Triazole oxytocin antagonists: Identification of an aryloxyazetidine replacement for a biaryl substituent

Brown, Alan D.; Brown, T. Bruce; Calabrese, Andrew; Ellis, Dave; Puhalo, Nicholas; Ralph, Michael J.; Watson, Lesa

doi:10.1016/j.bmcl.2009.11.097

Cited by 63 publications

(56 citation statements)

References 3 publications

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“…C25 (5‐(3‐(3‐(2‐chloro‐4‐fluorophenoxy)azetidin‐1‐yl)‐5‐(methoxymethyl)‐4H‐1,2,4‐triazol‐4‐yl)‐2‐methoxypyridine) and WAY 267,464 (4‐(3,5‐dihydroxybenzyl)‐N‐(2‐methyl‐4‐(1‐methyl‐1,4,5,10‐tetrahydrobenzo[β]pyrrolo[2,3‐e][1,4]diazepine‐5‐carbonyl)benzyl)piperazine‐1‐carboxamide) were synthesized according to the procedures of Brown et al . () and Hudson et al . (), respectively, and were considered to be of >95% purity according to proton, carbon nuclear magnetic resonance spectroscopy and mass spectrometry.…”

Section: Methodsmentioning

confidence: 99%

“…Here, we used biotelemetry to characterize the effects of peripherally administered OT, AVP and WAY 267,464 on body temperature and heart rate in freely moving rats. To determine the exact role of the OT and V1A receptors in the observed changes in body temperature and heart rate, we examined the antagonist effects of the selective non-peptide OT receptor antagonist Compound 25 (C25) (Brown et al, 2010;Ramos et al, 2013), and the selective non-peptide V1A receptor antagonist SR49059 (Serradeil-Le Gal et al, 1993). Finally, given the possibility that WAY 267,464 may have V1A receptor antagonist properties, we examined whether this compound might also antagonize some of the observed effects of OT and AVP.…”

Section: Introductionmentioning

confidence: 99%

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Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the non‐peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats

Hicks

Ramos

Reekie

et al. 2014

British J Pharmacology

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BACKGROUND AND PURPOSEThere is current interest in oxytocin (OT) as a possible therapeutic in psychiatric disorders. However, the usefulness of OT may be constrained by peripheral autonomic effects, which may involve an action at both OT and vasopressin V1A receptors. Here, we characterized the cardiovascular and thermoregulatory effects of OT, vasopressin (AVP) and the non-peptide OT receptor agonist WAY 267,464 in rats, and assessed the relative involvement of the OT and V1A receptors in these effects. EXPERIMENTAL APPROACHBiotelemetry in freely moving male Wistar rats was used to examine body temperature and heart rate after OT (0.01 -1 mg kg KEY RESULTSOT and AVP dose-dependently reduced body temperature and heart rate. WAY 267,464 had similar, but more modest, effects. SR49059, but not C25, prevented the hypothermia and bradycardia induced by OT and AVP. WAY 267,464 (100 mg·kg −1 ) prevented the effects of OT, and to some extent AVP. CONCLUSIONS AND IMPLICATIONSPeripherally administered OT and AVP have profound cardiovascular and thermoregulatory effects that appear to principally involve the V1A receptor rather than the OT receptor. Additionally, WAY 267,464 is not a simple OT receptor agonist, as it has functionally relevant V1A antagonist actions.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the non‐peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats

Hicks

Ramos

Reekie

et al. 2014

British J Pharmacology

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“…This hypothesis was supported by the fact that intracerebroventricular administration of tocinoic acid, an oxytocin receptor antagonist, blocked MDMA-induced adjacent lying. 99 However, in a follow-up study, McGregor and co-workers could not prevent MDMA-induced adjacent lying using C25, 116 a systemically administered non-peptidic antagonist of oxytocin receptors. In contrast, they were able to prevent this behavior using an antagonist of the vasopressin receptor 1A.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine

Dunlap

Andrews

Olson

2018

ACS Chem. Neurosci.

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Better known as “ecstasy,” 3,4-methylenedioxymethamphetamine (MDMA) is a small molecule that has played a prominent role in defining the ethos of today’s teenagers and young adults, much like lysergic acid diethylamide (LSD) did in the 1960s. Though MDMA possesses structural similarities to compounds like amphetamine and mescaline, it produces subjective effects that are unlike any of the classical psychostimulants or hallucinogens and is one of the few compounds capable of reliably producing prosocial behavioral states. As a result, MDMA has captured the attention of recreational users, the media, artists, psychiatrists, and neuropharmacologists alike. Here, we detail the synthesis of MDMA as well as its pharmacology, metabolism, adverse effects, and potential use in medicine. Finally, we discuss its history and why it is perhaps the most important compound for the future of psychedelic science—having the potential to either facilitate new psychedelic research initiatives, or to usher in a second Dark Age for the field.

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“…The cyclization of substituted hydrazide 73 with azetidine thioamide 74, a tautomeric form of S-methyl isothiourea, in the presence of trifluoroacetic acid produced compound 75 in low yield of 35% (Scheme 28) [108]. Further optimization of the reaction conditions to improve the yields of this transformation is necessary for potential clinical application of compound 75 as a potent oxytocin antagonist.…”

Section: Alkyl Hydrazidesmentioning

confidence: 99%

Current Developments in the Syntheses of 1,2,4-Triazole Compounds

Zhang¹,

Damu²,

Cai³

et al. 2014

COC

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Heterocyclic 1,2,4-triazole derivatives possess unusually spacious potentiality as medicinal agents, agricultural chemicals, functional materials, ionic liquids, supramolecular catalysts as well as artificial enzymes and receptors for supramolecular recognition and biomimetic catalysis, and their various researches and developments have been being a quite rapidly developing and active highlight topic with an infinite space. Numerous efforts have been directed toward various types of possible applications of 1,2,4-triazole-based compounds and a lot of important progress has been made, especially their preparations have attracted increasing attention. This review systematically summarized the recent advances in the syntheses of 1,2,4-triazole derivatives, including: (1) Cyclizations to form triazole ring; (2) Transformations of heterocyclic compounds to construct triazole ring; (3) Substitutions on 1,2,4-triazole ring; (4) Structural modifications in side chains of 1,2,4-triazole ring. It was hoped that this review would be helpful for the design and development of highly efficient preparation of 1,2,4-triazole derivatives with various sorts and varieties of extensively potential applications in medicine, agriculture, chemistry, materials, supramolecular sciences and so on.

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Triazole oxytocin antagonists: Identification of an aryloxyazetidine replacement for a biaryl substituent

Cited by 63 publications

References 3 publications

Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the non‐peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats

Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the non‐peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats

Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine

Current Developments in the Syntheses of 1,2,4-Triazole Compounds

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