@article{https://doi.org/10.1002/cmdc.202000256,
author = {Bekker, Roberto B. W. and Fjellaksel, Richard and Hjornevik, Trine and Nuruddin, Syed and Rafique, Waqas and Hansen, Jørn H. and Sundset, Rune and Haraldsen, Ira H. and Riss, Patrick J.},
title = {Discovery of a Lead Brain-Penetrating Gonadotropin-Releasing Hormone Receptor Antagonist with Saturable Binding in Brain},
journal = {ChemMedChem},
volume = {15},
number = {17},
pages = {1624-1628},
keywords = {elagolix, fluorine-18, GnRH−R, GnRH, PET},
doi = {https://doi.org/10.1002/cmdc.202000256},
url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.202000256},
eprint = {https://chemistry-europe.onlinelibrary.wiley.com/doi/pdf/10.1002/cmdc.202000256},
abstract = {Abstract We report the synthesis, radiosynthesis and biological characterisation of two gonadotropin-releasing hormone receptor (GnRH−R) antagonists with nanomolar binding affinity. A small library of GnRH−R antagonists was synthesised in 20–67 \% overall yield with the aim of identifying a high-affinity antagonist capable of crossing the blood–brain barrier. Binding affinity to rat GnRH−R was determined by autoradiography in competitive-binding studies against [125I]buserelin, and inhibition constants were calculated by using the Cheng–Prusoff equation. The radioligands were obtained in 46–79 \% radiochemical yield and >95 \% purity and with a molar activity of 19–38 MBq/nmol by direct nucleophilic radiofluorination. Positron emission tomography imaging in rat under baseline conditions in comparison to pretreatment with a receptor-saturating dose of GnRH antagonist revealed saturable uptake (0.1 \%ID/mL) into the brain.},
year = {2020}
}

{"_id":"5FdF73AGv8HJPA3K4","bibbaseid":"bekker-fjellaksel-hjornevik-nuruddin-rafique-hansen-sundset-haraldsen-etal-discoveryofaleadbrainpenetratinggonadotropinreleasinghormonereceptorantagonistwithsaturablebindinginbrain-2020","authorIDs":[],"author_short":["Bekker, R. B. W.","Fjellaksel, R.","Hjornevik, T.","Nuruddin, S.","Rafique, W.","Hansen, J. H.","Sundset, R.","Haraldsen, I. H.","Riss, P. J."],"bibdata":{"bibtype":"article","type":"article","author":[{"propositions":[],"lastnames":["Bekker"],"firstnames":["Roberto","B.","W."],"suffixes":[]},{"propositions":[],"lastnames":["Fjellaksel"],"firstnames":["Richard"],"suffixes":[]},{"propositions":[],"lastnames":["Hjornevik"],"firstnames":["Trine"],"suffixes":[]},{"propositions":[],"lastnames":["Nuruddin"],"firstnames":["Syed"],"suffixes":[]},{"propositions":[],"lastnames":["Rafique"],"firstnames":["Waqas"],"suffixes":[]},{"propositions":[],"lastnames":["Hansen"],"firstnames":["Jørn","H."],"suffixes":[]},{"propositions":[],"lastnames":["Sundset"],"firstnames":["Rune"],"suffixes":[]},{"propositions":[],"lastnames":["Haraldsen"],"firstnames":["Ira","H."],"suffixes":[]},{"propositions":[],"lastnames":["Riss"],"firstnames":["Patrick","J."],"suffixes":[]}],"title":"Discovery of a Lead Brain-Penetrating Gonadotropin-Releasing Hormone Receptor Antagonist with Saturable Binding in Brain","journal":"ChemMedChem","volume":"15","number":"17","pages":"1624-1628","keywords":"elagolix, fluorine-18, GnRH−R, GnRH, PET","doi":"https://doi.org/10.1002/cmdc.202000256","url":"https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.202000256","eprint":"https://chemistry-europe.onlinelibrary.wiley.com/doi/pdf/10.1002/cmdc.202000256","abstract":"Abstract We report the synthesis, radiosynthesis and biological characterisation of two gonadotropin-releasing hormone receptor (GnRH−R) antagonists with nanomolar binding affinity. A small library of GnRH−R antagonists was synthesised in 20–67 % overall yield with the aim of identifying a high-affinity antagonist capable of crossing the blood–brain barrier. Binding affinity to rat GnRH−R was determined by autoradiography in competitive-binding studies against [125I]buserelin, and inhibition constants were calculated by using the Cheng–Prusoff equation. The radioligands were obtained in 46–79 % radiochemical yield and >95 % purity and with a molar activity of 19–38 MBq/nmol by direct nucleophilic radiofluorination. Positron emission tomography imaging in rat under baseline conditions in comparison to pretreatment with a receptor-saturating dose of GnRH antagonist revealed saturable uptake (0.1 %ID/mL) into the brain.","year":"2020","bibtex":"@article{https://doi.org/10.1002/cmdc.202000256,\nauthor = {Bekker, Roberto B. W. and Fjellaksel, Richard and Hjornevik, Trine and Nuruddin, Syed and Rafique, Waqas and Hansen, Jørn H. and Sundset, Rune and Haraldsen, Ira H. and Riss, Patrick J.},\ntitle = {Discovery of a Lead Brain-Penetrating Gonadotropin-Releasing Hormone Receptor Antagonist with Saturable Binding in Brain},\njournal = {ChemMedChem},\nvolume = {15},\nnumber = {17},\npages = {1624-1628},\nkeywords = {elagolix, fluorine-18, GnRH−R, GnRH, PET},\ndoi = {https://doi.org/10.1002/cmdc.202000256},\nurl = {https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.202000256},\neprint = {https://chemistry-europe.onlinelibrary.wiley.com/doi/pdf/10.1002/cmdc.202000256},\nabstract = {Abstract We report the synthesis, radiosynthesis and biological characterisation of two gonadotropin-releasing hormone receptor (GnRH−R) antagonists with nanomolar binding affinity. A small library of GnRH−R antagonists was synthesised in 20–67 \\% overall yield with the aim of identifying a high-affinity antagonist capable of crossing the blood–brain barrier. Binding affinity to rat GnRH−R was determined by autoradiography in competitive-binding studies against [125I]buserelin, and inhibition constants were calculated by using the Cheng–Prusoff equation. The radioligands were obtained in 46–79 \\% radiochemical yield and >95 \\% purity and with a molar activity of 19–38 MBq/nmol by direct nucleophilic radiofluorination. Positron emission tomography imaging in rat under baseline conditions in comparison to pretreatment with a receptor-saturating dose of GnRH antagonist revealed saturable uptake (0.1 \\%ID/mL) into the brain.},\nyear = {2020}\n}\n\n","author_short":["Bekker, R. B. W.","Fjellaksel, R.","Hjornevik, T.","Nuruddin, S.","Rafique, W.","Hansen, J. H.","Sundset, R.","Haraldsen, I. H.","Riss, P. J."],"key":"https://doi.org/10.1002/cmdc.202000256","id":"https://doi.org/10.1002/cmdc.202000256","bibbaseid":"bekker-fjellaksel-hjornevik-nuruddin-rafique-hansen-sundset-haraldsen-etal-discoveryofaleadbrainpenetratinggonadotropinreleasinghormonereceptorantagonistwithsaturablebindinginbrain-2020","role":"author","urls":{"Paper":"https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.202000256"},"keyword":["elagolix","fluorine-18","GnRH−R","GnRH","PET"],"metadata":{"authorlinks":{}},"downloads":0},"bibtype":"article","biburl":"https://drive.google.com/uc?id=1npQd_kFQJ1WhoHFdMxm9f24VTXXUJ6kw","creationDate":"2021-02-04T15:58:03.517Z","downloads":0,"keywords":["elagolix","fluorine-18","gnrh−r","gnrh","pet"],"search_terms":["discovery","lead","brain","penetrating","gonadotropin","releasing","hormone","receptor","antagonist","saturable","binding","brain","bekker","fjellaksel","hjornevik","nuruddin","rafique","hansen","sundset","haraldsen","riss"],"title":"Discovery of a Lead Brain-Penetrating Gonadotropin-Releasing Hormone Receptor Antagonist with Saturable Binding in Brain","year":2020,"dataSources":["oPYGjz5LJw7BLCPiK","qb42Xqdsuo5n9MtiJ","3HekLNYCKYdmLkjZH","XhEeRFbisz5SLRLws","EoffqxLuQbhKRpNmQ","P5LkHJDQ7GXibcCon"]}