<i<N</i<-[1,3-Dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulphonamides as Novel Selective Human Cannabinoid Type 2 Receptor (hCB2R) Ligands; Insights into the Mechanism of Receptor Activation/Deactivation

Cannabinoid type 1 (hCB1) and type 2 (hCB2) receptors are pleiotropic and crucial targets whose signaling contributes to physiological homeostasis and its restoration after injury. Being predominantly expressed in peripheral tissues, hCB2R represents a safer therapeutic target than hCB1R, which is h...
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Autor*in:	Eleonora Gianquinto [verfasserIn] Federica Sodano [verfasserIn] Barbara Rolando [verfasserIn] Magdalena Kostrzewa [verfasserIn] Marco Allarà [verfasserIn] Ali Mokhtar Mahmoud [verfasserIn] Poulami Kumar [verfasserIn] Francesca Spyrakis [verfasserIn] Alessia Ligresti [verfasserIn] Konstantin Chegaev [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	cannabinoid receptors hCB2R selective ligands drug design in silico simulations mechanism of receptor activation

Übergeordnetes Werk:	In: Molecules - MDPI AG, 2003, 27(2022), 23, p 8152
Übergeordnetes Werk:	volume:27 ; year:2022 ; number:23, p 8152

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/molecules27238152

Katalog-ID:	DOAJ083410392

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allfields	10.3390/molecules27238152 doi (DE-627)DOAJ083410392 (DE-599)DOAJ30fb8dde4c70493698c84d4204fa91ed DE-627 ger DE-627 rakwb eng QD241-441 Eleonora Gianquinto verfasserin aut <i<N</i<-[1,3-Dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulphonamides as Novel Selective Human Cannabinoid Type 2 Receptor (hCB2R) Ligands; Insights into the Mechanism of Receptor Activation/Deactivation 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cannabinoid type 1 (hCB1) and type 2 (hCB2) receptors are pleiotropic and crucial targets whose signaling contributes to physiological homeostasis and its restoration after injury. Being predominantly expressed in peripheral tissues, hCB2R represents a safer therapeutic target than hCB1R, which is highly expressed in the brain, where it regulates processes related to cognition, memory, and motor control. The development of hCB2R ligands represents a therapeutic opportunity for treating diseases such as pain, inflammation and cancer. Identifying new selective scaffolds for cannabinoids and determining the structural determinants responsible for agonism and antagonism are priorities in drug design. In this work, a series of <i<N</i<-[1,3-dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulfonamides is designed and synthesized and their affinity for human hCB1R and hCB2R is determined. Starting with a scaffold selected from the NIH Psychoactive Drug Screening Program Repository, through a combination of molecular modeling and structure–activity relationship studies, we were able to identify the chemical features leading to finely tuned hCB2R selectivity. In addition, an in silico model capable of predicting the functional activity of hCB2R ligands was proposed and validated. The proposed receptor activation/deactivation model enabled the identification of four pure hCB2R-selective agonists that can be used as a starting point for the development of more potent ligands. cannabinoid receptors hCB2R selective ligands drug design in silico simulations mechanism of receptor activation Organic chemistry Federica Sodano verfasserin aut Barbara Rolando verfasserin aut Magdalena Kostrzewa verfasserin aut Marco Allarà verfasserin aut Ali Mokhtar Mahmoud verfasserin aut Poulami Kumar verfasserin aut Francesca Spyrakis verfasserin aut Alessia Ligresti verfasserin aut Konstantin Chegaev verfasserin aut In Molecules MDPI AG, 2003 27(2022), 23, p 8152 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:27 year:2022 number:23, p 8152 https://doi.org/10.3390/molecules27238152 kostenfrei https://doaj.org/article/30fb8dde4c70493698c84d4204fa91ed kostenfrei https://www.mdpi.com/1420-3049/27/23/8152 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 27 2022 23, p 8152
spelling	10.3390/molecules27238152 doi (DE-627)DOAJ083410392 (DE-599)DOAJ30fb8dde4c70493698c84d4204fa91ed DE-627 ger DE-627 rakwb eng QD241-441 Eleonora Gianquinto verfasserin aut <i<N</i<-[1,3-Dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulphonamides as Novel Selective Human Cannabinoid Type 2 Receptor (hCB2R) Ligands; Insights into the Mechanism of Receptor Activation/Deactivation 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cannabinoid type 1 (hCB1) and type 2 (hCB2) receptors are pleiotropic and crucial targets whose signaling contributes to physiological homeostasis and its restoration after injury. Being predominantly expressed in peripheral tissues, hCB2R represents a safer therapeutic target than hCB1R, which is highly expressed in the brain, where it regulates processes related to cognition, memory, and motor control. The development of hCB2R ligands represents a therapeutic opportunity for treating diseases such as pain, inflammation and cancer. Identifying new selective scaffolds for cannabinoids and determining the structural determinants responsible for agonism and antagonism are priorities in drug design. In this work, a series of <i<N</i<-[1,3-dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulfonamides is designed and synthesized and their affinity for human hCB1R and hCB2R is determined. Starting with a scaffold selected from the NIH Psychoactive Drug Screening Program Repository, through a combination of molecular modeling and structure–activity relationship studies, we were able to identify the chemical features leading to finely tuned hCB2R selectivity. In addition, an in silico model capable of predicting the functional activity of hCB2R ligands was proposed and validated. The proposed receptor activation/deactivation model enabled the identification of four pure hCB2R-selective agonists that can be used as a starting point for the development of more potent ligands. cannabinoid receptors hCB2R selective ligands drug design in silico simulations mechanism of receptor activation Organic chemistry Federica Sodano verfasserin aut Barbara Rolando verfasserin aut Magdalena Kostrzewa verfasserin aut Marco Allarà verfasserin aut Ali Mokhtar Mahmoud verfasserin aut Poulami Kumar verfasserin aut Francesca Spyrakis verfasserin aut Alessia Ligresti verfasserin aut Konstantin Chegaev verfasserin aut In Molecules MDPI AG, 2003 27(2022), 23, p 8152 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:27 year:2022 number:23, p 8152 https://doi.org/10.3390/molecules27238152 kostenfrei https://doaj.org/article/30fb8dde4c70493698c84d4204fa91ed kostenfrei https://www.mdpi.com/1420-3049/27/23/8152 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 27 2022 23, p 8152
allfields_unstemmed	10.3390/molecules27238152 doi (DE-627)DOAJ083410392 (DE-599)DOAJ30fb8dde4c70493698c84d4204fa91ed DE-627 ger DE-627 rakwb eng QD241-441 Eleonora Gianquinto verfasserin aut <i<N</i<-[1,3-Dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulphonamides as Novel Selective Human Cannabinoid Type 2 Receptor (hCB2R) Ligands; Insights into the Mechanism of Receptor Activation/Deactivation 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cannabinoid type 1 (hCB1) and type 2 (hCB2) receptors are pleiotropic and crucial targets whose signaling contributes to physiological homeostasis and its restoration after injury. Being predominantly expressed in peripheral tissues, hCB2R represents a safer therapeutic target than hCB1R, which is highly expressed in the brain, where it regulates processes related to cognition, memory, and motor control. The development of hCB2R ligands represents a therapeutic opportunity for treating diseases such as pain, inflammation and cancer. Identifying new selective scaffolds for cannabinoids and determining the structural determinants responsible for agonism and antagonism are priorities in drug design. In this work, a series of <i<N</i<-[1,3-dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulfonamides is designed and synthesized and their affinity for human hCB1R and hCB2R is determined. Starting with a scaffold selected from the NIH Psychoactive Drug Screening Program Repository, through a combination of molecular modeling and structure–activity relationship studies, we were able to identify the chemical features leading to finely tuned hCB2R selectivity. In addition, an in silico model capable of predicting the functional activity of hCB2R ligands was proposed and validated. The proposed receptor activation/deactivation model enabled the identification of four pure hCB2R-selective agonists that can be used as a starting point for the development of more potent ligands. cannabinoid receptors hCB2R selective ligands drug design in silico simulations mechanism of receptor activation Organic chemistry Federica Sodano verfasserin aut Barbara Rolando verfasserin aut Magdalena Kostrzewa verfasserin aut Marco Allarà verfasserin aut Ali Mokhtar Mahmoud verfasserin aut Poulami Kumar verfasserin aut Francesca Spyrakis verfasserin aut Alessia Ligresti verfasserin aut Konstantin Chegaev verfasserin aut In Molecules MDPI AG, 2003 27(2022), 23, p 8152 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:27 year:2022 number:23, p 8152 https://doi.org/10.3390/molecules27238152 kostenfrei https://doaj.org/article/30fb8dde4c70493698c84d4204fa91ed kostenfrei https://www.mdpi.com/1420-3049/27/23/8152 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 27 2022 23, p 8152
allfieldsGer	10.3390/molecules27238152 doi (DE-627)DOAJ083410392 (DE-599)DOAJ30fb8dde4c70493698c84d4204fa91ed DE-627 ger DE-627 rakwb eng QD241-441 Eleonora Gianquinto verfasserin aut <i<N</i<-[1,3-Dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulphonamides as Novel Selective Human Cannabinoid Type 2 Receptor (hCB2R) Ligands; Insights into the Mechanism of Receptor Activation/Deactivation 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cannabinoid type 1 (hCB1) and type 2 (hCB2) receptors are pleiotropic and crucial targets whose signaling contributes to physiological homeostasis and its restoration after injury. Being predominantly expressed in peripheral tissues, hCB2R represents a safer therapeutic target than hCB1R, which is highly expressed in the brain, where it regulates processes related to cognition, memory, and motor control. The development of hCB2R ligands represents a therapeutic opportunity for treating diseases such as pain, inflammation and cancer. Identifying new selective scaffolds for cannabinoids and determining the structural determinants responsible for agonism and antagonism are priorities in drug design. In this work, a series of <i<N</i<-[1,3-dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulfonamides is designed and synthesized and their affinity for human hCB1R and hCB2R is determined. Starting with a scaffold selected from the NIH Psychoactive Drug Screening Program Repository, through a combination of molecular modeling and structure–activity relationship studies, we were able to identify the chemical features leading to finely tuned hCB2R selectivity. In addition, an in silico model capable of predicting the functional activity of hCB2R ligands was proposed and validated. The proposed receptor activation/deactivation model enabled the identification of four pure hCB2R-selective agonists that can be used as a starting point for the development of more potent ligands. cannabinoid receptors hCB2R selective ligands drug design in silico simulations mechanism of receptor activation Organic chemistry Federica Sodano verfasserin aut Barbara Rolando verfasserin aut Magdalena Kostrzewa verfasserin aut Marco Allarà verfasserin aut Ali Mokhtar Mahmoud verfasserin aut Poulami Kumar verfasserin aut Francesca Spyrakis verfasserin aut Alessia Ligresti verfasserin aut Konstantin Chegaev verfasserin aut In Molecules MDPI AG, 2003 27(2022), 23, p 8152 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:27 year:2022 number:23, p 8152 https://doi.org/10.3390/molecules27238152 kostenfrei https://doaj.org/article/30fb8dde4c70493698c84d4204fa91ed kostenfrei https://www.mdpi.com/1420-3049/27/23/8152 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 27 2022 23, p 8152
allfieldsSound	10.3390/molecules27238152 doi (DE-627)DOAJ083410392 (DE-599)DOAJ30fb8dde4c70493698c84d4204fa91ed DE-627 ger DE-627 rakwb eng QD241-441 Eleonora Gianquinto verfasserin aut <i<N</i<-[1,3-Dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulphonamides as Novel Selective Human Cannabinoid Type 2 Receptor (hCB2R) Ligands; Insights into the Mechanism of Receptor Activation/Deactivation 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cannabinoid type 1 (hCB1) and type 2 (hCB2) receptors are pleiotropic and crucial targets whose signaling contributes to physiological homeostasis and its restoration after injury. Being predominantly expressed in peripheral tissues, hCB2R represents a safer therapeutic target than hCB1R, which is highly expressed in the brain, where it regulates processes related to cognition, memory, and motor control. The development of hCB2R ligands represents a therapeutic opportunity for treating diseases such as pain, inflammation and cancer. Identifying new selective scaffolds for cannabinoids and determining the structural determinants responsible for agonism and antagonism are priorities in drug design. In this work, a series of <i<N</i<-[1,3-dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulfonamides is designed and synthesized and their affinity for human hCB1R and hCB2R is determined. Starting with a scaffold selected from the NIH Psychoactive Drug Screening Program Repository, through a combination of molecular modeling and structure–activity relationship studies, we were able to identify the chemical features leading to finely tuned hCB2R selectivity. In addition, an in silico model capable of predicting the functional activity of hCB2R ligands was proposed and validated. The proposed receptor activation/deactivation model enabled the identification of four pure hCB2R-selective agonists that can be used as a starting point for the development of more potent ligands. cannabinoid receptors hCB2R selective ligands drug design in silico simulations mechanism of receptor activation Organic chemistry Federica Sodano verfasserin aut Barbara Rolando verfasserin aut Magdalena Kostrzewa verfasserin aut Marco Allarà verfasserin aut Ali Mokhtar Mahmoud verfasserin aut Poulami Kumar verfasserin aut Francesca Spyrakis verfasserin aut Alessia Ligresti verfasserin aut Konstantin Chegaev verfasserin aut In Molecules MDPI AG, 2003 27(2022), 23, p 8152 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:27 year:2022 number:23, p 8152 https://doi.org/10.3390/molecules27238152 kostenfrei https://doaj.org/article/30fb8dde4c70493698c84d4204fa91ed kostenfrei https://www.mdpi.com/1420-3049/27/23/8152 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 27 2022 23, p 8152
language	English
source	In Molecules 27(2022), 23, p 8152 volume:27 year:2022 number:23, p 8152
sourceStr	In Molecules 27(2022), 23, p 8152 volume:27 year:2022 number:23, p 8152
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	cannabinoid receptors hCB2R selective ligands drug design in silico simulations mechanism of receptor activation Organic chemistry
isfreeaccess_bool	true
container_title	Molecules
authorswithroles_txt_mv	Eleonora Gianquinto @@aut@@ Federica Sodano @@aut@@ Barbara Rolando @@aut@@ Magdalena Kostrzewa @@aut@@ Marco Allarà @@aut@@ Ali Mokhtar Mahmoud @@aut@@ Poulami Kumar @@aut@@ Francesca Spyrakis @@aut@@ Alessia Ligresti @@aut@@ Konstantin Chegaev @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	311313132
id	DOAJ083410392
language_de	englisch
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callnumber-first	Q - Science
author	Eleonora Gianquinto
spellingShingle	Eleonora Gianquinto misc QD241-441 misc cannabinoid receptors misc hCB2R selective ligands misc drug design misc in silico simulations misc mechanism of receptor activation misc Organic chemistry <i<N</i<-[1,3-Dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulphonamides as Novel Selective Human Cannabinoid Type 2 Receptor (hCB2R) Ligands; Insights into the Mechanism of Receptor Activation/Deactivation
authorStr	Eleonora Gianquinto
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topic_title	QD241-441 <i<N</i<-[1,3-Dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulphonamides as Novel Selective Human Cannabinoid Type 2 Receptor (hCB2R) Ligands; Insights into the Mechanism of Receptor Activation/Deactivation cannabinoid receptors hCB2R selective ligands drug design in silico simulations mechanism of receptor activation
topic	misc QD241-441 misc cannabinoid receptors misc hCB2R selective ligands misc drug design misc in silico simulations misc mechanism of receptor activation misc Organic chemistry
topic_unstemmed	misc QD241-441 misc cannabinoid receptors misc hCB2R selective ligands misc drug design misc in silico simulations misc mechanism of receptor activation misc Organic chemistry
topic_browse	misc QD241-441 misc cannabinoid receptors misc hCB2R selective ligands misc drug design misc in silico simulations misc mechanism of receptor activation misc Organic chemistry
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title	<i<N</i<-[1,3-Dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulphonamides as Novel Selective Human Cannabinoid Type 2 Receptor (hCB2R) Ligands; Insights into the Mechanism of Receptor Activation/Deactivation
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title_full	<i<N</i<-[1,3-Dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulphonamides as Novel Selective Human Cannabinoid Type 2 Receptor (hCB2R) Ligands; Insights into the Mechanism of Receptor Activation/Deactivation
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author_browse	Eleonora Gianquinto Federica Sodano Barbara Rolando Magdalena Kostrzewa Marco Allarà Ali Mokhtar Mahmoud Poulami Kumar Francesca Spyrakis Alessia Ligresti Konstantin Chegaev
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author-letter	Eleonora Gianquinto
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title_sort	<i<n</i<-[1,3-dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulphonamides as novel selective human cannabinoid type 2 receptor (hcb2r) ligands; insights into the mechanism of receptor activation/deactivation
callnumber	QD241-441
title_auth	<i<N</i<-[1,3-Dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulphonamides as Novel Selective Human Cannabinoid Type 2 Receptor (hCB2R) Ligands; Insights into the Mechanism of Receptor Activation/Deactivation
abstract	Cannabinoid type 1 (hCB1) and type 2 (hCB2) receptors are pleiotropic and crucial targets whose signaling contributes to physiological homeostasis and its restoration after injury. Being predominantly expressed in peripheral tissues, hCB2R represents a safer therapeutic target than hCB1R, which is highly expressed in the brain, where it regulates processes related to cognition, memory, and motor control. The development of hCB2R ligands represents a therapeutic opportunity for treating diseases such as pain, inflammation and cancer. Identifying new selective scaffolds for cannabinoids and determining the structural determinants responsible for agonism and antagonism are priorities in drug design. In this work, a series of <i<N</i<-[1,3-dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulfonamides is designed and synthesized and their affinity for human hCB1R and hCB2R is determined. Starting with a scaffold selected from the NIH Psychoactive Drug Screening Program Repository, through a combination of molecular modeling and structure–activity relationship studies, we were able to identify the chemical features leading to finely tuned hCB2R selectivity. In addition, an in silico model capable of predicting the functional activity of hCB2R ligands was proposed and validated. The proposed receptor activation/deactivation model enabled the identification of four pure hCB2R-selective agonists that can be used as a starting point for the development of more potent ligands.
abstractGer	Cannabinoid type 1 (hCB1) and type 2 (hCB2) receptors are pleiotropic and crucial targets whose signaling contributes to physiological homeostasis and its restoration after injury. Being predominantly expressed in peripheral tissues, hCB2R represents a safer therapeutic target than hCB1R, which is highly expressed in the brain, where it regulates processes related to cognition, memory, and motor control. The development of hCB2R ligands represents a therapeutic opportunity for treating diseases such as pain, inflammation and cancer. Identifying new selective scaffolds for cannabinoids and determining the structural determinants responsible for agonism and antagonism are priorities in drug design. In this work, a series of <i<N</i<-[1,3-dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulfonamides is designed and synthesized and their affinity for human hCB1R and hCB2R is determined. Starting with a scaffold selected from the NIH Psychoactive Drug Screening Program Repository, through a combination of molecular modeling and structure–activity relationship studies, we were able to identify the chemical features leading to finely tuned hCB2R selectivity. In addition, an in silico model capable of predicting the functional activity of hCB2R ligands was proposed and validated. The proposed receptor activation/deactivation model enabled the identification of four pure hCB2R-selective agonists that can be used as a starting point for the development of more potent ligands.
abstract_unstemmed	Cannabinoid type 1 (hCB1) and type 2 (hCB2) receptors are pleiotropic and crucial targets whose signaling contributes to physiological homeostasis and its restoration after injury. Being predominantly expressed in peripheral tissues, hCB2R represents a safer therapeutic target than hCB1R, which is highly expressed in the brain, where it regulates processes related to cognition, memory, and motor control. The development of hCB2R ligands represents a therapeutic opportunity for treating diseases such as pain, inflammation and cancer. Identifying new selective scaffolds for cannabinoids and determining the structural determinants responsible for agonism and antagonism are priorities in drug design. In this work, a series of <i<N</i<-[1,3-dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulfonamides is designed and synthesized and their affinity for human hCB1R and hCB2R is determined. Starting with a scaffold selected from the NIH Psychoactive Drug Screening Program Repository, through a combination of molecular modeling and structure–activity relationship studies, we were able to identify the chemical features leading to finely tuned hCB2R selectivity. In addition, an in silico model capable of predicting the functional activity of hCB2R ligands was proposed and validated. The proposed receptor activation/deactivation model enabled the identification of four pure hCB2R-selective agonists that can be used as a starting point for the development of more potent ligands.
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title_short	<i<N</i<-[1,3-Dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulphonamides as Novel Selective Human Cannabinoid Type 2 Receptor (hCB2R) Ligands; Insights into the Mechanism of Receptor Activation/Deactivation
url	https://doi.org/10.3390/molecules27238152 https://doaj.org/article/30fb8dde4c70493698c84d4204fa91ed https://www.mdpi.com/1420-3049/27/23/8152 https://doaj.org/toc/1420-3049
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author2	Federica Sodano Barbara Rolando Magdalena Kostrzewa Marco Allarà Ali Mokhtar Mahmoud Poulami Kumar Francesca Spyrakis Alessia Ligresti Konstantin Chegaev
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