The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands
Authors
Elek, Milica
Frank, Annika

Đoković, Nemanja

Oljačić, Slavica

Živković, Aleksandra
Nikolić, Katarina

Stark, Holger

Conference object (Published version)

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Dopamine receptors are divided into two subclasses: D1 like receptors (D1 and D5 subtypes) and D2 like
receptors (D2, D3 and D4) [1]. Based on a general pharmacophore [2] we introduced the pentafluorosulfanyl
moiety (SF5-) group as an interesting pharmacological tool to investigate D2 like receptors. This moiety
displays high electronegativity and lipophilicity, while being thermally stable [3] and more resistant to
hydrolysis in comparison to that of other polyfuorinated moieties (e.g. CF3 or OCF3). Four novel compounds
with SF5 substituent have been synthesized, in silico and in vitro tested in order to examine their affinity
and selectivity towards human dopamine D2 and D3 receptor subtypes. All compounds showed high affinity
in the nanomolar concentration ranges at both receptors with ST 2200 expressing highest selectivity. In
silico examination determined high values of coefficient of determination (R2) and Spearman correlation
coefficient revealed good correlation betwee...n in silico parameters and experimentally obtained Ki values.
These results show that pentafluorosulfanyl substituent is a highly suitable moiety for structural variations
that has to be further investigated and could serve as novel substituent in numerous compound classes.
Source:
BOOK of ABSTRACTS MedChem19 Catanzaro, 2019, 66-66Publisher:
- Mu.Ta.Lig COST ACTION CA15135
- Paul Ehrlich Euro-PhD Network
Funding / projects:
- Mu.Ta.Lig COST ACTION CA15135
- Synthesis, Quantitative Structure and Activity Relationship, Physico-Chemical Characterisation and Analysis of Pharmacologically Active Substances (RS-172033)
Note:
- IV annual COST ACTION CA15135 meeting Paul Ehrlich Euro-PhD Network & MuTaLig COST Action meeting 2019, June 13th-15th 2019 Italy
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PharmacyTY - CONF AU - Elek, Milica AU - Frank, Annika AU - Đoković, Nemanja AU - Oljačić, Slavica AU - Živković, Aleksandra AU - Nikolić, Katarina AU - Stark, Holger PY - 2019 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4861 AB - Dopamine receptors are divided into two subclasses: D1 like receptors (D1 and D5 subtypes) and D2 like receptors (D2, D3 and D4) [1]. Based on a general pharmacophore [2] we introduced the pentafluorosulfanyl moiety (SF5-) group as an interesting pharmacological tool to investigate D2 like receptors. This moiety displays high electronegativity and lipophilicity, while being thermally stable [3] and more resistant to hydrolysis in comparison to that of other polyfuorinated moieties (e.g. CF3 or OCF3). Four novel compounds with SF5 substituent have been synthesized, in silico and in vitro tested in order to examine their affinity and selectivity towards human dopamine D2 and D3 receptor subtypes. All compounds showed high affinity in the nanomolar concentration ranges at both receptors with ST 2200 expressing highest selectivity. In silico examination determined high values of coefficient of determination (R2) and Spearman correlation coefficient revealed good correlation between in silico parameters and experimentally obtained Ki values. These results show that pentafluorosulfanyl substituent is a highly suitable moiety for structural variations that has to be further investigated and could serve as novel substituent in numerous compound classes. PB - Mu.Ta.Lig COST ACTION CA15135 PB - Paul Ehrlich Euro-PhD Network C3 - BOOK of ABSTRACTS MedChem19 Catanzaro T1 - The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands SP - 66 EP - 66 UR - https://hdl.handle.net/21.15107/rcub_farfar_4861 ER -
@conference{ author = "Elek, Milica and Frank, Annika and Đoković, Nemanja and Oljačić, Slavica and Živković, Aleksandra and Nikolić, Katarina and Stark, Holger", year = "2019", abstract = "Dopamine receptors are divided into two subclasses: D1 like receptors (D1 and D5 subtypes) and D2 like receptors (D2, D3 and D4) [1]. Based on a general pharmacophore [2] we introduced the pentafluorosulfanyl moiety (SF5-) group as an interesting pharmacological tool to investigate D2 like receptors. This moiety displays high electronegativity and lipophilicity, while being thermally stable [3] and more resistant to hydrolysis in comparison to that of other polyfuorinated moieties (e.g. CF3 or OCF3). Four novel compounds with SF5 substituent have been synthesized, in silico and in vitro tested in order to examine their affinity and selectivity towards human dopamine D2 and D3 receptor subtypes. All compounds showed high affinity in the nanomolar concentration ranges at both receptors with ST 2200 expressing highest selectivity. In silico examination determined high values of coefficient of determination (R2) and Spearman correlation coefficient revealed good correlation between in silico parameters and experimentally obtained Ki values. These results show that pentafluorosulfanyl substituent is a highly suitable moiety for structural variations that has to be further investigated and could serve as novel substituent in numerous compound classes.", publisher = "Mu.Ta.Lig COST ACTION CA15135, Paul Ehrlich Euro-PhD Network", journal = "BOOK of ABSTRACTS MedChem19 Catanzaro", title = "The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands", pages = "66-66", url = "https://hdl.handle.net/21.15107/rcub_farfar_4861" }
Elek, M., Frank, A., Đoković, N., Oljačić, S., Živković, A., Nikolić, K.,& Stark, H.. (2019). The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands. in BOOK of ABSTRACTS MedChem19 Catanzaro Mu.Ta.Lig COST ACTION CA15135., 66-66. https://hdl.handle.net/21.15107/rcub_farfar_4861
Elek M, Frank A, Đoković N, Oljačić S, Živković A, Nikolić K, Stark H. The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands. in BOOK of ABSTRACTS MedChem19 Catanzaro. 2019;:66-66. https://hdl.handle.net/21.15107/rcub_farfar_4861 .
Elek, Milica, Frank, Annika, Đoković, Nemanja, Oljačić, Slavica, Živković, Aleksandra, Nikolić, Katarina, Stark, Holger, "The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands" in BOOK of ABSTRACTS MedChem19 Catanzaro (2019):66-66, https://hdl.handle.net/21.15107/rcub_farfar_4861 .