title: Structure-based de novo design and synthesis of aminothiazole-based p38 MAP kinase inhibitors.
abstract: p38 mitogen-activated protein kinase (MAPK) is a promising target for the development of therapeutics for various immunological diseases. We designed and synthesized aminothiazole-based p38 MAPK inhibitors of with IC50 values ranging from 0.1 to 2 μM by means of the structure-based de novo design of phenyl-(2-phenylamino-thiazol-5-yl)-methanone scaffold. Because these newly identified inhibitors were also screened for having desirable physicochemical properties as a drug candidate, they deserve consideration for further investigation as anti-inflammatory drugs. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of p38 MAPK are discussed in detail.
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Republic of Korea. Electronic address: hspark@sejong.ac.kr.
authors.forename: Hwangseo
authors.initials: H
authors.lastname: Park
authors.affiliation: Center for Catalytic Hydrocarbon Functionalization, Institute for Basic Science (IBS) & Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Center for Catalytic Hydrocarbon Functionalization, Institute for Basic Science (IBS) & Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea. Electronic address: hongorg@kaist.ac.kr.
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Hong
mesh_terms: D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D013844:Thiazoles; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Anti-inflammatory drugs; De novo design; Inhibitor; Kinase; p38 MAPK