Iwona E Głowacka, Dorota G Piotrowska, Graciela Andrei, Dominique Schols, Robert Snoeck, Andrzej E Wróblewski
{"title":"含酰胺键的无环核苷膦酸盐;羟基衍生物。","authors":"Iwona E Głowacka, Dorota G Piotrowska, Graciela Andrei, Dominique Schols, Robert Snoeck, Andrzej E Wróblewski","doi":"10.1007/s00706-019-2351-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>To study the influence of a linker rigidity and changes in donor-acceptor properties, three series of nucleotide analogs containing a P-X-HN-C(O)- residue (X=CH(OH)CH<sub>2</sub>, CH(OH)CH<sub>2</sub>CH<sub>2</sub>, CH<sub>2</sub>CH(OH)CH<sub>2</sub>) as a replacement for the P-CH<sub>2</sub>-O-CHR- fragment in acyclic nucleoside phosphonates, e.g., adefovir, cidofovir, were synthesized. EDC proved to provide good yields of the analogs from the respective ω-amino-1- or -2-hydroxyalkylphosphonates and nucleobase-derived acetic acids. New phosphorus-nucleobase linkers are characterized by two fragments of the restricted rotation within amide bonds and in four-atom units (P-CH(OH)-CH<sub>2</sub>-N, P-CH(OH)-CH<sub>2</sub>-C and P-CH<sub>2</sub>-CH(OH)-C) in which antiperiplanar disposition of P and N/C atoms was deduced from <sup>1</sup>H and <sup>13</sup>C NMR spectral data. The synthesized analogs P-X-HNC(O)-CH<sub>2</sub>B [X=CH(OH)CH<sub>2</sub>, CH(OH)CH<sub>2</sub>CH<sub>2</sub>, CH<sub>2</sub>CH(OH)CH<sub>2</sub>] appeared inactive in antiviral assays on a wide variety of DNA and RNA viruses at concentrations up to 100 μM, while two phosphonates showed cytostatic activity towards myeloid leukemia (K-562) and multiple myeloma cells (MM.1S) with IC<sub>50</sub> of 28.8 and 40.7 μM, respectively.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":18766,"journal":{"name":"Monatshefte Fur Chemie","volume":"150 4","pages":"733-745"},"PeriodicalIF":1.7000,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s00706-019-2351-y","citationCount":"1","resultStr":"{\"title\":\"Acyclic nucleoside phosphonates containing the amide bond: hydroxy derivatives.\",\"authors\":\"Iwona E Głowacka, Dorota G Piotrowska, Graciela Andrei, Dominique Schols, Robert Snoeck, Andrzej E Wróblewski\",\"doi\":\"10.1007/s00706-019-2351-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Abstract: </strong>To study the influence of a linker rigidity and changes in donor-acceptor properties, three series of nucleotide analogs containing a P-X-HN-C(O)- residue (X=CH(OH)CH<sub>2</sub>, CH(OH)CH<sub>2</sub>CH<sub>2</sub>, CH<sub>2</sub>CH(OH)CH<sub>2</sub>) as a replacement for the P-CH<sub>2</sub>-O-CHR- fragment in acyclic nucleoside phosphonates, e.g., adefovir, cidofovir, were synthesized. EDC proved to provide good yields of the analogs from the respective ω-amino-1- or -2-hydroxyalkylphosphonates and nucleobase-derived acetic acids. New phosphorus-nucleobase linkers are characterized by two fragments of the restricted rotation within amide bonds and in four-atom units (P-CH(OH)-CH<sub>2</sub>-N, P-CH(OH)-CH<sub>2</sub>-C and P-CH<sub>2</sub>-CH(OH)-C) in which antiperiplanar disposition of P and N/C atoms was deduced from <sup>1</sup>H and <sup>13</sup>C NMR spectral data. The synthesized analogs P-X-HNC(O)-CH<sub>2</sub>B [X=CH(OH)CH<sub>2</sub>, CH(OH)CH<sub>2</sub>CH<sub>2</sub>, CH<sub>2</sub>CH(OH)CH<sub>2</sub>] appeared inactive in antiviral assays on a wide variety of DNA and RNA viruses at concentrations up to 100 μM, while two phosphonates showed cytostatic activity towards myeloid leukemia (K-562) and multiple myeloma cells (MM.1S) with IC<sub>50</sub> of 28.8 and 40.7 μM, respectively.</p><p><strong>Graphical abstract: </strong></p>\",\"PeriodicalId\":18766,\"journal\":{\"name\":\"Monatshefte Fur Chemie\",\"volume\":\"150 4\",\"pages\":\"733-745\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2019-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1007/s00706-019-2351-y\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Monatshefte Fur Chemie\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1007/s00706-019-2351-y\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2019/3/1 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Monatshefte Fur Chemie","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s00706-019-2351-y","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2019/3/1 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Acyclic nucleoside phosphonates containing the amide bond: hydroxy derivatives.
Abstract: To study the influence of a linker rigidity and changes in donor-acceptor properties, three series of nucleotide analogs containing a P-X-HN-C(O)- residue (X=CH(OH)CH2, CH(OH)CH2CH2, CH2CH(OH)CH2) as a replacement for the P-CH2-O-CHR- fragment in acyclic nucleoside phosphonates, e.g., adefovir, cidofovir, were synthesized. EDC proved to provide good yields of the analogs from the respective ω-amino-1- or -2-hydroxyalkylphosphonates and nucleobase-derived acetic acids. New phosphorus-nucleobase linkers are characterized by two fragments of the restricted rotation within amide bonds and in four-atom units (P-CH(OH)-CH2-N, P-CH(OH)-CH2-C and P-CH2-CH(OH)-C) in which antiperiplanar disposition of P and N/C atoms was deduced from 1H and 13C NMR spectral data. The synthesized analogs P-X-HNC(O)-CH2B [X=CH(OH)CH2, CH(OH)CH2CH2, CH2CH(OH)CH2] appeared inactive in antiviral assays on a wide variety of DNA and RNA viruses at concentrations up to 100 μM, while two phosphonates showed cytostatic activity towards myeloid leukemia (K-562) and multiple myeloma cells (MM.1S) with IC50 of 28.8 and 40.7 μM, respectively.
期刊介绍：
"Monatshefte für Chemie/Chemical Monthly" was originally conceived as an Austrian journal of chemistry. It has evolved into an international journal covering all branches of chemistry. Featuring the most recent advances in research in analytical chemistry, biochemistry, inorganic, medicinal, organic, physical, structural, and theoretical chemistry, Chemical Monthly publishes refereed original papers and a section entitled "Short Communications". Reviews, symposia in print, and issues devoted to special fields will also be considered.
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