Second-Generation KATP Channel Openers

Mannhold, Raimund; Leclerc, G.

doi:10.2174/138955705774575282

Cited by 7 publications

(2 citation statements)

References 51 publications

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“…This category of scaffolds was distributed throughout nature with a wide range of notable biological activities. On the other hand, the pyran moiety is still being used in the treatment of diverse ailments, like asthma, ischemia, hypertension, and urinary incontinence . Spiro all‐carbon quaternary compounds as valuable building blocks are present at the core of an array of natural products and drug candidates .…”

Section: Introductionmentioning

confidence: 99%

A convenient route toward one‐pot multicomponent synthesis of spirochromenes and pyranopyrazoles accelerated via quinolinic acid

Oudi

Tazeh

Hazeri

et al. 2019

J Chinese Chemical Soc

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In the present work, the catalytic activity of quinolinic acid (QUIN) was studied for the synthesis of spirochromene and pyranopyrazole derivatives from readily available materials. The salient features of these one‐pot multicomponent protocols are the clean reaction profile, easy isolation of products, no chromatographic separation techniques, high efficiency, short reaction time, and high yield of products plus using QUIN as a new, inexpensive, commercially available, and efficient organocatalyst.

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Section: Introductionmentioning

confidence: 99%

A convenient route toward one‐pot multicomponent synthesis of spirochromenes and pyranopyrazoles accelerated via quinolinic acid

Oudi

Tazeh

Hazeri

et al. 2019

J Chinese Chemical Soc

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“…In this study, the microelectrode array (MEA) was used to measure the field potentials (FPs) of rat peritoneal mast cells triggered by compound 48/80 alone as well as in the presence of different concentrations of two KCOs: SDZ PCO400 (SDZ), a benzopyran derivative, or P1060, a cyanoguanidine derivative. These KCOs were chosen because they are known to have an effect on adenosine triphosphate K + (K ATP ) channels (Fozard and Manley 2001) and because the activation of these channels has been implicated in immunological disorders (Chandy et al 2004), such as asthma (Mannhold and Leclerc 2005). The changes in FP as a result of the application of compound 48/80 in the absence or presence of KCO were compared with the changes in the amount of histamine released after the same drug treatment protocol with the aim of determining whether K + channel activation, and hence membrane hyperpolarization, affects the extent of peritoneal mast cell degranulation.…”

Section: Introductionmentioning

confidence: 99%

Modulatory action of potassium channel openers on field potential and histamine release from rat peritoneal mast cells

Yeung

Law

Sam

et al. 2009

Can. J. Physiol. Pharmacol.

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To determine whether changes in membrane potential affect the extent of mast cell degranulation, compound 48/80 was added to rat peritoneal mast cell suspensions in the absence or presence of potassium channel openers (KCOs). Changes were compared between the field potential (FP) and the amount of histamine released. The results demonstrated that (i) the onset and duration of FP, which reflects the hyperpolarizing nature of the response, increased as the concentration of compound 48/80 increased; (ii) both FP and the amount of histamine released increased as the concentration of compound 48/80 increased; (iii) although both KCOs (SDZ PCO400, a benzopyran derivative, and P1060, a cyanoguanidine derivative) potentiated compound 48/80-induced increases in FP and histamine release, without compound 48/80, they had no effect on either parameter; (iv) both glibenclamide and charybdotoxin significantly attenuated the compound 48/80-induced increase in FP; and (v) glibenclamide was able to attenuate the KCO-induced potentiation of FP. The results show that drugs presumably causing hyperpolarization can affect histamine release from rat peritoneal mast cells. The effect of KCOs on compound 48/80-induced response appears to be potentiation in nature rather than synergism. It is possible that KCO hyperpolarizes the cell membrane, enhances Ca2+ influx, and thus increases histamine release. As such, selective blockers of K+ channels may be useful for the treatment of immunological disorders.

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Nonequivalent Effects of Diverse LogP Algorithms in Three QSAR Studies

Melo

Ferreira

2009

QSAR Comb. Sci.

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Despite of the availability and facility of accessing several algorithms for calculation of LogP in QSA(P)R studies, articles typically do not describe the selection procedure for the method used. Therefore, three studies to verify the influence of different LogP algorithms on building QSAR models were performed. Two QSAR data sets from the literature (forty-two tricyclic phtalimide inhibitors of HIV-integrase and fourty-six TIBO derivatives inhibitors of HIV-reverse transcriptase) were used together with LogP calculated by thirteen algorithms, and several regression models were constructed and compared. A new QSAR study for 4,5-dihydroxypyrimidine carboxamides inhibitors of HIV-1 integrase was also performed. The explained and predicted variance, results from external validation, leave-N-out cross-validation and y-randomization test were analyzed for all models from the three data sets. Despite the same physicochemical meaning, LogPs calculated by distinct methods may show different levels of contribution to the model. This observation comes out from the comparison of validated models. These results indicate that the arbitrary choice of one specific algorithm for LogP calculation, as is usual in QSA(P)R studies , does not necessarily lead to the highest quality model for the analyzed data set.

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Second-Generation KATP Channel Openers

Abstract: This review discusses structural aspects of second-generation K(ATP) channel openers (KCOs), which exhibit improved tissue-selectivity. Their therapeutic profile is debated with main focus on cardiac ischemia, asthma, and urinary incontinence.

Cited by 7 publications

References 51 publications

A convenient route toward one‐pot multicomponent synthesis of spirochromenes and pyranopyrazoles accelerated via quinolinic acid

A convenient route toward one‐pot multicomponent synthesis of spirochromenes and pyranopyrazoles accelerated via quinolinic acid

Modulatory action of potassium channel openers on field potential and histamine release from rat peritoneal mast cells

Nonequivalent Effects of Diverse LogP Algorithms in Three QSAR Studies

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