Jump to main content
Jump to site search

Issue 3, 2019
Previous Article Next Article

Conformationally restricted quinazolone derivatives as PI3Kδ-selective inhibitors: the design, synthesis and biological evaluation

Author affiliations

Abstract

A series of structurally novel quinazolone-based PI3Kδ-selective inhibitors were designed and synthesized via the approach of conformational restriction. The majority of them exhibited two-digit to single-digit nanomolar IC50 values against PI3Kδ, along with low micromolar to submicromolar GI50 values against human malignant B-cell line SU-DHL-6. The representative compound, with the most potent PI3Kδ inhibitory activity (IC50 = 6.3 nM) and anti-proliferative activity (GI50 = 0.21 μM) in this series, was further evaluated for its PI3Kδ selectivity, capability to down-regulate PI3K signaling in SU-DHL-6 cells, in vitro metabolic stability, and pharmacokinetic (PK) properties. The experimental results illustrated that this compound, as a promising lead, merits extensive structural optimization for exploring novel PI3Kδ-selective inhibitors as clinical candidates.

Graphical abstract: Conformationally restricted quinazolone derivatives as PI3Kδ-selective inhibitors: the design, synthesis and biological evaluation

Back to tab navigation

Supplementary files

Publication details

The article was received on 09 Nov 2018, accepted on 22 Jan 2019 and first published on 23 Jan 2019


Article type: Research Article
DOI: 10.1039/C8MD00556G
Citation: Med. Chem. Commun., 2019,10, 413-420

  •   Request permissions

    Conformationally restricted quinazolone derivatives as PI3Kδ-selective inhibitors: the design, synthesis and biological evaluation

    X. Ma, F. Fang, Q. Tao, L. Shen, G. Zhong, T. Qiao, X. Lv and J. Li, Med. Chem. Commun., 2019, 10, 413
    DOI: 10.1039/C8MD00556G

Search articles by author

Spotlight

Advertisements