Synthesis of stable isotope labeled anacetrapib, its major metabolites and [14C]anacetrapib
Cholesteryl ester transfer protein inhibitors are an important class of compounds designed to treat hypocholesterolemia and prevent cardiovascular disease. Anacetrapib (MK‐0859) is currently in phase III trials for the treatment of elevated cholesterol levels and prevention of cardiovascular disease...
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| Veröffentlicht in: | Journal of labelled compounds & radiopharmaceuticals 2013-10, Vol.56 (12), p.600-608 |
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| container_issue | 12 |
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| container_title | Journal of labelled compounds & radiopharmaceuticals |
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| creator | Kuethe, Jeffrey T. Soli, Eric D. Royster, Pernilla Quinn, Catherine A. |
| description | Cholesteryl ester transfer protein inhibitors are an important class of compounds designed to treat hypocholesterolemia and prevent cardiovascular disease. Anacetrapib (MK‐0859) is currently in phase III trials for the treatment of elevated cholesterol levels and prevention of cardiovascular disease. In order to further support the development of anacetrapib, we prepared [M + 6]MK‐0859, which was required in support of an absolute bioavailability study of the active pharmaceutical ingredient (API). Additional support included the synthesis of an internal standard [M + 13] and three stable isotope labeled metabolites, which were used to analyze clinical samples, and [14C]MK‐0859 to support drug metabolism studies.
A labeling strategy for the preparation of [M + 6], [M + 13], and [14C]anacetrapib is described. The preparation of stable isotope labelled metabolites of anacetrapib is also described. |
| doi_str_mv | 10.1002/jlcr.3073 |
| format | Article |
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A labeling strategy for the preparation of [M + 6], [M + 13], and [14C]anacetrapib is described. The preparation of stable isotope labelled metabolites of anacetrapib is also described.</description><subject>anacetrapib</subject><subject>Anticholesteremic Agents - chemical synthesis</subject><subject>Carbon Radioisotopes - chemistry</subject><subject>Cardiovascular disease</subject><subject>CETP</subject><subject>Cholesterol</subject><subject>internal standard</subject><subject>Isotope Labeling</subject><subject>Metabolites</subject><subject>MK-0859</subject><subject>Oxazolidinones - chemical synthesis</subject><subject>Radiopharmaceuticals - chemical synthesis</subject><issn>0362-4803</issn><issn>1099-1344</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10F2LEzEUBuAgiltXL_wDEvBGwdlN5mSSmculaHUpK_jVi0VCJjmDqZmmJlO0_96U1kUEr87Fec7L4SXkKWcXnLH6ch1sugCm4B6ZcdZ1FQch7pMZA1lXomVwRh7lvGas7IR4SM5qUbdNDXJGbj_uN9M3zD7TONA8mT4g9TlOcYs0mB4DOmo2xuKUzNb3r6ifMh3NOiY6YuEx-AlzIY7ecjH_-pd9TB4MJmR8cprn5POb15_mb6vl-8W7-dWystBxqDo5DKpxykhTc8uYZLbnnWsHZR20gI4JyzmgcMA4Nm2Hsh6cEeDUYLCRcE5eHHO3Kf7YYZ706LPFEMwG4y5rLmStpFCKF_r8H7qOu7Qp3xXVMN40olNFvTwqm2LOCQe9TX40aa8504fG9aFxfWi82GenxF0_oruTfyou4PIIfvqA-_8n6evl_MMpsjpe-Dzhr7sLk75rqUA1enWz0KvljfhyvQC9gt9zW5nI</recordid><startdate>201310</startdate><enddate>201310</enddate><creator>Kuethe, Jeffrey T.</creator><creator>Soli, Eric D.</creator><creator>Royster, Pernilla</creator><creator>Quinn, Catherine A.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>201310</creationdate><title>Synthesis of stable isotope labeled anacetrapib, its major metabolites and [14C]anacetrapib</title><author>Kuethe, Jeffrey T. ; Soli, Eric D. ; Royster, Pernilla ; Quinn, Catherine A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3913-96ff75d7a6a21c0060cb19d8f7cd383ed04c113e4d301e589e62fda43d7fae563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>anacetrapib</topic><topic>Anticholesteremic Agents - chemical synthesis</topic><topic>Carbon Radioisotopes - chemistry</topic><topic>Cardiovascular disease</topic><topic>CETP</topic><topic>Cholesterol</topic><topic>internal standard</topic><topic>Isotope Labeling</topic><topic>Metabolites</topic><topic>MK-0859</topic><topic>Oxazolidinones - chemical synthesis</topic><topic>Radiopharmaceuticals - chemical synthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kuethe, Jeffrey T.</creatorcontrib><creatorcontrib>Soli, Eric D.</creatorcontrib><creatorcontrib>Royster, Pernilla</creatorcontrib><creatorcontrib>Quinn, Catherine A.</creatorcontrib><collection>Istex</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>Journal of labelled compounds & radiopharmaceuticals</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kuethe, Jeffrey T.</au><au>Soli, Eric D.</au><au>Royster, Pernilla</au><au>Quinn, Catherine A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of stable isotope labeled anacetrapib, its major metabolites and [14C]anacetrapib</atitle><jtitle>Journal of labelled compounds & radiopharmaceuticals</jtitle><addtitle>J. Label Compd. Radiopharm</addtitle><date>2013-10</date><risdate>2013</risdate><volume>56</volume><issue>12</issue><spage>600</spage><epage>608</epage><pages>600-608</pages><issn>0362-4803</issn><eissn>1099-1344</eissn><coden>JLCRD4</coden><abstract>Cholesteryl ester transfer protein inhibitors are an important class of compounds designed to treat hypocholesterolemia and prevent cardiovascular disease. Anacetrapib (MK‐0859) is currently in phase III trials for the treatment of elevated cholesterol levels and prevention of cardiovascular disease. In order to further support the development of anacetrapib, we prepared [M + 6]MK‐0859, which was required in support of an absolute bioavailability study of the active pharmaceutical ingredient (API). Additional support included the synthesis of an internal standard [M + 13] and three stable isotope labeled metabolites, which were used to analyze clinical samples, and [14C]MK‐0859 to support drug metabolism studies.
A labeling strategy for the preparation of [M + 6], [M + 13], and [14C]anacetrapib is described. The preparation of stable isotope labelled metabolites of anacetrapib is also described.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>24285236</pmid><doi>10.1002/jlcr.3073</doi><tpages>9</tpages></addata></record> |
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| ispartof | Journal of labelled compounds & radiopharmaceuticals, 2013-10, Vol.56 (12), p.600-608 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | anacetrapib Anticholesteremic Agents - chemical synthesis Carbon Radioisotopes - chemistry Cardiovascular disease CETP Cholesterol internal standard Isotope Labeling Metabolites MK-0859 Oxazolidinones - chemical synthesis Radiopharmaceuticals - chemical synthesis |
| title | Synthesis of stable isotope labeled anacetrapib, its major metabolites and [14C]anacetrapib |
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