Synthesis and evaluation of the NSCLC anti-cancer activity and physical properties of 4-aryl-N-phenylpyrimidin-2-amines

Bioorg Med Chem Lett. 2017 Oct 15;27(20):4749-4754. doi: 10.1016/j.bmcl.2017.08.063. Epub 2017 Sep 1.

Abstract

Reported herein are efforts to profile 4-aryl-N-phenylpyrimidin-2-amines in terms of their anti-cancer activity towards non small-cell lung carcinoma (NSCLC) cells. We have synthesized new 4-aryl-N-phenylpyrimidin-2-amines and assessed them in terms of their cytotoxicity (A549, NCI-H187, MCF7, Vero & KB) and physicochemical properties (logD7.4 and solubility). 13f and 13c demonstrated potent anti-cancer activity in A549 cells (0.2µM), compared to 0.4μM for the NSCLC drug Doxorubicin. 13f also displayed low experimental logD7.4 (2.9) and the best solubility (∼40μM). Compounds 13b and 13d showed the best balance of A549 anti-cancer activity and selectivity. 13g showed good activity and selectivity comparable with the anti-cancer drug Doxorubicin.

Keywords: A549; Computational design; Cytotoxicity; Lipophilicity; Solubility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Amines / chemical synthesis
  • Amines / chemistry*
  • Amines / pharmacology*
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Doxorubicin / toxicity
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Pyrimidines / chemistry
  • Solubility
  • Structure-Activity Relationship
  • Sulfonamides / chemistry*

Substances

  • Amines
  • Antineoplastic Agents
  • Pyrimidines
  • Sulfonamides
  • Doxorubicin
  • pyrimidine