Identification of Optically Active Pyrimidine Derivatives as Selective 5-HT2C Modulators
A series of pyrimidine derivatives 4a–i were synthesized and evaluated for their binding affinities towards 5-HT2C receptors. With regard to designed molecules 4a–i, the influence of the size of alkyl ether and the absolute configuration of a stereogenic center on the 5-HT2C binding affinity and sel...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2017-08-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/22/9/1416 |
| _version_ | 1818541847469883392 |
|---|---|
| author | Juhyeon Kim Hanbyeol Jo Hyunseung Lee Hyunah Choo Hak Joong Kim Ae Nim Pae Yong Seo Cho Sun-Joon Min |
| author_facet | Juhyeon Kim Hanbyeol Jo Hyunseung Lee Hyunah Choo Hak Joong Kim Ae Nim Pae Yong Seo Cho Sun-Joon Min |
| author_sort | Juhyeon Kim |
| collection | DOAJ |
| description | A series of pyrimidine derivatives 4a–i were synthesized and evaluated for their binding affinities towards 5-HT2C receptors. With regard to designed molecules 4a–i, the influence of the size of alkyl ether and the absolute configuration of a stereogenic center on the 5-HT2C binding affinity and selectivity was studied. The most promising diasteromeric mixtures 4d and 4e were selected in the initial radioligand binding assay and they were further synthesized as optically active forms starting from optically active alcohols 5d and 5e, prepared by an enzymatic kinetic resolution. Pyrimidine analogue (R,R)-4e displayed an excellent 5-HT2C binding affinity with good selectivity values against a broad range of other 5-HT receptor subtypes. |
| first_indexed | 2024-12-11T22:14:31Z |
| format | Article |
| id | doaj.art-61a418fa2f6449e19d0f7ba443c22919 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T22:14:31Z |
| publishDate | 2017-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-61a418fa2f6449e19d0f7ba443c229192022-12-22T00:48:38ZengMDPI AGMolecules1420-30492017-08-01229141610.3390/molecules22091416molecules22091416Identification of Optically Active Pyrimidine Derivatives as Selective 5-HT2C ModulatorsJuhyeon Kim0Hanbyeol Jo1Hyunseung Lee2Hyunah Choo3Hak Joong Kim4Ae Nim Pae5Yong Seo Cho6Sun-Joon Min7Center for Neuro-Medicine, Korea Institute of Science and Technology (KIST), 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, KoreaDepartment of Chemical & Molecular Engineering/Applied Chemistry, Hanyang University, Ansan, Gyeonggi-do 15588, KoreaDepartment of Chemical & Molecular Engineering/Applied Chemistry, Hanyang University, Ansan, Gyeonggi-do 15588, KoreaCenter for Neuro-Medicine, Korea Institute of Science and Technology (KIST), 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, KoreaDepartment of Chemistry, Korea University, Seoul 02841, KoreaDepartment of Biological Chemistry, Korea University of Science and Technology (UST), 217 Gajungro, Yuseong-gu, Daejeon 34113, KoreaCenter for Neuro-Medicine, Korea Institute of Science and Technology (KIST), 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, KoreaDepartment of Chemical & Molecular Engineering/Applied Chemistry, Hanyang University, Ansan, Gyeonggi-do 15588, KoreaA series of pyrimidine derivatives 4a–i were synthesized and evaluated for their binding affinities towards 5-HT2C receptors. With regard to designed molecules 4a–i, the influence of the size of alkyl ether and the absolute configuration of a stereogenic center on the 5-HT2C binding affinity and selectivity was studied. The most promising diasteromeric mixtures 4d and 4e were selected in the initial radioligand binding assay and they were further synthesized as optically active forms starting from optically active alcohols 5d and 5e, prepared by an enzymatic kinetic resolution. Pyrimidine analogue (R,R)-4e displayed an excellent 5-HT2C binding affinity with good selectivity values against a broad range of other 5-HT receptor subtypes.https://www.mdpi.com/1420-3049/22/9/1416pyrimidineoptically activeenzymatic kinetic resolution5-HT2C receptorbinding affinityselectivity |
| spellingShingle | Juhyeon Kim Hanbyeol Jo Hyunseung Lee Hyunah Choo Hak Joong Kim Ae Nim Pae Yong Seo Cho Sun-Joon Min Identification of Optically Active Pyrimidine Derivatives as Selective 5-HT2C Modulators Molecules pyrimidine optically active enzymatic kinetic resolution 5-HT2C receptor binding affinity selectivity |
| title | Identification of Optically Active Pyrimidine Derivatives as Selective 5-HT2C Modulators |
| title_full | Identification of Optically Active Pyrimidine Derivatives as Selective 5-HT2C Modulators |
| title_fullStr | Identification of Optically Active Pyrimidine Derivatives as Selective 5-HT2C Modulators |
| title_full_unstemmed | Identification of Optically Active Pyrimidine Derivatives as Selective 5-HT2C Modulators |
| title_short | Identification of Optically Active Pyrimidine Derivatives as Selective 5-HT2C Modulators |
| title_sort | identification of optically active pyrimidine derivatives as selective 5 ht2c modulators |
| topic | pyrimidine optically active enzymatic kinetic resolution 5-HT2C receptor binding affinity selectivity |
| url | https://www.mdpi.com/1420-3049/22/9/1416 |
| work_keys_str_mv | AT juhyeonkim identificationofopticallyactivepyrimidinederivativesasselective5ht2cmodulators AT hanbyeoljo identificationofopticallyactivepyrimidinederivativesasselective5ht2cmodulators AT hyunseunglee identificationofopticallyactivepyrimidinederivativesasselective5ht2cmodulators AT hyunahchoo identificationofopticallyactivepyrimidinederivativesasselective5ht2cmodulators AT hakjoongkim identificationofopticallyactivepyrimidinederivativesasselective5ht2cmodulators AT aenimpae identificationofopticallyactivepyrimidinederivativesasselective5ht2cmodulators AT yongseocho identificationofopticallyactivepyrimidinederivativesasselective5ht2cmodulators AT sunjoonmin identificationofopticallyactivepyrimidinederivativesasselective5ht2cmodulators |