Synthesis and evaluation of potent and selective human V1a receptor antagonists as potential ligands for PET or SPECT imaging

Fabio, Karine; Guillon, Christophe; Lacey, C. Jeffrey; Lu, Shi-fang; Heindel, Ned D.; Ferris, Craig F.; Placzek, Michael S.; Jones, Graham B.; Brownstein, Michael J.; Simon, Neal G.

doi:10.1016/j.bmc.2011.12.013

Cited by 24 publications

(13 citation statements)

References 48 publications

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“…The lack of comparative studies in non-human and human primates with specific ligands and proper number of subjects highlights the need for further investigation into potential sex differences in brain V1aR expression in these species. Recently, a radiolabeled human V1aR antagonist has been developed for the use in PET and SPECT imaging, which may lead to a further understanding of sex differences in the brain V1aR system in humans, including the potential relation of V1aR binding with brain function and vasopressin-related disorders (Fabio et al, 2012). …”

Section: Sex Differences In Vasopressin and Oxytocin Receptors In mentioning

confidence: 99%

Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior

Dumais

Veenema

2016

Frontiers in Neuroendocrinology

417

350

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The neuropeptides vasopressin (VP) and oxytocin (OT) and their receptors in the brain are involved in the regulation of various social behaviors and have emerged as drug targets for the treatment of social dysfunction in several sex-biased neuropsychiatric disorders. Sex differences in the VP and OT systems may therefore be implicated in sex-specific regulation of healthy as well as impaired social behaviors. We begin this review by highlighting the sex differences, or lack of sex differences, in VP and OT synthesis in the brain. We then discuss the evidence showing the presence or absence of sex differences in VP and OT receptors in rodents and humans, as well as showing new data of sexually dimorphic V1a receptor binding in the rat brain. Importantly, we find that there is lack of comprehensive analysis of sex differences in these systems in common laboratory species, and we find that, when sex differences are present, they are highly brain region- and species- specific. Interestingly, VP system parameters (VP and V1aR) are typically higher in males, while sex differences in the OT system are not always in the same direction, often showing higher OT expression in females, but higher OT receptor expression in males. Furthermore, VP and OT receptor systems show distinct and largely non-overlapping expression in the rodent brain, which may cause these receptors to have either complementary or opposing functional roles in the sex-specific regulation of social behavior. Though still in need of further research, we close by discussing how manipulations of the VP and OT systems have given important insights into the involvement of these neuropeptide systems in the sex-specific regulation of social behavior in rodents and humans.

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Section: Sex Differences In Vasopressin and Oxytocin Receptors In mentioning

confidence: 99%

Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior

Dumais

Veenema

2016

Frontiers in Neuroendocrinology

417

350

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“…Synthesis of compounds 8a-l was achieved by the Suzuki reaction of the iodo-intermediates 3a, 3c-d with commercially available boronic acids or in-house prepared boronic esters 7 ( Schem e 3) [21].…”

Section: Resultsmentioning

confidence: 99%

“…A previous study [21] described the first V 1a PET radiotracers, but imaging studies in animals with these radiotracers have not been reported, possibly because of the suboptimal molecular weights (700–800 Dalton) of the radiotracers for sufficient blood-brain barrier permeability.…”

Section: Introductionmentioning

confidence: 99%

Development of a radioligand for imaging V 1a vasopressin receptors with PET

Naik

Valentine

Hall

et al. 2017

European Journal of Medicinal Chemistry

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A series of vasopressin receptor V ligands have been synthesized for positron emission tomography (PET) imaging. The lead compound (1S,5R)-1 ((4-(1H-indol-3-yl)-3-methoxyphenyl) ((1S,5R)-1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-yl)methanone) and its F-ethyl analog 6c exhibited the best combination of high binding affinity and optimal lipophilicity within the series. (1S,5R)-1 was radiolabeled with C for PET studies. [CH](1S,5R)-1 readily entered the mouse (4.7% ID/g tissue) and prairie vole brains (∼2% ID/g tissue) and specifically (30-34%) labeled V receptor. The common animal anesthetic Propofol significantly blocked the brain uptake of [CH](1S,5R)-1 in the mouse brain, whereas anesthetics Ketamine and Saffan increased the uptake variability. Future PET imaging studies with V radiotracers in non-human primates should be performed in awake animals or using anesthetics that do not affect the V receptor.

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“…Fabio et al 34 have developed a reliable method to prepare a versatile precursor that should allow access to both PET (18F, 11C) and SPECT (123I) derivatives of SRX246 {(R)-4-([1,4-Bipiperidin]-10-yl)-2-((2R,3S)-2-((E)-3-substitutedstyryl) -4 -oxo-3-((S)-2-oxo-4-phenyloxazoli din -3 -yl) azetidin-1-yl) -4 -oxo -N -((R) -1 -phenylethyl) Butanamides}29, a highly selective and potent hV1a antagonist.…”

Section: Vasopressin Via Antagonistmentioning

confidence: 99%

Untitled

2015

IJPSR

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Synthesis of heterocylic compound has always drawn the attention of chemist over the years mainly because of their important biological properties. Particularly, the role of β-lactam which are endowed with unique structure and potent biological activity. The β-lactam heterocycles are considered as an important contribution of science to humanity since they have been constituents of living organisms, natural products, drugs and many more substances useful to mankind and society in all walks of life. Their synthesis and evaluation has always drawn the attention of biologists over the years. β-lactam, a four member heterocyclic compound involved in research aimed to evaluate new products that possess interesting biological activities. Natural and synthetic β-lactam derivatives occupy a central place among medicinally important compounds due to their diverse and interesting antibiotic activities and are still the most prescribed antibiotics used in medicine. The present review article focuses on the pharmacological profile of β-lactam with their potential activities. The ring system exhibits a wide range of activities like antimicrobial, antitubercular, anticancer, antidiabetic, tryptase and chymase inhibitory activity etc. attracting the attention of researchers. The biological profile of β-lactam reported by organic chemist is reviewed here comprehensively with examples under eleven different activities.

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Synthesis and evaluation of potent and selective human V1a receptor antagonists as potential ligands for PET or SPECT imaging

Cited by 24 publications

References 48 publications

Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior

Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior

Development of a radioligand for imaging V 1a vasopressin receptors with PET

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