The synthesis and vasopressin (AVP) antagonist activity of a novel series of n -aroyl-2,4,5,6-tetrahydropyrazolo [3,4- d ]thieno[3,2- b ]azepines

Albright, J. Donald; Santos, Efren G. Delos; Dusza, John P.; Chan, Peter S.; Coupet, Joseph; Ru, Xun; Mazandarani, Hossein

doi:10.1016/s0960-894x(00)00084-6

Cited by 23 publications

(4 citation statements)

References 16 publications

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“…However, some of them do show selectivity for V1b receptors ( Table 1). Most of the compounds were characterized by receptor binding assays, and a few have already Benzazepine-furanilides (YM218) [46] Benzazepine-benzanilides [48] N-Methylbenzanilides [49] Triazoles [49] oxindoles [37][38][39] 2,5-disubstituted benzothiazepines [50] indoloazepines [51] benzodiazepine ring fused to a bridged bicyclic amine [53] quinoxaline (vp-343) [54] benzodiazepines [52,55] benzodiazepine ring fused to a bridged bicyclic amine [53] benzoazepines [22,45,47,55,56] thienoazepines [41] thiazepines and thiazines [57,58] Cell. Mol.…”

Section: Chemical Structure and Selectivity Of In Vivo And In Vitro Tmentioning

confidence: 99%

Vasopressin antagonists

Lemmens‐Gruber

Kamyar

2006

Cell. Mol. Life Sci.

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Effects of vasopressin via V1a- and V2-receptors are closely implicated in a variety of water-retaining diseases and cardiovascular diseases, including heart failure, hyponatraemia, hypertension, renal diseases, syndrome of inappropriate antidiuretic hormone secretion, cirrhosis and ocular hypertension. As vasopressin receptors are found in many different tissues, vasopressin antagonists may benefit the treatment of disorders such as cerebral ischaemia and stroke, Raynaud's disease, dysmenorrhoea and tocolytic treatment. V1b selective vasopressin antagonists are discussed in terms of their usefulness in the treatment of emotional and psychiatric disorders. The vaptans are vasopressin receptor antagonists with V1a (relcovaptan) or V2 (tolvaptan, lixivaptan) selectivity or non-selective activity (conivaptan) which may be advantageous in some disorders. The V1a/V2 non-selective vasopressin antagonist conivaptan is the first vaptan which is approved by the FDA for the treatment of euvolaemic hyponatraemia.

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Section: Chemical Structure and Selectivity Of In Vivo And In Vitro Tmentioning

confidence: 99%

Vasopressin antagonists

Lemmens‐Gruber

Kamyar

2006

Cell. Mol. Life Sci.

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“…Strutturalmente gli acquaretici sono benzazepine, derivati delle benzamidi, più precisamente fenil-benzamidi, in cui è il gruppo fenolico a conferire alla benzamide una forte attività antagonista dei recettori dell'AVP [15].…”

Section: Chimicaunclassified

The aquaretics in the treatment of hyponatremia

Portioli¹

2013

Ital J Med

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Gli acquaretici sono antagonisti non peptidici del recettore V2 dell'arginina-vasopressina (AVP) che inducono diuresi di acqua libera senza natriuresi e senza kaliuresi. Obiettivo del loro possibile impiego in terapia è la correzione della iponatriemia.L'iponatriemia (concentrazione di sodio sierico < 135 mMol/L) -il disturbo elettrolitico più frequente in clinicaè presente nel 15-20% dei pazienti ospedalizzati e nelle sue forme gravi si associa a un aumento di morbilità e di mortalità. Nello scompenso di cuore [1,2], nella cirrosi scompensata [3], nel decorso post-trapianto di fegato [4] o dell'infarto miocardico con ST elevata [5] l'iponatriemia ha peso prognostico tale da indurre Schrier [6] a definirla "un predittore di morte".Le iponatriemie minori peggiorano il decorso dello scompenso di cuore o della cirrosi epatica e, se cronicizzate, provocano disturbi neurologici importanti, ma reversibili, dell'equilibrio e dell'attenzione, che possono comportare aumento delle cadute [7], fatto rilevante data l'alta prevalenza di iponatriemia nei soggetti in residenze sanitario-assistenziali [8].In tutte queste condizioni la secrezione di AVP ha un ruolo centrale, ma a tutt'oggi la correzione dell'iponatriemia si è valsa di strumenti indiretti, o fortuiti. Pressoché tutti gli approcci intesi a correggerla hanno efficacia molto variabile ed effetti collaterali importanti.La restrizione di liquidi può essere difficile da praticare perché è lenta ad agire ed è mal tollerata specie quando deve essere continuata, come accade nella realtà clinica, per lunghi periodi di tempo e da pazienti non ospedalizzati; è, soprattutto, inefficace come dimostra il primo studio controllato sul tema [9].Se il paziente ha una buona funzione renale il trattamento ideale dell'iponatriemia è costituito dal blocco dei recettori renali per la vasopressina. La dimetil-clor-tetraciclina (demeclociclina), che ritarda l'azione antidiuretica dell'AVP inibendo l'AMP-ciclico nei tubuli collettori renali, è farmaco di scelta ma non si usa perché provoca insufficienza renale. Il litio ha effetti analoghi, ma è anche meno costante nell'azione e ha effetti collaterali di rilievo: renali, car-

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“…(12)], exemplified by the prototype compound VPA-985 (48) [304] and variants thereof, such as 49 [305,306,307], reminiscent of Yamanouchi's YM-086 (42). These compounds are reported to be V1a/V2-antagonists, with varying degrees of V2-specificity, but OT-R activities are claimed and sometimes also disclosed in the corresponding patents [308].…”

Section: Non-peptide Antagonistsmentioning

confidence: 99%

Preterm Labour: An Overview of Current and Emerging Therapeutics

Schwarz¹,

Page²

2003

CMC

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Preterm labour is a major cause of perinatal mortality and morbidity. However, during the past 40 years of clinical studies and despite the use of multiple therapeutic agents, the rate of preterm birth has not drastically declined. In 1991, it was estimated that in the US approximately 116,000 women admitted with acute episodes of preterm labour were treated each year with ritodrine, which is the first drug approved by the US FDA and still remains the standard therapy for treating preterm labour. Ritodrine (Yutopar( trade mark )) stimulates the beta(2)-adrenergic receptor throughout the body, causing an inhibitory action in different tissues that, among other side effects, also leads to an attenuation of uterine contractility. More recently, a new therapeutic agent, atosiban (Tractocile( trade mark )), a peptidic oxytocin receptor antagonist, has been introduced to the market. However, the use of the various pharmacological agents to treat preterm labour remains restricted, due to lack of uterine selectivity, low efficacy and potentially serious side effects for the mother or the foetus. Therefore, there is an urgent need to develop drugs with myometrial selectivity that would allow long-lasting inhibition of labour and prolong pregnancy up to a stage when good foetal maturation raises the chances of survival. One of the major obstacles hampering the development of new therapeutic agents is the marked inter-species difference in terms of preterm labour physiology, which complicates the preclinical evaluation of new candidate molecules in animal models of disease. In this review, the authors will provide a comprehensive update of past, current and new approaches for the management of preterm labour, including beta(2)-adrenergic agonists, calcium channel blockers, oxytocin antagonists, prostaglandin antagonists and other potential therapeutics. For each of the therapies used today, the review will cover the mechanism of action, benefit and adverse effects, and discuss the promise and potential benefits of new emerging therapeutic agents.

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The synthesis and vasopressin (AVP) antagonist activity of a novel series of n -aroyl-2,4,5,6-tetrahydropyrazolo [3,4- d ]thieno[3,2- b ]azepines

Cited by 23 publications

References 16 publications

Vasopressin antagonists

Vasopressin antagonists

The aquaretics in the treatment of hyponatremia

Preterm Labour: An Overview of Current and Emerging Therapeutics

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