Further SAR study on 11-O-substituted aporphine analogues: Identification of highly potent dopamine D3 receptor ligands

Ye, Na; Wu, Qianqian; Zhu, Liyuan; Zheng, Longtai; Gao, Bo; Zhen, Xuechu; Zhang, Ao

doi:10.1016/j.bmc.2011.01.053

Cited by 17 publications

(14 citation statements)

References 30 publications

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“…7-14 The aporphine chemotype may be regarded as a “privileged” CNS receptor template. Indeed, this scaffold represents an attractive opportunity to identify and develop selective mono-potent as well as multi-potent CNS receptor ligands for dopaminergic, adrenergic and serotonergic receptors.…”

Section: Introductionmentioning

confidence: 99%

New aporphinoid 5-HT2A and α1A antagonists via structural manipulations of nantenine

Chaudhary¹,

Ponnala²,

LeGendre³

et al. 2011

Bioorganic & Medicinal Chemistry

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A series of C1, C2, C3 and N6 analogs of nantenine (2) was synthesized and evaluated in 5-HT2A and α1A receptor functional assays. Alkyl substitution of the C1 and N6 methyl groups of nantenine provided selective 5-HT2A and α1A antagonists respectively. The C2 alkyloxy analogs studied were generally selective for α1A vs 5-HT2A. The C3 bromo analog 15 is one of the most potent aporphinoid 5-HT2A antagonists known presently.

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Section: Introductionmentioning

confidence: 99%

New aporphinoid 5-HT2A and α1A antagonists via structural manipulations of nantenine

Chaudhary¹,

Ponnala²,

LeGendre³

et al. 2011

Bioorganic & Medicinal Chemistry

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“…Considering that D 3 -preferring agonists provide an additional neuroprotective effect compared with D 2 -preferring agonists [ 82 – 86 ], multifunctional agents with D 3 agonistic activity have been developed to not only alleviate motor dysfunction in PD patients but also delay disease progression by protecting DA neurons from progressive degeneration. The Dutta group initially developed novel multifunctional agents with D 2 /D 3 agonist activity along with antioxidant and iron chelating activities and the ability to modulate αSN aggregation, such as (−)-19 [ 87 ], D512 [ 88 – 91 ], D-520 [ 92 , 93 ], D593 [ 44 ], D-607 [ 94 , 95 ], D636 [ 96 ], D653 [ 96 ], and D656 (Table 4 ) [ 96 ].…”

Section: Recent Advances In the Preclinical Study Of Dopaminergic Drumentioning

confidence: 99%

Recent advances in dopaminergic strategies for the treatment of Parkinson’s disease

et al. 2020

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s Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease worldwide. However, there is no available therapy reversing the neurodegenerative process of PD. Based on the loss of dopamine or dopaminergic dysfunction in PD patients, most of the current therapies focus on symptomatic relief to improve patient quality of life. As dopamine replacement treatment remains the most effective symptomatic pharmacotherapy for PD, herein we provide an overview of the current pharmacotherapies, summarize the clinical development status of novel dopaminergic agents, and highlight the challenge and opportunity of emerging preclinical dopaminergic approaches aimed at managing the features and progression of PD.

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“…27 These striatal MSNs also receive dense dopaminergic and glutamatergic signal inputs, 39,40 and this neural circuitry is strongly implicated in the etiology and treatment of Parkinson’s disease, Huntington’s disease, and also neuropsychiatric diseases. 41–46…”

Section: Gpr88 As a Potential Therapeutic Target For Human Cns Diseasesmentioning

confidence: 99%

Orphan Receptor GPR88 as an Emerging Neurotherapeutic Target

Mao

et al. 2018

ACS Chem. Neurosci.

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Although G protein-coupled receptors (GPCRs) are recognized as pivotal drug targets involved in multiple physiological and pathological processes, the majority of GPCRs including orphan GPCRs (oGPCRs) are unexploited. GPR88, a brain-specific oGPCR with particularly robust expression in the striatum, regulates diverse brain and behavioral functions, including cognition, mood, movement control, and reward-based learning, and is thus emerging as a novel drug target for central nervous system disorders including schizophrenia, Parkinson’s disease, anxiety, and addiction. Nevertheless, no effective GPR88 synthetic ligands have yet entered into clinical trials, and GPR88 endogenous ligands remain unknown. Despite the recent discovery and early stage study of several GPR88 agonists, such as 2-PCCA, RTI-13951–33, and phenylglycinol derivatives, further research into GPR88 pharmacology, medicinal chemistry, and chemical biology is urgently needed to yield structurally diversified GPR88-specific ligands. Drug-like pharmacological tool function and relevant signaling elucidation will also accelerate the evaluation of this receptor as a viable neurotherapeutic target.

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Further SAR study on 11-O-substituted aporphine analogues: Identification of highly potent dopamine D3 receptor ligands

Cited by 17 publications

References 30 publications

New aporphinoid 5-HT2A and α1A antagonists via structural manipulations of nantenine

New aporphinoid 5-HT2A and α1A antagonists via structural manipulations of nantenine

Recent advances in dopaminergic strategies for the treatment of Parkinson’s disease

Orphan Receptor GPR88 as an Emerging Neurotherapeutic Target

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