title: Design, synthesis, and biological evaluation of pyrimidine-2-carboxamide analogs: investigation for novel RAGE inhibitors with reduced hydrophobicity and toxicity.
abstract: This paper describes an investigation of novel RAGE inhibitors with improved drug-like properties. To identify the improved drug-like RAGE inhibitor, we designed and synthesized pyrimidine-2-carboxamide analogs based on our previous work. Several potent analogs with improved hydrophilicity were identified by evaluation of RAGE inhibitory activity. In particular, one of the potent (diethylamino)ethoxymethoxy analogs did not exhibit undesired cytotoxicity in contrast with the parent RAGE inhibitors.
authors.affiliation: College of Pharmacy, CHA University, Pochen-Si, Gyeonggi-do, 487-010, Korea.
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dankook University, Cheonan, 330-714, Korea. hanyoungtaek@gmail.com.
authors.forename: Young Taek
authors.initials: YT
authors.lastname: Han
mesh_terms: D000818:Animals; D002460:Cell Line; D015195:Drug Design; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D018675:Toxicity Tests
chemical_list: D011743:Pyrimidines; D000067759:Receptor for Advanced Glycation End Products
keywords: Drug-like property; Pyrimidine-2-carboxamide; RAGE; RAGE inhibitor