title: Indole inhibitors of human nonpancreatic secretory phospholipase A2. 3. Indole-3-glyoxamides.
abstract: The preceding papers of this series detail the development of functionalized indole-3-acetamides as inhibitors of hnps-PLA2. We describe here the extension of the structure-activity relationship to include a series of indole-3-glyoxamide derivatives. Functionalized indole-3-glyoxamides with an acidic substituent appended to the 4- or 5-position of the indole ring were prepared and tested as inhibitors of hnps-PLA2. It was found that the indole-3-glyoxamides with a 4-oxyacetic acid substituent had optimal inhibitory activity. These inhibitors exhibited an improvement in potency over the best of the indole-3-acetamides, and LY315920 (6m) was selected for evaluation clinically as an hnps-PLA2 inhibitor.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Draheim
authors.forename: N J
authors.initials: NJ
authors.lastname: Bach
authors.forename: R D
authors.initials: RD
authors.lastname: Dillard
authors.forename: D R
authors.initials: DR
authors.lastname: Berry
authors.forename: D G
authors.initials: DG
authors.lastname: Carlson
authors.forename: N Y
authors.initials: NY
authors.lastname: Chirgadze
authors.forename: D K
authors.initials: DK
authors.lastname: Clawson
authors.forename: L W
authors.initials: LW
authors.lastname: Hartley
authors.forename: L M
authors.initials: LM
authors.lastname: Johnson
authors.forename: N D
authors.initials: ND
authors.lastname: Jones
authors.forename: E R
authors.initials: ER
authors.lastname: McKinney
authors.forename: E D
authors.initials: ED
authors.lastname: Mihelich
authors.forename: J L
authors.initials: JL
authors.lastname: Olkowski
authors.forename: R W
authors.initials: RW
authors.lastname: Schevitz
authors.forename: A C
authors.initials: AC
authors.lastname: Smith
authors.forename: D W
authors.initials: DW
authors.lastname: Snyder
authors.forename: C D
authors.initials: CD
authors.lastname: Sommers
authors.forename: J P
authors.initials: JP
authors.lastname: Wery
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D013329:Structure-Activity Relationship; D013453:Sulfonylurea Compounds / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D013453:Sulfonylurea Compounds; C032160:glyoxamide; D010741:Phospholipases A; D054467:Phospholipases A2