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Chemical Papers

, Volume 73, Issue 5, pp 1263–1277 | Cite as

Synthesis of novel trans-4-(phthalimidomethyl)- and 4-(imidazol-1-ylmethyl)-3-indolyl-tetrahydroisoquinolinones as possible aromatase inhibitors

  • Nikola T. BurdzhievEmail author
  • Todor I. Baramov
  • Elena R. Stanoeva
  • Stanislav G. Yanev
  • Tsveta D. Stoyanova
  • Diana H. Dimitrova
  • Kristina A. Kostadinova
Original Paper
  • 66 Downloads

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 

Notes

Acknowledgements

The authors are grateful to the FP7 project BeyondEverest. The financial support of National Science Fund of Bulgaria at the Ministry of Education and Science (project TK-X-1706/07 and UNION project DO-02-82/2008) and Sofia University “St. Kliment Ohridski” (project 80-10-190/26.04.2018) is acknowledged.

Compliance with ethical standards

Conflict of interests

The authors declare no conflict of interests.

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Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2019

Authors and Affiliations

  • Nikola T. Burdzhiev
    • 1
    Email author
  • Todor I. Baramov
    • 1
  • Elena R. Stanoeva
    • 1
  • Stanislav G. Yanev
    • 2
  • Tsveta D. Stoyanova
    • 2
  • Diana H. Dimitrova
    • 1
  • Kristina A. Kostadinova
    • 1
  1. 1.Sofia University “St. Kliment Ohridski”, Faculty of Chemistry and PharmacySofiaBulgaria
  2. 2.Department of Drug Toxicology, Institute of NeurobiologyBulgarian Academy of SciencesSofiaBulgaria

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