Dataset Information

Design, Synthesis and SAR in 2,4,7-Trisubstituted Pyrido[3,2-d]Pyrimidine Series as Novel PI3K/mTOR Inhibitors.

ABSTRACT: This work describes the synthesis, enzymatic activities on PI3K and mTOR, in silico docking and cellular activities of various uncommon 2,4,7 trisubstituted pyrido[3,2-d]pyrimidines. The series synthesized offers a chemical diversity in C-7 whereas C-2 (3-hydroxyphenyl) and C-4 groups (morpholine) remain unchanged, in order to provide a better understanding of the molecular determinants of PI3K selectivity or dual activity on PI3K and mTOR. Some C-7 substituents were shown to improve the efficiency on kinases compared to the 2,4-di-substituted pyrimidopyrimidine derivatives used as references. Six novel derivatives possess IC50 values on PI3Kα between 3 and 10 nM. The compounds with the best efficiencies on PI3K and mTOR induced micromolar cytotoxicity on cancer cell lines possessing an overactivated PI3K pathway.

SUBMITTER: Buron F

PROVIDER: S-EPMC8434050 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Design, Synthesis and SAR in 2,4,7-Trisubstituted Pyrido[3,2-<i>d</i>]Pyrimidine Series as Novel PI3K/mTOR Inhibitors.

Buron Frédéric F Rodrigues Nuno N Saurat Thibault T Hiebel Marie Aude MA Bourg Stéphane S Bonnet Pascal P Nehmé Reine R Morin Philippe P Percina Nathalie N Corret Justine J Vallée Béatrice B le Guevel Remy R Jourdan Marie-Lise ML Bénédetti Hélène H Routier Sylvain S

Molecules (Basel, Switzerland) 20210902 17

This work describes the synthesis, enzymatic activities on PI3K and mTOR, in silico docking and cellular activities of various uncommon 2,4,7 trisubstituted pyrido[3,2-<i>d</i>]pyrimidines. The series synthesized offers a chemical diversity in C-7 whereas C-2 (3-hydroxyphenyl) and C-4 groups (morpholine) remain unchanged, in order to provide a better understanding of the molecular determinants of PI3K selectivity or dual activity on PI3K and mTOR. Some C-7 substituents were shown to improve the ...[more]

PMID: 34500781

Dataset Information

Design, Synthesis and SAR in 2,4,7-Trisubstituted Pyrido[3,2-d]Pyrimidine Series as Novel PI3K/mTOR Inhibitors.

Publications

Design, Synthesis and SAR in 2,4,7-Trisubstituted Pyrido[3,2-<i>d</i>]Pyrimidine Series as Novel PI3K/mTOR Inhibitors.

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