2. Academic Validation
  3. Novel 2,4-diaminopyrimidines bearing fused tricyclic ring moiety for anaplastic lymphoma kinase (ALK) inhibitor

Novel 2,4-diaminopyrimidines bearing fused tricyclic ring moiety for anaplastic lymphoma kinase (ALK) inhibitor

  • Bioorg Med Chem Lett. 2017 May 15;27(10):2185-2191. doi: 10.1016/j.bmcl.2017.03.073.
Raghavendra Achary 1,  Gangadhar Rao Mathi 1,  Dong Ho Lee 2,  Chang Soo Yun 3,  Chong Ock Lee 4,  Hyoung Rae Kim 3,  Chi Hoon Park 1,  Pilho Kim 5,  Jong Yeon Hwang 6
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry and Pharmacology, University of Science & Technology, Daejeon 34113, Republic of Korea; Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
  • 2 Department of Chemistry, Sogang University, Seoul 04107, Republic of Korea; Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
  • 3 Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
  • 4 Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
  • 5 Department of Medicinal Chemistry and Pharmacology, University of Science & Technology, Daejeon 34113, Republic of Korea; Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea. Electronic address: [email protected].
  • 6 Department of Medicinal Chemistry and Pharmacology, University of Science & Technology, Daejeon 34113, Republic of Korea; Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea. Electronic address: [email protected].
PMID: 28385505 DOI: 10.1016/j.bmcl.2017.03.073
Abstract

In this study, a series of novel 2,4-diaminopyrimidines bearing fused tricyclic ring moiety was described for ALK inhibitor. The pyrazole, imidazole, 1,2,4-triazole, piperazine and phenanthridine moieties were employed at the 2-position of pyrimidine. Among the compounds synthesized, 28, 29, 36, and 42 showed promising anti-ALK activities in enzymatic- and cell-based assays. In vivo H3122 xenograft model study showed that compound 29 effectively suppressed ALK-driven tumor growth, similar to the extent of ceritinib, suggesting that it could be used for a novel ALK inhibitor development.

Keywords

2,4-Diaminopyrimidine; Anaplastic lymphoma kinase; Cancer; Fused tricyclic moiety.

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