title: Design and synthesis of subtype-selective cyclooxygenase (COX) inhibitors derived from thalidomide.
abstract: A series of substituted indoline and indole derivatives with cyclooxygenase (COX)-inhibitory activity was prepared during our structural development studies based on thalidomide as a multi-template lead compound. Structure-activity relationship studies indicated that the nature of the substituent introduced at the benzene ring of the indoline (indole) backbone, and the length and type of the linking group between the nitrogen atom of indoline (indole) and the N-substituent are important for the activity. This study has led to the identification of COX-1-selective inhibitors, and these should be useful not only as pharmacological tools to investigate the physiology and pathophysiology of COX, but also as sophisticated leads for the development of novel drugs to treat COX-associated diseases, such as inflammatory diseases, and cancer.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sano
authors.forename: Tomomi
authors.initials: T
authors.lastname: Noguchi
authors.forename: Aya
authors.initials: A
authors.lastname: Tanatani
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyachi
mesh_terms: D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D015394:Molecular Structure; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D013329:Structure-Activity Relationship; D013792:Thalidomide / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D013792:Thalidomide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases