title: Novel, selective indole-based ECE inhibitors: lead optimization via solid-phase and classical synthesis.
abstract: A novel class of indole-based endothelin-converting enzyme (ECE) inhibitors was identified by high throughput screening. We report systematic optimization of this compound class by means of classical and solid-phase chemistry. Optimized compounds with a bisarylamide side chain at the 2-position of the indole skeleton exhibit low-nanomolar activity on ECE.
authors.affiliation: BAYER HealthCare AG, Business Group Pharma, Research & Development, D-42096 Wuppertal, Germany. michael.brands@bayerhealthcare.com
authors.forename: Michael
authors.initials: M
authors.lastname: Brands
authors.forename: Jens-Kerim
authors.initials: JK
authors.lastname: Ergüden
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Dirk
authors.initials: D
authors.lastname: Heimbach
authors.forename: Christian
authors.initials: C
authors.lastname: Schröder
authors.forename: Stephan
authors.initials: S
authors.lastname: Siegel
authors.forename: Johannes-Peter
authors.initials: JP
authors.lastname: Stasch
authors.forename: Stefan
authors.initials: S
authors.lastname: Weigand
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical / Q000379:methods; D000072396:Endothelin-Converting Enzymes; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes