Novel, selective indole-based ECE inhibitors: lead optimization via solid-phase and classical synthesis.
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.
Brands
Michael
M
BAYER HealthCare AG, Business Group Pharma, Research & Development, D-42096 Wuppertal, Germany. michael.brands@bayerhealthcare.com
Ergüden
Jens-Kerim
JK
Hashimoto
Kentaro
K
Heimbach
Dirk
D
Schröder
Christian
C
Siegel
Stephan
S
Stasch
Johannes-Peter
JP
Weigand
Stefan
S
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
D004791:Enzyme Inhibitors; D007211:Indoles; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes