A prodrug strategy for the oral delivery of a poorly soluble HCV NS5B thumb pocket 1 polymerase inhibitor using self-emulsifying drug delivery systems (SEDDS)
A prodrug approach was developed to address the low oral bioavailability of a poorly soluble (
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2015-01, Vol.25 (2), p.210-215 |
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| container_end_page | 215 |
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| container_issue | 2 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 25 |
| creator | Beaulieu, Pierre L De Marte, Josie Garneau, Michel Luo, Laibin Stammers, Timothy Telang, Chitra Wernic, Dominik Kukolj, George Duan, Jianmin |
| description | A prodrug approach was developed to address the low oral bioavailability of a poorly soluble ( |
| doi_str_mv | 10.1016/j.bmcl.2014.11.071 |
| format | Article |
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Crystalline prodrug analog 36 (mp 161°C) showed good solubility in individual SEDDS components (up to 80mg/mL) compared to parent 2 (<3mg/mL; mp 267°C) and cross-species bioconversions which correlated with in vitro stability in liver microsomes.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2014.11.071</identifier><identifier>PMID: 25515558</identifier><language>eng</language><publisher>England</publisher><subject>Administration, Oral ; Animals ; Drug Delivery Systems - methods ; Emulsions - administration & dosage ; Emulsions - chemistry ; Emulsions - metabolism ; Hepatitis C virus ; Microsomes - drug effects ; Microsomes - metabolism ; Nucleic Acid Synthesis Inhibitors - administration & dosage ; Nucleic Acid Synthesis Inhibitors - chemistry ; Nucleic Acid Synthesis Inhibitors - metabolism ; Prodrugs - administration & dosage ; Prodrugs - chemistry ; Prodrugs - metabolism ; Rats ; Solubility ; Viral Nonstructural Proteins - antagonists & inhibitors ; Viral Nonstructural Proteins - metabolism</subject><ispartof>Bioorganic & medicinal chemistry letters, 2015-01, Vol.25 (2), p.210-215</ispartof><rights>Copyright © 2014 Elsevier Ltd. 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Crystalline prodrug analog 36 (mp 161°C) showed good solubility in individual SEDDS components (up to 80mg/mL) compared to parent 2 (<3mg/mL; mp 267°C) and cross-species bioconversions which correlated with in vitro stability in liver microsomes.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Drug Delivery Systems - methods</subject><subject>Emulsions - administration & dosage</subject><subject>Emulsions - chemistry</subject><subject>Emulsions - metabolism</subject><subject>Hepatitis C virus</subject><subject>Microsomes - drug effects</subject><subject>Microsomes - metabolism</subject><subject>Nucleic Acid Synthesis Inhibitors - administration & dosage</subject><subject>Nucleic Acid Synthesis Inhibitors - chemistry</subject><subject>Nucleic Acid Synthesis Inhibitors - metabolism</subject><subject>Prodrugs - administration & dosage</subject><subject>Prodrugs - chemistry</subject><subject>Prodrugs - metabolism</subject><subject>Rats</subject><subject>Solubility</subject><subject>Viral Nonstructural Proteins - antagonists & inhibitors</subject><subject>Viral Nonstructural Proteins - metabolism</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9u1DAQxi0EokvpC3BAPpZD0hnHdjbHsi0UqWoPS6veLCeZtFmc9dZOkPIyPCte-ufMaUbjb75v5B9jnxByBNQnm7weGpcLQJkj5lDiG7ZAqWVWSFBv2QIqDdmykncH7EOMG0hCkPI9OxBKoVJquWB_Tvku-DZM9zyOwY50P_POBz4-EPfBOt6S639TmLnvuOU774ObefRuqh3xi9Utv1qrr0k-DXV6bX7RyDE1bh4o2Ei83z70dT8myyn225RCrstomFzsu3k_-Jf9mhLnONIQ-fH6_Oxs_eUje9dZF-nouR6ym2_nP1cX2eX19x-r08uskaDHTGEpq0IBQQlgNZImEkpYEE1bKqyUrsvUUW0lNaSrum2xECRLrUVndVkcsuMn3_QZjxPF0Qx9bMg5uyU_RYNaQ1FJjfAf0nTSshJYJKl4kjbBxxioM7vQDzbMBsHsEZqN2SM0e4QG0SSEaenzs_9UD9S-rrwwK_4CKV-ZpQ</recordid><startdate>20150115</startdate><enddate>20150115</enddate><creator>Beaulieu, Pierre L</creator><creator>De Marte, Josie</creator><creator>Garneau, Michel</creator><creator>Luo, Laibin</creator><creator>Stammers, Timothy</creator><creator>Telang, Chitra</creator><creator>Wernic, Dominik</creator><creator>Kukolj, George</creator><creator>Duan, Jianmin</creator><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><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20150115</creationdate><title>A prodrug strategy for the oral delivery of a poorly soluble HCV NS5B thumb pocket 1 polymerase inhibitor using self-emulsifying drug delivery systems (SEDDS)</title><author>Beaulieu, Pierre L ; 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| subjects | Administration, Oral Animals Drug Delivery Systems - methods Emulsions - administration & dosage Emulsions - chemistry Emulsions - metabolism Hepatitis C virus Microsomes - drug effects Microsomes - metabolism Nucleic Acid Synthesis Inhibitors - administration & dosage Nucleic Acid Synthesis Inhibitors - chemistry Nucleic Acid Synthesis Inhibitors - metabolism Prodrugs - administration & dosage Prodrugs - chemistry Prodrugs - metabolism Rats Solubility Viral Nonstructural Proteins - antagonists & inhibitors Viral Nonstructural Proteins - metabolism |
| title | A prodrug strategy for the oral delivery of a poorly soluble HCV NS5B thumb pocket 1 polymerase inhibitor using self-emulsifying drug delivery systems (SEDDS) |
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