Design, synthesis of orally bioavailable novel anaplastic lymphoma kinase (ALK) inhibitor diphenylaminopyrimidine analogs and efficacy study on NCI-H2228 xenografts mice model

Bioorg Med Chem Lett. 2019 Jun 15;29(12):1514-1517. doi: 10.1016/j.bmcl.2019.04.012. Epub 2019 Apr 8.

Abstract

Anaplastic lymphoma kinase (ALK) is an attractive therapeutic target for the treatment of non-small cell lung cancer (NSCLC). Within our ALK drug discovery program, we identified novel deuterated 2,4-diarylamino pyrimidine compounds as potent ALK inhibitors. The compound 11 showed better in vitro activity and in vivo efficacy with good pharmacokinetic profile. In vivo efficacy of compound 11 was better than standard drug ceritinib in NCI-H2228 xenograft mice model.

Keywords: ALK; Anaplastic lymphoma kinase; Ceritinib; Deuterated drug; Inhibitor; Kinase; NSCLC; Non-small cell lung cancer.

MeSH terms

  • Anaplastic Lymphoma Kinase / drug effects*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Disease Models, Animal
  • Heterografts
  • Mice
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Anaplastic Lymphoma Kinase