
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Park
authors.affiliation: College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea. Electronic address: ygsuh@snu.ac.kr.
authors.forename: Young-Ger
authors.initials: YG
authors.lastname: Suh
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors; D001921:Brain; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010446:Peptide Fragments / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011720:Pyrazoles; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C075222:amyloid beta-protein (1-42); C000594236:pyrazole-5-carboxamide
keywords: Alzheimer's disease, RAGE inhibitor; Pyrazole-5-carboxamide; RAGE (receptor for advanced glycation end products); SAR (structure–activity relationship)