Recent Progress in Development of Dopamine Receptor Subtype-Selective Agents:  Potential Therapeutics for Neurological and Psychiatric Disorders

Ye, Na; Neumeyer, John L.; Baldessarini, Ross J.; Zhen, Xuechu; Zhang, Ao

doi:10.1021/cr050263h

Cited by 354 publications

(151 citation statements)

References 232 publications

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“…Sensitive detection of neurotransmitters is the cornerstone for advancing the understanding of neurological processes. 2 Dopamine and serotonin, which regulate numerous biological processes, are the most humanly important neurotransmitters. 3 Dopamine deficiency causes major clinical symptoms of Parkinson's disease (PD).…”

Section: * S Supporting Informationmentioning

confidence: 99%

Label-Free SERS Selective Detection of Dopamine and Serotonin Using Graphene-Au Nanopyramid Heterostructure

et al. 2015

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Ultrasensitive detection and spatially resolved mapping of neurotransmitters, dopamine and serotonin, are critical to facilitate understanding brain functions and investigate the information processing in neural networks. In this work, we demonstrated single molecule detection of dopamine and serotonin using a graphene–Au nanopyramid heterostructure platform. The quasi-periodic Au structure boosts high-density and high-homogeneity hotspots resulting in ultrahigh sensitivity with a surface enhanced Raman spectroscopic (SERS) enhancement factor ∼1010. A single layer graphene superimposed on a Au structure not only can locate SERS hot spots but also modify the surface chemistry to realize selective enhancement Raman yield. Dopamine and serotonin could be detected and distinguished from each other at 10–10 M level in 1 s data acquisition time without any pretreatment and labeling process. Moreover, the heterostructure realized nanomolar detection of neurotransmitters in the presence of simulated body fluids. These findings represent a step forward in enabling in-depth studies of neurological processes including those closely related to brain activity mapping (BAM).

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Section: * S Supporting Informationmentioning

confidence: 99%

Label-Free SERS Selective Detection of Dopamine and Serotonin Using Graphene-Au Nanopyramid Heterostructure

et al. 2015

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“…[9][10][11] SB269652 (1) 12,13 was recently described as the first small molecule negative allosteric modulator of the D 2 R. 13 This was somewhat surprising, given that 1 contains structural features of numerous orthosteric D 2 -like receptor ligands. 12,[14][15][16] Indeed, the 1,2,3,4-tetrahydroisoquinoline (THIQ) 'head' group of 1 contains a basic tertiary amine that is expected to form a salt bridge with the conserved aspartate (Asp 3.32 , Ballosteros-Weinstein nomenclature 17 ) of aminergic GPCRs, and would thus compete with the binding of dopamine.…”

Section: Introductionmentioning

confidence: 99%

Structure–Activity Study of N-((trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a Bitopic Ligand That Acts as a Negative Allosteric Modulator of the Dopamine D₂ Receptor

et al. 2015

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We recently demonstrated that SB269652 (1) engages one protomer of a dopamine D2 receptor (D2R) dimer in a bitopic mode to allosterically inhibit the binding of dopamine at the other protomer. Herein, we investigate structural determinants for allostery, focusing on modifications to three moieties within 1. We find that orthosteric “head” groups with small 7-substituents were important to maintain the limited negative cooperativity of analogues of 1, and replacement of the tetrahydroisoquinoline head group with other D2R “privileged structures” generated orthosteric antagonists. Additionally, replacement of the cyclohexylene linker with polymethylene chains conferred linker length dependency in allosteric pharmacology. We validated the importance of the indolic NH as a hydrogen bond donor moiety for maintaining allostery. Replacement of the indole ring with azaindole conferred a 30-fold increase in affinity while maintaining negative cooperativity. Combined, these results provide novel SAR insight for bitopic ligands that act as negative allosteric modulators of the D2R.

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“…10 Here, we report the synthesis and biological evaluation of (4-arylpiperazinyl)-piperidines as BACE 1 inhibitors.…”

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confidence: 99%

Synthesis and Biological Activities of (4-Arylpiperazinyl)piperidines as Nonpeptide BACE 1 Inhibitors

Poojary¹,

Won²,

Suh³

et al. 2011

Bulletin of the Korean Chemical Society

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Inhibition of BACE 1 activity is considered as a promising therapeutic target for Alzheimer's Disease (AD). Synthesis and inhibitory activities of (4-arylpiperazinyl)piperidines by bioisosteric replacement of a biaryl group with an arylpiperazine as BACE 1 inhibitors are described. The resulting (4-arylpiperazinyl)piperidines represent novel nonpeptide BACE 1 inhibitors with improved in vitro potency.

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Recent Progress in Development of Dopamine Receptor Subtype-Selective Agents: Potential Therapeutics for Neurological and Psychiatric Disorders

Cited by 354 publications

References 232 publications

Label-Free SERS Selective Detection of Dopamine and Serotonin Using Graphene-Au Nanopyramid Heterostructure

Label-Free SERS Selective Detection of Dopamine and Serotonin Using Graphene-Au Nanopyramid Heterostructure

Structure–Activity Study of N-((trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a Bitopic Ligand That Acts as a Negative Allosteric Modulator of the Dopamine D₂ Receptor

Synthesis and Biological Activities of (4-Arylpiperazinyl)piperidines as Nonpeptide BACE 1 Inhibitors

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Recent Progress in Development of Dopamine Receptor Subtype-Selective Agents: Potential Therapeutics for Neurological and Psychiatric Disorders

Cited by 354 publications

References 232 publications

Label-Free SERS Selective Detection of Dopamine and Serotonin Using Graphene-Au Nanopyramid Heterostructure

Label-Free SERS Selective Detection of Dopamine and Serotonin Using Graphene-Au Nanopyramid Heterostructure

Structure–Activity Study of N-((trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a Bitopic Ligand That Acts as a Negative Allosteric Modulator of the Dopamine D2 Receptor

Synthesis and Biological Activities of (4-Arylpiperazinyl)piperidines as Nonpeptide BACE 1 Inhibitors

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Structure–Activity Study of N-((trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a Bitopic Ligand That Acts as a Negative Allosteric Modulator of the Dopamine D₂ Receptor