Substituted tetrahydroisoquinolines: synthesis, characterization, antitumor activity and other biological properties

Substituted tetrahydroisoquinolines: synthesis, characterization, antitumor activity and other... This work deals with the molecular design, synthesis and biological activity of a series of tetrahydro[1,4]dioxanisoquinolines and dimethoxyisoquinoline analogues. This study describes the synthesis strategy of these potential antitumor compounds, their multi-step synthesis and their optimization. A series of tetrahydroisoquinolines was synthesized and their cytotoxicity evaluated. Some of these tetrahydroisoquinolines showed promising KRas inhibition, antiangiogenesis activity and antiosteoporosis properties. Molecular modeling studies showed that compound 12 bind in the p1 pocket of the KRas protein making interactions with the hydrophobic residues Leu56, Tyr64, Tyr71 and Thr74 and hydrogen bonds with residues Glu37 and Asp38. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Medicinal Chemistry Elsevier

Substituted tetrahydroisoquinolines: synthesis, characterization, antitumor activity and other biological properties

Substituted tetrahydroisoquinolines: synthesis, characterization, antitumor activity and other biological properties

European Journal of Medicinal Chemistry 145 (2018) 51e63 Contents lists available at ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier.com/locate/ejmech Research paper Substituted tetrahydroisoquinolines: synthesis, characterization, antitumor activity and other biological properties a a a a b A. Sergi Capilla , Richard Soucek , Laura Grau , Manel Romero , Jaime Rubio-Martínez , c a, * Daniel H. Caignard , Maria Dolors Pujol Laboratori de Química Farmaceutica (Unitat associada al CSIC), Facultat de Farmacia, Universitat de Barcelona, Spain Department of Physical Chemistry, Faculty of Chemistry, University of Barcelona and the Institut de Recerca en Química Teorica  i Computacional (IQTCUB), Barcelona, Spain Les laboratoires Servier, 1 rue Carle Hebert-92415, Courbevoie Cedex, 92200 Neuilly-sur Seine, France art i cle i nfo abstract Article history: This work deals with the molecular design, synthesis and biological activity of a series of tetrahydro[1,4] Received 1 September 2017 dioxanisoquinolines and dimethoxyisoquinoline analogues. This study describes the synthesis strategy of Received in revised form these potential antitumor compounds, their multi-step synthesis and their optimization. A series of 29 December 2017 tetrahydroisoquinolines was synthesized and their cytotoxicity evaluated. Some of these tetrahy- Accepted 30 December 2017 droisoquinolines showed promising KRas inhibition, antiangiogenesis activity and antiosteoporosis Available online 3 January 2018 properties. Molecular modeling studies showed that compound 12 bind in the p1 pocket of the KRas protein making interactions with the hydrophobic residues Leu56, Tyr64, Tyr71 and Thr74 and hydrogen Keywords: bonds with residues Glu37 and Asp38. Isoquinolines © 2018 Elsevier Masson SAS. All rights reserved. Dioxigenated compounds Antitumor KRas Molecular dynamics Allosteric sites Drug design 1. Introduction used for the treatment...
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Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier Masson SAS
ISSN
0223-5234
eISSN
1768-3254
D.O.I.
10.1016/j.ejmech.2017.12.098
Publisher site
See Article on Publisher Site

Abstract

This work deals with the molecular design, synthesis and biological activity of a series of tetrahydro[1,4]dioxanisoquinolines and dimethoxyisoquinoline analogues. This study describes the synthesis strategy of these potential antitumor compounds, their multi-step synthesis and their optimization. A series of tetrahydroisoquinolines was synthesized and their cytotoxicity evaluated. Some of these tetrahydroisoquinolines showed promising KRas inhibition, antiangiogenesis activity and antiosteoporosis properties. Molecular modeling studies showed that compound 12 bind in the p1 pocket of the KRas protein making interactions with the hydrophobic residues Leu56, Tyr64, Tyr71 and Thr74 and hydrogen bonds with residues Glu37 and Asp38.

Journal

European Journal of Medicinal ChemistryElsevier

Published: Feb 10, 2018

References

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