Abstract:
:The five dopamine receptor subtypes (D1-5) are activated by the endogenous catecholamine dopamine. Sustained research has sought to identify selective ligands for receptor subtypes. In particular, activation of the D1 receptor has attracted attention due to its promising role in neurological diseases. Initial attempts to identify agonists yielded catechol derivatives, mimicking dopamine, with suboptimal DMPK parameters and low selectivity over the D5 subtype. However, more recent efforts to identify ligands capable of activating the D1 receptor have made substantial progress with the identification of non-catechol agonists with suitable properties to progress to clinical studies. In addition, several research groups have identified positive allosteric modulators that offer new potential. Furthermore, structural studies have surprisingly uncovered two potential allosteric binding sites, the most characterized of which appears to be on intracellular loop 2 (ICL2). This review highlights the recent progress in the field, covering both orthosteric and allosteric modes of activation, discusses the elucidation of the allosteric binding sites, and summarizes the clinical development status of various compounds.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Hall A,Provins L,Valade Adoi
10.1021/acs.jmedchem.8b01767subject
Has Abstractpub_date
2019-01-10 00:00:00pages
128-140issue
1eissn
0022-2623issn
1520-4804journal_volume
62pub_type
杂志文章,评审abstract::A comparison of the effects of the 6-(2-chloro-6-fluorobenzyl)-2-(alkylthio)pyrimidin-4(3H)-ones (2-Cl-6-F-S-DABOs) 7-12 and the related 6-(2,6-difluorobenzyl) counterparts 13-15 in HIV-1 infected cells and in the HIV-1 reverse transcriptase (RT) assays is here described. The new 2-Cl-6-F-S-DABOs showed up to picomola...
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journal_title:Journal of medicinal chemistry
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journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00385a024
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abstract::The enantiomers of the aminothiazole analogues of the known dopaminergic agonists apomorphine (1) and 2-aminohydroxytetralin (2) have been prepared. The absolute configurations of the enantiomers of 2,6-diaminotetrahydrobenzothiazole have been established by X-ray crystallographic analysis. Dopamine (DA) autoreceptor ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
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pub_type: 杂志文章
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abstract::The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b00424
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pub_type: 杂志文章
doi:10.1021/jm00222a004
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journal_title:Journal of medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2013-04-11 00:00:00
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journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00223a015
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journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00105a007
更新日期:1991-01-01 00:00:00
abstract::Tumors have evolved a variety of methods to reprogram conventional metabolic pathways to favor their own nutritional needs, including glutaminolysis, the first step of which is the hydrolysis of glutamine to glutamate by the amidohydrolase glutaminase 1 (GLS1). A GLS1 inhibitor could potentially target certain cancers...
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journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00386a024
更新日期:1987-03-01 00:00:00
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journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00105a003
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abstract::Benzocycloalkyl and benzocycloalkenyl moities linked, directly or via an alkyl chain, to oxygen-bearing heteroarylpiperazines were synthesized, in an attempt to obtain potent and selective antagonists at postsynaptic 5-HT1A receptors. From the numerous arylpiperazines described in the literature, 1-(2,3-dihydro-1,4-be...
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pub_type: 杂志文章
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