title: Design, synthesis, and evaluation of 3,5-disubstituted 7-azaindoles as Trk inhibitors with anticancer and antiangiogenic activities.
abstract: Tropomyosin-related kinase A (TrkA) is considered a promising target in the development of a therapeutic treatment of cancer and pain. In this study, we designed and synthesized a series of novel 7-azaindole-based Trk kinase inhibitors through the structure-based design strategy. By varying the functional groups at the 3 and 5 positions of a 7-azaindole scaffold, we studied the structure-activity relationships (SAR) profiles and identified a series of potent Trk inhibitors. Representative derivatives showed desirable activity in cellular proliferation and apoptosis assays. Moreover, these inhibitors exhibited noteworthy antiangiogenic activity.
authors.affiliation: Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Seunghee
authors.initials: S
authors.lastname: Hong
authors.forename: Jinhee
authors.initials: J
authors.lastname: Kim
authors.forename: Ju Hyeon
authors.initials: JH
authors.lastname: Seo
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Jung
authors.forename: Soon-Sun
authors.initials: SS
authors.lastname: Hong
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Hong
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011485:Protein Binding; D020917:Receptor, trkA / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001372:Aza Compounds; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007211:Indoles; D000081082:Phosphoinositide-3 Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D020917:Receptor, trkA