Heterocyclic Syntheses on the Basis of Arylation Products of Unsaturated Compounds: X. 3-Aryl-2-chloropropanals as Reagents for the Synthesis of 2-Amino-1,3-thiazole Derivatives

Обушак, Н. Д.; Matiychuk, V. S.; Vasylyshin, R. Ya.; Ostapyuk, Yu. V.

doi:10.1023/b:rujo.0000034976.75646.85

Cited by 35 publications

(24 citation statements)

References 1 publication

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“…NS19504 was synthesized from readily available starting materials, as described by Obushak et al (2004). The compound is also commercially available and can be purchased from Enamine (Kiev, Ukraine).…”

Section: Methodsmentioning

confidence: 99%

NS19504: A Novel BK Channel Activator with Relaxing Effect on Bladder Smooth Muscle Spontaneous Phasic Contractions

Nausch

Rode

Jørgensen

et al. 2014

J Pharmacol Exp Ther

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Large-conductance Ca 21 -activated K 1 channels (BK, K Ca 1.1, MaxiK) are important regulators of urinary bladder function and may be an attractive therapeutic target in bladder disorders. In this study, we established a high-throughput fluorometric imaging plate reader-based screening assay for BK channel activators and identified a small-molecule positive modulator, NS19504 (5-[(4-bromophenyl)methyl]-1,3-thiazol-2-amine), which activated the BK channel with an EC 50 value of 11.0 6 1.4 mM. Hit validation was performed using high-throughput electrophysiology (QPatch), and further characterization was achieved in manual whole-cell and inside-out patch-clamp studies in human embryonic kidney 293 cells expressing hBK channels: NS19504 caused distinct activation from a concentration of 0.3 and 10 mM NS19504 left-shifted the voltage activation curve by 60 mV. Furthermore, whole-cell recording showed that NS19504 activated BK channels in native smooth muscle cells from guinea pig urinary bladder. In guinea pig urinary bladder strips, NS19504 (1 mM) reduced spontaneous phasic contractions, an effect that was significantly inhibited by the specific BK channel blocker iberiotoxin. In contrast, NS19504 (1 mM) only modestly inhibited nerve-evoked contractions and had no effect on contractions induced by a high K 1 concentration consistent with a K 1 channel-mediated action. Collectively, these results show that NS19504 is a positive modulator of BK channels and provide support for the role of BK channels in urinary bladder function. The pharmacologic profile of NS19504 indicates that this compound may have the potential to reduce nonvoiding contractions associated with spontaneous bladder overactivity while having a minimal effect on normal voiding.

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Section: Methodsmentioning

confidence: 99%

NS19504: A Novel BK Channel Activator with Relaxing Effect on Bladder Smooth Muscle Spontaneous Phasic Contractions

Nausch

Rode

Jørgensen

et al. 2014

J Pharmacol Exp Ther

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“…The extract was combined with the organic phase, dried over MgSO 4 and evaporated, and the residue was distilled under reduced pressure (bp 100°C/2 mm Hg, yield 35 %). 3-Phenyl-2-chloropropanal 2 reacted with thiourea in ethanol at refluxing and formed 2-amino-5-benzyl-1,3-thiazole 3 with a yield of 80 % [36].…”

Section: Experimental Synthesismentioning

confidence: 99%

Synthesis, structural characterization and thermal studies of a novel reagent 1-[(5-benzyl-1,3-thiazol-2-yl)diazenyl]naphthalene-2-ol

Tupys

Kalembkiewicz

Ostapiuk

et al. 2016

J Therm Anal Calorim

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A new thiazolylazo reagent 1-[(5-benzyl-1,3-thiazol-2-yl)diazenyl]naphthalene-2-ol has been synthesized via arylation of acrolein and further diazotization and diazocoupling with 2-naphthol. The chemical structure of the compound was confirmed by IR, NMR: 1 H, 13 C, COSY, HSQC and SALDI-MS spectral data. The DSC method was employed to determine the melting point and the enthalpy of fusion (T fus = 159.7°C and DH fus = 28.0 kJ mol -1 , respectively). Thermal stability and decomposition studies of the obtained azo dye were performed in air and nitrogen atmosphere using the TG technique. The evolved gases from the heated sample were registered on FTIR spectra. The decomposition of the azo dye in air atmosphere occurred in five consecutive stages. The pK a ionization constants of the substance were determined in ethanol-water mixture (1:1 v/v) by means of the spectroscopic method and were found to be equal to 0.41 for pK a1 and 9.59 for pK a2 . Using the spectrophotometric procedures, the methods for determination of trace amounts of toxic metallic ions with the new reagent were characterized and limits of detection were calculated.

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“…At the first stage acrolein was chloroarylated by diazonium salts in the presence of copper(II) chloride under Meerwein arylation conditions. Refluxing of 3-aryl-2-chloropropanals 2a-h and thiourea in ethanol gave 5-substituted 2-aminothiazoles 3a-h [15,16],…”

Section: Issn 2308-8303mentioning

confidence: 99%

“…Combine the extract with the organic phase, dry over MgSO 4 , evaporate, and distill the residue under reduced pressure. Compounds 2a, c-g were described earlier [15,16]. Heat the mixture of 0.8 g of thiourea and 0.01 Mol of aldehyde 2 in 10 ml of ethanol for 1.5-2 h under reflux.…”

Section: Experimental Partmentioning

confidence: 99%

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The synthesis and anticancer properties of 2-(4-amino-5-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(5-R-benzylthiazol-2-yl)-acetamides

Ostapiuk¹,

Matiychuk²,

Obushak³

2015

J. org. pharm. chem.

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Heterocyclic Syntheses on the Basis of Arylation Products of Unsaturated Compounds: X. 3-Aryl-2-chloropropanals as Reagents for the Synthesis of 2-Amino-1,3-thiazole Derivatives

Cited by 35 publications

References 1 publication

NS19504: A Novel BK Channel Activator with Relaxing Effect on Bladder Smooth Muscle Spontaneous Phasic Contractions

NS19504: A Novel BK Channel Activator with Relaxing Effect on Bladder Smooth Muscle Spontaneous Phasic Contractions

Synthesis, structural characterization and thermal studies of a novel reagent 1-[(5-benzyl-1,3-thiazol-2-yl)diazenyl]naphthalene-2-ol

The synthesis and anticancer properties of 2-(4-amino-5-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(5-R-benzylthiazol-2-yl)-acetamides

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