Novel bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines (KRCA-0008) as potent and selective ALK inhibitors for anticancer treatment

  • Bioorg Med Chem Lett. 2013 Nov 15;23(22):6192-6. doi: 10.1016/j.bmcl.2013.08.090.
Chi Hoon Park  1 ,  Hyeonjeong Choe ,  In-Young Jang ,  So Yeong Kwon ,  Muhammad Latif ,  Heung Kyoung Lee ,  Hyeon Ji Lee ,  Eun Hye Yang ,  Jeong In Yun ,  Chong Hak Chae ,  Sung Yun Cho ,  Sang Un Choi ,  Jae Du Ha ,  Heejung Jung ,  Hyoung Rae Kim ,  Pilho Kim ,  Chong Ock Lee ,  Chang-Soo Yun ,  Kwangho Lee
Affiliations
  • 1. Bio-Organic Science Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600, Republic of Korea.
PMID: 24095090 DOI: 10.1016/j.bmcl.2013.08.090
Abstract

The synthesis of bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines is described and their structure-activity-relationship to anaplastic lymphoma kinase (ALK) is presented. KRCA-0008 is selective and potent to ALK and Ack1, and displays drug-like properties without hERG liability. KRCA-0008 demonstrates in vivo efficacy comparable to Crizotinib in xenograft mice model.

Keywords
ACK1; ALK; Diaminopyrimidine; Inhibitors; Kinases; N-Acetylpiperidine; NSCLC.
Products