Preparative Scale Resolution of Enantiomers Enables Accelerated Drug Discovery and Development
The provision of pure enantiomers is of increasing importance not only for the pharmaceutical industry but also for agro-chemistry and biotechnology. In drug discovery and development, the enantiomers of a chiral drug depict unique chemical and pharmacological behaviors in a chiral environment, such...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-01-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/22/1/158 |
| _version_ | 1818381151206637568 |
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| author | Hanna Leek Shalini Andersson |
| author_facet | Hanna Leek Shalini Andersson |
| author_sort | Hanna Leek |
| collection | DOAJ |
| description | The provision of pure enantiomers is of increasing importance not only for the pharmaceutical industry but also for agro-chemistry and biotechnology. In drug discovery and development, the enantiomers of a chiral drug depict unique chemical and pharmacological behaviors in a chiral environment, such as the human body, in which the stereochemistry of the chiral drugs determines their pharmacokinetic, pharmacodynamic and toxicological properties. We present a number of challenging case studies of up-to-kilogram separations of racemic or enriched isomer mixtures using preparative liquid chromatography and super critical fluid chromatography to generate individual enantiomers that have enabled the development of new candidate drugs within AstraZeneca. The combination of chromatography and racemization as well as strategies on when to apply preparative chiral chromatography of enantiomers in a multi-step synthesis of a drug compound can further facilitate accelerated drug discovery and the early clinical evaluation of the drug candidates. |
| first_indexed | 2024-12-14T02:30:01Z |
| format | Article |
| id | doaj.art-74dead081ec6491f8bf30d1affc2eb0b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-14T02:30:01Z |
| publishDate | 2017-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-74dead081ec6491f8bf30d1affc2eb0b2022-12-21T23:20:17ZengMDPI AGMolecules1420-30492017-01-0122115810.3390/molecules22010158molecules22010158Preparative Scale Resolution of Enantiomers Enables Accelerated Drug Discovery and DevelopmentHanna Leek0Shalini Andersson1Respiratory, Inflammation and Autoimmunity, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, 431 83 Molndal, SwedenCardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, 431 83 Molndal, SwedenThe provision of pure enantiomers is of increasing importance not only for the pharmaceutical industry but also for agro-chemistry and biotechnology. In drug discovery and development, the enantiomers of a chiral drug depict unique chemical and pharmacological behaviors in a chiral environment, such as the human body, in which the stereochemistry of the chiral drugs determines their pharmacokinetic, pharmacodynamic and toxicological properties. We present a number of challenging case studies of up-to-kilogram separations of racemic or enriched isomer mixtures using preparative liquid chromatography and super critical fluid chromatography to generate individual enantiomers that have enabled the development of new candidate drugs within AstraZeneca. The combination of chromatography and racemization as well as strategies on when to apply preparative chiral chromatography of enantiomers in a multi-step synthesis of a drug compound can further facilitate accelerated drug discovery and the early clinical evaluation of the drug candidates.http://www.mdpi.com/1420-3049/22/1/158chiral resolutionchiral stationary phasespreparative chromatographysupercritical fluidchromatographyracemizationactive pharmaceutical ingredientdrug discoverydrug development |
| spellingShingle | Hanna Leek Shalini Andersson Preparative Scale Resolution of Enantiomers Enables Accelerated Drug Discovery and Development Molecules chiral resolution chiral stationary phases preparative chromatography supercritical fluidchromatography racemization active pharmaceutical ingredient drug discovery drug development |
| title | Preparative Scale Resolution of Enantiomers Enables Accelerated Drug Discovery and Development |
| title_full | Preparative Scale Resolution of Enantiomers Enables Accelerated Drug Discovery and Development |
| title_fullStr | Preparative Scale Resolution of Enantiomers Enables Accelerated Drug Discovery and Development |
| title_full_unstemmed | Preparative Scale Resolution of Enantiomers Enables Accelerated Drug Discovery and Development |
| title_short | Preparative Scale Resolution of Enantiomers Enables Accelerated Drug Discovery and Development |
| title_sort | preparative scale resolution of enantiomers enables accelerated drug discovery and development |
| topic | chiral resolution chiral stationary phases preparative chromatography supercritical fluidchromatography racemization active pharmaceutical ingredient drug discovery drug development |
| url | http://www.mdpi.com/1420-3049/22/1/158 |
| work_keys_str_mv | AT hannaleek preparativescaleresolutionofenantiomersenablesaccelerateddrugdiscoveryanddevelopment AT shaliniandersson preparativescaleresolutionofenantiomersenablesaccelerateddrugdiscoveryanddevelopment |