title: Heteroaryl-linked 5-(1H-benzimidazol-1-yl)-2-thiophenecarboxamides: potent inhibitors of polo-like kinase 1 (PLK1) with improved drug-like properties.
abstract: Potent inhibitors of PLK1 with acceptable solubility, mouse iv clearance, and reduced CYP450 inhibition were identified. Drug-like properties were improved using a heteroaryl ring as a functional handle for manipulation of inhibitors' physiochemical and DMPK properties.
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC 27709, USA. tara.r.rheault@gsk.com
authors.forename: Tara R
authors.initials: TR
authors.lastname: Rheault
authors.forename: Kelly H
authors.initials: KH
authors.lastname: Donaldson
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Badiang-Alberti
authors.forename: Ronda G
authors.initials: RG
authors.lastname: Davis-Ward
authors.forename: C Webb
authors.initials: CW
authors.lastname: Andrews
authors.forename: Ramesh
authors.initials: R
authors.lastname: Bambal
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Jackson
authors.forename: Mui
authors.initials: M
authors.lastname: Cheung
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D003198:Computer Simulation; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry; D000097869:Polo-Like Kinase 1
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D013876:Thiophenes; D000097869:Polo-Like Kinase 1