title: Selenophene-containing inhibitors of type IIA bacterial topoisomerases.
abstract: We investigated compounds related to the previously reported antistaphyloccocal agent AVE6971 in an effort to attenuate inhibition of hERG potassium channel current that has been noted for this and related antibacterial drug classes. While most modifications of the original thiophene group compromised antibacterial activity, one selenophene analogue displayed (i) improved activity against the primary target enzyme DNA gyrase, (ii) similar activities against a panel of MRSA clinical isolates, and (iii) reduced hERG channel inhibition.
authors: Achillion Pharmaceuticals, Inc., 300 George Street, New Haven, Connecticut 06511, United States. jwiles@achillion.com
authors: Jason A
authors: JA
authors: Wiles
authors: Avinash S
authors: AS
authors: Phadke
authors: Barton J
authors: BJ
authors: Bradbury
authors: Michael J
authors: MJ
authors: Pucci
authors: Jane A
authors: JA
authors: Thanassi
authors: Milind
authors: M
authors: Deshpande
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D027101:DNA Topoisomerase IV / Q000037:antagonists & inhibitors; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D016566:Organoselenium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C524562:AVE6971; D000900:Anti-Bacterial Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D016566:Organoselenium Compounds; D010880:Piperidines; D011804:Quinolines; D013876:Thiophenes; D059005:Topoisomerase II Inhibitors; D027101:DNA Topoisomerase IV