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.
Debasis Das  1 ,  Jingbing Wang  2 ,  Yong Li  2 ,  Jingli Shi  2 ,  Jian Hong  3
Affiliations
  • 1. Discovery Chemistry Research, Arromax Pharmatech Co. Ltd., Sangtian Island Innovation Park, No. 1 Huayun Road, SIP, Suzhou 215123, PR China. Electronic address: [email protected].
  • 2. Discovery Chemistry Research, Arromax Pharmatech Co. Ltd., Sangtian Island Innovation Park, No. 1 Huayun Road, SIP, Suzhou 215123, PR China.
  • 3. Discovery Chemistry Research, Arromax Pharmatech Co. Ltd., Sangtian Island Innovation Park, No. 1 Huayun Road, SIP, Suzhou 215123, PR China. Electronic address: [email protected].
PMID: 31005443 DOI: 10.1016/j.bmcl.2019.04.012
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.
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