Synthesis and mechanism of action of novel pyrimidinyl pyrazole derivatives possessing antiproliferative activity
Pyrimidinyl pyrazole derivatives 1– 4, prepared as a new scaffold of an anti-tumor agent, showed antiproliferative activity against human lung cancer cell lines and inhibited tubulin polymerization. Furthermore, it was found that compound 2 bound at the colchicine site on tubulin, but the tubulin bi...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2002-11, Vol.12 (21), p.3191-3193 |
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| container_issue | 21 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 12 |
| creator | Ohki, Hitoshi Hirotani, Kenji Naito, Hiroyuki Ohsuki, Satoru Minami, Megumi Ejima, Akio Koiso, Yukiko Hashimoto, Yuichi |
| description | Pyrimidinyl pyrazole derivatives
1–
4, prepared as a new scaffold of an anti-tumor agent, showed antiproliferative activity against human lung cancer cell lines and inhibited tubulin polymerization. Furthermore, it was found that compound
2 bound at the colchicine site on tubulin, but the tubulin binding pattern was different from that of colchicine. Here, we describe the synthesis of the derivatives and the differences of the action mechanism on tubulin polymerization inhibition between compound
2 and colchicine.
Pyrimidinyl pyrazole derivative
2, a new scaffold as an antitumor agent, showed an antiproliferative activity against the
p-glycoprotein-mediated multi-drug-resistant (MDR) cell line PC-12 and inhibited tubulin polymerization. |
| doi_str_mv | 10.1016/S0960-894X(02)00568-1 |
| format | Article |
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1–
4, prepared as a new scaffold of an anti-tumor agent, showed antiproliferative activity against human lung cancer cell lines and inhibited tubulin polymerization. Furthermore, it was found that compound
2 bound at the colchicine site on tubulin, but the tubulin binding pattern was different from that of colchicine. Here, we describe the synthesis of the derivatives and the differences of the action mechanism on tubulin polymerization inhibition between compound
2 and colchicine.
Pyrimidinyl pyrazole derivative
2, a new scaffold as an antitumor agent, showed an antiproliferative activity against the
p-glycoprotein-mediated multi-drug-resistant (MDR) cell line PC-12 and inhibited tubulin polymerization.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/S0960-894X(02)00568-1</identifier><identifier>PMID: 12372531</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Antineoplastic agents ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - pharmacology ; Binding, Competitive - drug effects ; Biological and medical sciences ; Colchicine - pharmacology ; Drug Screening Assays, Antitumor ; General aspects ; Humans ; Indicators and Reagents ; Lung Neoplasms - drug therapy ; Lung Neoplasms - pathology ; Medical sciences ; Microtubules - drug effects ; Pharmacology. Drug treatments ; Protein Binding - drug effects ; Pyrazoles - chemical synthesis ; Pyrazoles - pharmacology ; Pyrimidines - chemical synthesis ; Pyrimidines - pharmacology ; Tubulin - drug effects ; Tubulin Modulators ; Tumor Cells, Cultured</subject><ispartof>Bioorganic & medicinal chemistry letters, 2002-11, Vol.12 (21), p.3191-3193</ispartof><rights>2002 Elsevier Science Ltd</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-84b93a8285029459434987b909d03fb8a89b935cfc0fba60c127bd245a6457a73</citedby><cites>FETCH-LOGICAL-c391t-84b93a8285029459434987b909d03fb8a89b935cfc0fba60c127bd245a6457a73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0960-894X(02)00568-1$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13953126$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12372531$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ohki, Hitoshi</creatorcontrib><creatorcontrib>Hirotani, Kenji</creatorcontrib><creatorcontrib>Naito, Hiroyuki</creatorcontrib><creatorcontrib>Ohsuki, Satoru</creatorcontrib><creatorcontrib>Minami, Megumi</creatorcontrib><creatorcontrib>Ejima, Akio</creatorcontrib><creatorcontrib>Koiso, Yukiko</creatorcontrib><creatorcontrib>Hashimoto, Yuichi</creatorcontrib><title>Synthesis and mechanism of action of novel pyrimidinyl pyrazole derivatives possessing antiproliferative activity</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Pyrimidinyl pyrazole derivatives
1–
4, prepared as a new scaffold of an anti-tumor agent, showed antiproliferative activity against human lung cancer cell lines and inhibited tubulin polymerization. Furthermore, it was found that compound
2 bound at the colchicine site on tubulin, but the tubulin binding pattern was different from that of colchicine. Here, we describe the synthesis of the derivatives and the differences of the action mechanism on tubulin polymerization inhibition between compound
2 and colchicine.
Pyrimidinyl pyrazole derivative
2, a new scaffold as an antitumor agent, showed an antiproliferative activity against the
p-glycoprotein-mediated multi-drug-resistant (MDR) cell line PC-12 and inhibited tubulin polymerization.</description><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Binding, Competitive - drug effects</subject><subject>Biological and medical sciences</subject><subject>Colchicine - pharmacology</subject><subject>Drug Screening Assays, Antitumor</subject><subject>General aspects</subject><subject>Humans</subject><subject>Indicators and Reagents</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - pathology</subject><subject>Medical sciences</subject><subject>Microtubules - drug effects</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Binding - drug effects</subject><subject>Pyrazoles - chemical synthesis</subject><subject>Pyrazoles - pharmacology</subject><subject>Pyrimidines - chemical synthesis</subject><subject>Pyrimidines - pharmacology</subject><subject>Tubulin - drug effects</subject><subject>Tubulin Modulators</subject><subject>Tumor Cells, Cultured</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE2L1TAUhoMoznX0JyjdKLqonnw0bVYig18w4GIU3IU0PXWOtOmdpLdQf725vRdn6SoH8pw3bx7GnnN4y4HrdzdgNJSNUT9fg3gDUOmm5A_YjiutSqmgesh2_5AL9iSl3wBcgVKP2QUXshaV5Dt2d7OG-RYTpcKFrhjR37pAaSymvnB-pikcpzAtOBT7NdJIHYV1m92facCiw0iLm2nBVOynlDAlCr9y2Ez7OA3UY9xut7SF5vUpe9S7IeGz83nJfnz6-P3qS3n97fPXqw_XpZeGz2WjWiNdI5oKhFGVUVKZpm4NmA5k3zauMRmofO-hb50Gz0XddkJVTquqdrW8ZK9OubnG3QHTbEdKHofBBZwOydaCa801ZLA6gT7m_hF7u8__dHG1HOzRtd1c26NIC8Juri3Pey_ODxzaEbv7rbPcDLw8Ay55N_TRBU_pnpMmU0Jn7v2Jw6xjIYw2ecLgsaOIfrbdRP-p8hfHPp4Z</recordid><startdate>20021104</startdate><enddate>20021104</enddate><creator>Ohki, Hitoshi</creator><creator>Hirotani, Kenji</creator><creator>Naito, Hiroyuki</creator><creator>Ohsuki, Satoru</creator><creator>Minami, Megumi</creator><creator>Ejima, Akio</creator><creator>Koiso, Yukiko</creator><creator>Hashimoto, Yuichi</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20021104</creationdate><title>Synthesis and mechanism of action of novel pyrimidinyl pyrazole derivatives possessing antiproliferative activity</title><author>Ohki, Hitoshi ; Hirotani, Kenji ; Naito, Hiroyuki ; Ohsuki, Satoru ; Minami, Megumi ; Ejima, Akio ; Koiso, Yukiko ; Hashimoto, Yuichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-84b93a8285029459434987b909d03fb8a89b935cfc0fba60c127bd245a6457a73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Binding, Competitive - drug effects</topic><topic>Biological and medical sciences</topic><topic>Colchicine - pharmacology</topic><topic>Drug Screening Assays, Antitumor</topic><topic>General aspects</topic><topic>Humans</topic><topic>Indicators and Reagents</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - pathology</topic><topic>Medical sciences</topic><topic>Microtubules - drug effects</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Binding - drug effects</topic><topic>Pyrazoles - chemical synthesis</topic><topic>Pyrazoles - pharmacology</topic><topic>Pyrimidines - chemical synthesis</topic><topic>Pyrimidines - pharmacology</topic><topic>Tubulin - drug effects</topic><topic>Tubulin Modulators</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ohki, Hitoshi</creatorcontrib><creatorcontrib>Hirotani, Kenji</creatorcontrib><creatorcontrib>Naito, Hiroyuki</creatorcontrib><creatorcontrib>Ohsuki, Satoru</creatorcontrib><creatorcontrib>Minami, Megumi</creatorcontrib><creatorcontrib>Ejima, Akio</creatorcontrib><creatorcontrib>Koiso, Yukiko</creatorcontrib><creatorcontrib>Hashimoto, Yuichi</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ohki, Hitoshi</au><au>Hirotani, Kenji</au><au>Naito, Hiroyuki</au><au>Ohsuki, Satoru</au><au>Minami, Megumi</au><au>Ejima, Akio</au><au>Koiso, Yukiko</au><au>Hashimoto, Yuichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and mechanism of action of novel pyrimidinyl pyrazole derivatives possessing antiproliferative activity</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2002-11-04</date><risdate>2002</risdate><volume>12</volume><issue>21</issue><spage>3191</spage><epage>3193</epage><pages>3191-3193</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Pyrimidinyl pyrazole derivatives
1–
4, prepared as a new scaffold of an anti-tumor agent, showed antiproliferative activity against human lung cancer cell lines and inhibited tubulin polymerization. Furthermore, it was found that compound
2 bound at the colchicine site on tubulin, but the tubulin binding pattern was different from that of colchicine. Here, we describe the synthesis of the derivatives and the differences of the action mechanism on tubulin polymerization inhibition between compound
2 and colchicine.
Pyrimidinyl pyrazole derivative
2, a new scaffold as an antitumor agent, showed an antiproliferative activity against the
p-glycoprotein-mediated multi-drug-resistant (MDR) cell line PC-12 and inhibited tubulin polymerization.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>12372531</pmid><doi>10.1016/S0960-894X(02)00568-1</doi><tpages>3</tpages></addata></record> |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Antineoplastic agents Antineoplastic Agents - chemical synthesis Antineoplastic Agents - pharmacology Binding, Competitive - drug effects Biological and medical sciences Colchicine - pharmacology Drug Screening Assays, Antitumor General aspects Humans Indicators and Reagents Lung Neoplasms - drug therapy Lung Neoplasms - pathology Medical sciences Microtubules - drug effects Pharmacology. Drug treatments Protein Binding - drug effects Pyrazoles - chemical synthesis Pyrazoles - pharmacology Pyrimidines - chemical synthesis Pyrimidines - pharmacology Tubulin - drug effects Tubulin Modulators Tumor Cells, Cultured |
| title | Synthesis and mechanism of action of novel pyrimidinyl pyrazole derivatives possessing antiproliferative activity |
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