Evaluation of Substituted <i<N</i<-Phenylpiperazine Analogs as D3 vs. D2 Dopamine Receptor Subtype Selective Ligands

<i<N-</i<phenylpiperazine analogs can bind selectively to the D3 versus the D2 dopamine receptor subtype despite the fact that these two D2-like dopamine receptor subtypes exhibit substantial amino acid sequence homology. The binding for a number of these receptor subtype selective compo...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Boeun Lee [verfasserIn] Michelle Taylor [verfasserIn] Suzy A. Griffin [verfasserIn] Tamara McInnis [verfasserIn] Nathalie Sumien [verfasserIn] Robert H. Mach [verfasserIn] Robert R. Luedtke [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	D2-like dopamine receptors D3 dopamine receptor subtype G-protein coupled receptor (GPCR) dopamine receptor subtype selective ligands bitopic ligands

Übergeordnetes Werk:	In: Molecules - MDPI AG, 2003, 26(2021), 11, p 3182
Übergeordnetes Werk:	volume:26 ; year:2021 ; number:11, p 3182

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/molecules26113182

Katalog-ID:	DOAJ002737906

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allfieldsSound	10.3390/molecules26113182 doi (DE-627)DOAJ002737906 (DE-599)DOAJa3182d90e87b4adc85a60f89cdb4f171 DE-627 ger DE-627 rakwb eng QD241-441 Boeun Lee verfasserin aut Evaluation of Substituted <i<N</i<-Phenylpiperazine Analogs as D3 vs. D2 Dopamine Receptor Subtype Selective Ligands 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<N-</i<phenylpiperazine analogs can bind selectively to the D3 versus the D2 dopamine receptor subtype despite the fact that these two D2-like dopamine receptor subtypes exhibit substantial amino acid sequence homology. The binding for a number of these receptor subtype selective compounds was found to be consistent with their ability to bind at the D3 dopamine receptor subtype in a bitopic manner. In this study, a series of the 3-thiophenephenyl and 4-thiazolylphenyl fluoride substituted <i<N</i<-phenylpiperazine analogs were evaluated. Compound <b<6a</b< was found to bind at the human D3 receptor with nanomolar affinity with substantial D3 vs. D2 binding selectivity (approximately 500-fold). Compound <b<6a</b< was also tested for activity in two in-vivo assays: (1) a hallucinogenic-dependent head twitch response inhibition assay using DBA/2J mice and (2) an L-dopa-dependent abnormal involuntary movement (AIM) inhibition assay using unilateral 6-hydroxydopamine lesioned (hemiparkinsonian) rats. Compound <b<6a</b< was found to be active in both assays. This compound could lead to a better understanding of how a bitopic D3 dopamine receptor selective ligand might lead to the development of pharmacotherapeutics for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease. D2-like dopamine receptors D3 dopamine receptor subtype G-protein coupled receptor (GPCR) dopamine receptor subtype selective ligands bitopic ligands Organic chemistry Michelle Taylor verfasserin aut Suzy A. Griffin verfasserin aut Tamara McInnis verfasserin aut Nathalie Sumien verfasserin aut Robert H. Mach verfasserin aut Robert R. Luedtke verfasserin aut In Molecules MDPI AG, 2003 26(2021), 11, p 3182 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:26 year:2021 number:11, p 3182 https://doi.org/10.3390/molecules26113182 kostenfrei https://doaj.org/article/a3182d90e87b4adc85a60f89cdb4f171 kostenfrei https://www.mdpi.com/1420-3049/26/11/3182 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 26 2021 11, p 3182
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callnumber-first	Q - Science
author	Boeun Lee
spellingShingle	Boeun Lee misc QD241-441 misc D2-like dopamine receptors misc D3 dopamine receptor subtype misc G-protein coupled receptor (GPCR) misc dopamine receptor subtype selective ligands misc bitopic ligands misc Organic chemistry Evaluation of Substituted <i<N</i<-Phenylpiperazine Analogs as D3 vs. D2 Dopamine Receptor Subtype Selective Ligands
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topic_title	QD241-441 Evaluation of Substituted <i<N</i<-Phenylpiperazine Analogs as D3 vs. D2 Dopamine Receptor Subtype Selective Ligands D2-like dopamine receptors D3 dopamine receptor subtype G-protein coupled receptor (GPCR) dopamine receptor subtype selective ligands bitopic ligands
topic	misc QD241-441 misc D2-like dopamine receptors misc D3 dopamine receptor subtype misc G-protein coupled receptor (GPCR) misc dopamine receptor subtype selective ligands misc bitopic ligands misc Organic chemistry
topic_unstemmed	misc QD241-441 misc D2-like dopamine receptors misc D3 dopamine receptor subtype misc G-protein coupled receptor (GPCR) misc dopamine receptor subtype selective ligands misc bitopic ligands misc Organic chemistry
topic_browse	misc QD241-441 misc D2-like dopamine receptors misc D3 dopamine receptor subtype misc G-protein coupled receptor (GPCR) misc dopamine receptor subtype selective ligands misc bitopic ligands misc Organic chemistry
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title	Evaluation of Substituted <i<N</i<-Phenylpiperazine Analogs as D3 vs. D2 Dopamine Receptor Subtype Selective Ligands
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title_full	Evaluation of Substituted <i<N</i<-Phenylpiperazine Analogs as D3 vs. D2 Dopamine Receptor Subtype Selective Ligands
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title_sort	evaluation of substituted <i<n</i<-phenylpiperazine analogs as d3 vs. d2 dopamine receptor subtype selective ligands
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title_auth	Evaluation of Substituted <i<N</i<-Phenylpiperazine Analogs as D3 vs. D2 Dopamine Receptor Subtype Selective Ligands
abstract	<i<N-</i<phenylpiperazine analogs can bind selectively to the D3 versus the D2 dopamine receptor subtype despite the fact that these two D2-like dopamine receptor subtypes exhibit substantial amino acid sequence homology. The binding for a number of these receptor subtype selective compounds was found to be consistent with their ability to bind at the D3 dopamine receptor subtype in a bitopic manner. In this study, a series of the 3-thiophenephenyl and 4-thiazolylphenyl fluoride substituted <i<N</i<-phenylpiperazine analogs were evaluated. Compound <b<6a</b< was found to bind at the human D3 receptor with nanomolar affinity with substantial D3 vs. D2 binding selectivity (approximately 500-fold). Compound <b<6a</b< was also tested for activity in two in-vivo assays: (1) a hallucinogenic-dependent head twitch response inhibition assay using DBA/2J mice and (2) an L-dopa-dependent abnormal involuntary movement (AIM) inhibition assay using unilateral 6-hydroxydopamine lesioned (hemiparkinsonian) rats. Compound <b<6a</b< was found to be active in both assays. This compound could lead to a better understanding of how a bitopic D3 dopamine receptor selective ligand might lead to the development of pharmacotherapeutics for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease.
abstractGer	<i<N-</i<phenylpiperazine analogs can bind selectively to the D3 versus the D2 dopamine receptor subtype despite the fact that these two D2-like dopamine receptor subtypes exhibit substantial amino acid sequence homology. The binding for a number of these receptor subtype selective compounds was found to be consistent with their ability to bind at the D3 dopamine receptor subtype in a bitopic manner. In this study, a series of the 3-thiophenephenyl and 4-thiazolylphenyl fluoride substituted <i<N</i<-phenylpiperazine analogs were evaluated. Compound <b<6a</b< was found to bind at the human D3 receptor with nanomolar affinity with substantial D3 vs. D2 binding selectivity (approximately 500-fold). Compound <b<6a</b< was also tested for activity in two in-vivo assays: (1) a hallucinogenic-dependent head twitch response inhibition assay using DBA/2J mice and (2) an L-dopa-dependent abnormal involuntary movement (AIM) inhibition assay using unilateral 6-hydroxydopamine lesioned (hemiparkinsonian) rats. Compound <b<6a</b< was found to be active in both assays. This compound could lead to a better understanding of how a bitopic D3 dopamine receptor selective ligand might lead to the development of pharmacotherapeutics for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease.
abstract_unstemmed	<i<N-</i<phenylpiperazine analogs can bind selectively to the D3 versus the D2 dopamine receptor subtype despite the fact that these two D2-like dopamine receptor subtypes exhibit substantial amino acid sequence homology. The binding for a number of these receptor subtype selective compounds was found to be consistent with their ability to bind at the D3 dopamine receptor subtype in a bitopic manner. In this study, a series of the 3-thiophenephenyl and 4-thiazolylphenyl fluoride substituted <i<N</i<-phenylpiperazine analogs were evaluated. Compound <b<6a</b< was found to bind at the human D3 receptor with nanomolar affinity with substantial D3 vs. D2 binding selectivity (approximately 500-fold). Compound <b<6a</b< was also tested for activity in two in-vivo assays: (1) a hallucinogenic-dependent head twitch response inhibition assay using DBA/2J mice and (2) an L-dopa-dependent abnormal involuntary movement (AIM) inhibition assay using unilateral 6-hydroxydopamine lesioned (hemiparkinsonian) rats. Compound <b<6a</b< was found to be active in both assays. This compound could lead to a better understanding of how a bitopic D3 dopamine receptor selective ligand might lead to the development of pharmacotherapeutics for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease.
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title_short	Evaluation of Substituted <i<N</i<-Phenylpiperazine Analogs as D3 vs. D2 Dopamine Receptor Subtype Selective Ligands
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Evaluation of Substituted <i<N</i<-Phenylpiperazine Analogs as D3 vs. D2 Dopamine Receptor Subtype Selective Ligands

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