1032900-25-6 | 5-chloro-2-N-[5-methyl-4-(piperidin-4-yl)-2-(propan-2-yloxy)phenyl]-4-N-[2-(propane-2-sulfonyl)phenyl]pyrimidine-2,4-diamine

5-chloro-N<SUB>2</SUB>-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N<SUB>4</SUB>-(2-(propane-2-sulfonyl)phenyl)pyrimidine-2,4-diaminedihydrochloride 

  1032900-25-6 

[1]Patent:CN105601614,2016,A.Locationinpatent:Paragraph0105;0106;0107;0108

[2]Patent:CN106854200,2017,A.Locationinpatent:Paragraph0078;0079;0080;0081;0082;0083;0084

[3]Patent:WO2012/82972,2012,A1.Locationinpatent:Page/Pagecolumn11-12

[4]Patent:WO2016/81538,2016,A1.Locationinpatent:Paragraph00114

[5]Patent:CN104447515,2017,B.Locationinpatent:Paragraph0055-0057

[6]Patent:US2018/86706,2018,A1.Locationinpatent:Paragraph0076-0078

761440-16-8    1032900-25-6 

[1]EuropeanJournalofMedicinalChemistry,2015,vol.93,p.1-8

[2]Patent:WO2016/81538,2016,A1

[3]Patent:KR2016/147358,2016,A

1032903-63-1    1032900-25-6 

[1]EuropeanJournalofMedicinalChemistry,2015,vol.93,p.1-8

[2]Patent:KR2016/147358,2016,A

[3]Patent:US2018/57457,2018,A1

[4]Patent:CN109748885,2019,A

[5]Patent:CN109748885,2019,A

[6]Patent:JP2019/196359,2019,A

[7]Patent:US2020/39935,2020,A1

1032900-25-6   

((bis(benzyloxy)phosphoryl)oxy)methyl4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidine-1-carboxylate 

[1]EuropeanJournalofMedicinalChemistry,2015,vol.93,p.1-8

1032900-25-6   

(phosphonooxy)methyl4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidine-1-carboxylate 

[1]EuropeanJournalofMedicinalChemistry,2015,vol.93,p.1-8

Title: Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes.

Journal: Toxicology letters 20180701

Title: 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-((4-methylpiperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)phenyl)pyrimidine-2,4-diamine (WY-135), a novel ALK inhibitor, induces cell cycle arrest and apoptosis through inhibiting ALK and its downstream pathways in Karpas299 and H2228 cells.

Journal: Chemico-biological interactions 20180325

Title: Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F.

Journal: The New England journal of medicine 20160107

Title: Phase I Study of Ceritinib (LDK378) in Japanese Patients with Advanced, Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer or Other Tumors.

Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20150701

Title: The EML4-ALK oncogene: targeting an essential growth driver in human cancer.

Journal: Proceedings of the Japan Academy. Series B, Physical and biological sciences 20150509

Title: The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer.

Journal: Cancer discovery 20140601

Title: Ceritinib in ALK-rearranged non-small-cell lung cancer.

Journal: The New England journal of medicine 20140327

Title: Overcoming drug resistance in ALK-rearranged lung cancer.

Journal: The New England journal of medicine 20140327

Title: Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials.

Journal: Journal of medicinal chemistry 20130725

Title: Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK.

Journal: Proceedings of the National Academy of Sciences of the United States of America 20070102

Title: Marsilje TH, et al. Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013 Jul 25;56(14):5675-90.

Title: Chen J, et al. LDK378: a promising anaplastic lymphoma kinase (ALK) inhibitor. J Med Chem. 2013 Jul 25;56(14):5673-4.

Title: Tucker ER, et al. Immunoassays for the quantification of ALK and phosphorylated ALK support the evaluation of on-target ALK inhibitors in neuroblastoma. Mol Oncol. 2017 Aug;11(8):996-1006.

Title: Rothschild SI. Ceritinib-a second-generation ALK inhibitor overcoming resistance in ALK-rearranged non-small celllung cancer. Transl Lung Cancer Res. 2014 Dec;3(6):379-81.