title: Sulfonimidamide analogs of oncolytic sulfonylureas.
abstract: A series of sulfonimidamide analogs of the oncolytic diarylsulfonylureas was synthesized and evaluated for (1) in vitro cytotoxicity against CEM cells, (2) in vivo antitumor activity against subaxillary implanted 6C3HED lymphosarcoma, and (3) metabolic breakdown to the o-sulfate of p-chloroaniline. The separated enantiomers of one sulfonimidamide analog displayed very different activities in the in vivo screening model. In general, several analogs demonstrated excellent growth inhibitory activity in the 6C3HED model when dosed orally or intraperitoneally. A correlative structure-activity relationship to the oncolytic sulfonylureas was not apparent.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Toth
authors.forename: G B
authors.initials: GB
authors.lastname: Grindey
authors.forename: W J
authors.initials: WJ
authors.lastname: Ehlhardt
authors.forename: J E
authors.initials: JE
authors.lastname: Ray
authors.forename: G B
authors.initials: GB
authors.lastname: Boder
authors.forename: J R
authors.initials: JR
authors.lastname: Bewley
authors.forename: K K
authors.initials: KK
authors.lastname: Klingerman
authors.forename: S B
authors.initials: SB
authors.lastname: Gates
authors.forename: S M
authors.initials: SM
authors.lastname: Rinzel
authors.forename: R M
authors.initials: RM
authors.lastname: Schultz
authors.forename: L C
authors.initials: LC
authors.lastname: Weir
authors.forename: J F
authors.initials: JF
authors.lastname: Worzalla
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008809:Mice, Inbred C3H; D015394:Molecular Structure; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D012513:Sarcoma, Experimental / Q000188:drug therapy; D013453:Sulfonylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D013453:Sulfonylurea Compounds; C062821:LY 181984; C058179:sulofenur