ISSN print edition: 0366-6352
ISSN electronic edition: 1336-9075
Registr. No.: MK SR 9/7
Synthesis of novel trans-4-(phthalimidomethyl)- and 4-(imidazol-1-ylmethyl)-3-indolyl-tetrahydroisoquinolinones as possible aromatase inhibitors
Nikola T. Burdzhiev, Todor I. Baramov, Elena R. Stanoeva, Stanislav G. Yanev, Tsveta D. Stoyanova, Diana H. Dimitrova, and Kristina A. Kostadinova
Sofia University “St. Kliment Ohridski”, Faculty of Chemistry and Pharmacy, Sofia, Bulgaria
Abstract: The reaction of homophthalic anhydride with 1H-indol-3-carbaldimines was used for the preparation of trans- and cis-2-alkyl-3-indolyl-1-oxotetrahydroisoquinolin-4-carboxylic acids 3a–d. The stereochemistry of the reaction was investigated by means of 1H NMR spectroscopy. The carboxylic group of trans-3a–d was transformed stereoselectively via 4-hydroxymethyltetrahydroisoquinolin-1-ones into 4-(phthalimidomethyl)-derivatives trans-6a,b and 4-(imidazolylmethyl)-derivatives trans-8b–d. Compounds trans-6a,b and 8b–d were tested for antiaromatase activity, and the preliminary results showed that the phthalimidomethylisoquinolinone trans-6b at 50 μM concentration decreased the aromatase enzyme activity with 40%.
Keywords: Tetrahydroisoquinolinones ; Imidazoles ; Phthalimides ; Mitsunobu protocol ; Homophthalic anhydride ; Antiaromatase activity
Full paper is available at www.springerlink.com.
Chemical Papers 73 (5) 1263–1277 (2019)
Sunday, February 16, 2020