{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:09Z","timestamp":1787029029427,"version":"build-2736575974"},"reference-count":22,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2009,10,19]],"date-time":"2009-10-19T00:00:00Z","timestamp":1255910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A series of novel 2-phenylaminopyrimidine (PAP) derivatives structurally related to STI-571 were designed and synthesized. The abilities of these compounds to inhibit proliferation were tested in human chronic myeloid leukemia K562 cells. (E)-3-(2-bromophenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide(12d) was the most effective cell growth inhibitor and was 3-fold more potent than STI-571.<\/jats:p>","DOI":"10.3390\/molecules14104166","type":"journal-article","created":{"date-parts":[[2009,10,19]],"date-time":"2009-10-19T13:17:08Z","timestamp":1255958228000},"page":"4166-4179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Design and Synthesis of Novel 2-Phenylaminopyrimidine (PAP) Derivatives and Their Antiproliferative Effects in Human Chronic Myeloid Leukemia Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Sheng","family":"Chang","sequence":"first","affiliation":[{"name":"Shenyang Pharmaceutical University, Shenyang, 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Liang","family":"Yin","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University, Shenyang, 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University, Shenyang, 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Kui","family":"Jing","sequence":"additional","affiliation":[{"name":"Mount Sinai School of Medicine, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Hua","family":"Dong","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University, Shenyang, 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2009,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s002770050473","article-title":"Molecular patho-genesis of chronic myeloid leukemia: Implications for new therapeutic strategies","volume":"78","author":"Warmuth","year":"1999","journal-title":"Ann. Hematol."},{"key":"ref_2","first-page":"251","article-title":"Molecular mechanisms of Bcr-Abl-induced oncogenesis","volume":"2","author":"Gishizky","year":"1996","journal-title":"Cytokines Mol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S0002-9343(96)00061-7","article-title":"Chronic myelogenous leukemia: A review","volume":"100","author":"Cortes","year":"1996","journal-title":"Am. J. Med."},{"key":"ref_4","first-page":"1497","article-title":"A minute chromosome in human chronic granulocytic leukemia","volume":"132","author":"Nowell","year":"1960","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/243290a0","article-title":"A new consistent chromosmal abnormality in chronic myelgenous leukemia identified by quinacrine fluorescence and Giemsa staining","volume":"243","author":"Rowley","year":"1973","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1146\/annurev.immunol.22.012703.104753","article-title":"The BCR-ABL story: Bench to beside and back","volume":"22","author":"Wong","year":"2004","journal-title":"Annu. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nm0596-561","article-title":"Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells","volume":"2","author":"Druker","year":"1996","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1056\/NEJM200104053441401","article-title":"Efficacy and safety of a specific inhibitor of Bcr-Abl tyrosine kinase in chronicmyeloid leukemia","volume":"344","author":"Druker","year":"2001","journal-title":"N. Eng. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1182\/blood.V100.3.1014","article-title":"Several types of mutations of the Abl can be found in chronic meloid leukemia patients resistant to STI571, and they can pre-exist to the onset of treatment","volume":"100","author":"Philippe","year":"2002","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1038\/sj.leu.2402741","article-title":"Molecular and chromosomal mechanisms of resistance to imanitib (STI-571) therapy","volume":"11","author":"Hochhaus","year":"2002","journal-title":"Leukemia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1126\/science.1062538","article-title":"Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification","volume":"293","author":"Gorre","year":"2001","journal-title":"Science"},{"key":"ref_12","first-page":"4236","article-title":"Cystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitor PD173955 and imatinib(STI-571)","volume":"62","author":"Nagar","year":"2002","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1126\/science.289.5486.1938","article-title":"Structure Mechanism for STI-571 inhibition of Ableson Tyrosine kinase","volume":"289","author":"Schindler","year":"2000","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0960-894X(96)00601-4","article-title":"Potent and selective inhibitors of the Abl-kinase: Phenylaminopyrimidine (PAP) derivatives","volume":"7","author":"Zimmermann","year":"1997","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1016\/S0960-894X(03)00553-5","article-title":"Synthesis of pyrim- idinopyridine-triazene conjugates targeted to Abl tyrosine kinase","volume":"13","author":"Rachid","year":"2003","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5793","DOI":"10.1016\/j.bmcl.2004.09.042","article-title":"Urea derivatives of STI-571 as inhibitors of Bcr-Abl and PDGFR kinases","volume":"14","author":"Manley","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1016\/j.bmcl.2005.11.042","article-title":"Design and synthesis of 3-substituted benzamide derivatives as Bcr-Abl kinase inhibitors","volume":"16","author":"Asaki","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ccr.2005.01.020","article-title":"AMN 107: Tightening the grip of imatinib","volume":"7","author":"Walters","year":"2005","journal-title":"Cancer Cell."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bredereck, H., Effenberger, F., and Bosch, H. (1964). Ber. Dtsch. Chem. Ges., 97, 3397\u20133406.","DOI":"10.1002\/cber.19640971220"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1096\/fasebj.12.7.531","article-title":"Differential expression of the Kell blood group and CD10 antigens: Two related membrane metallopeptidases during differentiation of K562 cells by phorbol ester and hemin","volume":"12","author":"Belhacene","year":"1998","journal-title":"FASEB J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1021\/jm051197e","article-title":"MolDock: A new technique for high-accuracy molecular docking","volume":"49","author":"Thomsen","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_22","unstructured":"(2003). Sybyl Version 6.9.1, Tripos Associates."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/14\/10\/4166\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T22:11:23Z","timestamp":1760220683000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/14\/10\/4166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,10,19]]},"references-count":22,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2009,10]]}},"alternative-id":["14104166"],"URL":"https:\/\/doi.org\/10.3390\/molecules14104166","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,10,19]]}}}