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Gastric H+/K+-ATPase inhibitors

Gastric H,K-ATPase inhibitors Potassium competitive acid blockers... [Pg.1031]

GABA, heterocyclic analogues, 22 (1985) 67 GABAa receptor ligands, 36 (1999) 169 Gas-liquid chromatography and mass spectrometry, 12 (1975) 1 Gastric H /K -ATPase inhibitors, 31 (1994) 233... [Pg.388]

As part of their study on gastric (H+/K+)-ATPase inhibitors, Kang et al. developed a simple and convenient synthetic approach to 1,2,3-trisubstituted pyrrolo[3,2-c]quinolines by means of Pd-catalyzed heteroannulation of 4-amino-3-iodoquinoline derivatives with internal alkynes [76]. The following scheme shows an example of a reaction using 4-arylamino-3-iodoquinoline derivative 180 with alkyne 181 to provide 1-arylpyrrolo [3,2-c]quinoline 182, illustrating the possibility of introducing diverse substituents to 1-arylpyrrolo[3,2-c]quinolines. In addition, a Pd-catalyzed domino hydroarylation/ cyclization process was reported to form substituted quinolines [77]. Thus, 3-arylquino-lines were prepared in 56-74% yield when 3,3-diethyl-l-phenyl-1-propyne and aryl iodide were refluxed in ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate [(bmim)BF4 ],in the presence of HCO2H, EtjN, and palladium catalyst. Meanwhile,... [Pg.535]

Figure 3.31 Use of the Mizoroki-Heck reaction in the synthesis of gastric H /K -ATPase inhibitors. Figure 3.31 Use of the Mizoroki-Heck reaction in the synthesis of gastric H /K -ATPase inhibitors.
Hartmann M, Bliesath H, Huber R, Koch H, Steinijans VW, Wurst W (1994) Simultaneous intake of antacids has no influence on the pharmacokinetcs of the gastric H K -ATPase inhibitor pantoprazole. Gut 35 (Suppl 4) A76... [Pg.168]

Proton Pump Inhibitors and Acid Pump Antagonists. Figure 2 Chemical mechanism of irreversible PPIs. PPIs are accumulated in acidic lumen and converted to active sulfenic acid and/or sulfenamide by acid catalysis. These active forms bind to extracytoplasmic cysteines of the gastric H.K-ATPase [3]. [Pg.1033]

Shin JM, Cho YM, Sachs G (2004) Chemistry of covalent inhibition of the gastric (H+,K+)-ATPase by proton pump inhibitors. J Am Chem Soc 126 7800-7811... [Pg.1035]

Shin JM, S achs G (2004) Differences in binding properties of two proton pump inhibitors on the gastric H+,K+-ATPase in vivo. Biochem Pharmacol 68 2117-2127... [Pg.1035]

In this chapter we will review the recent investigations of the structure of both the a and P subunit, and the function of gastric H,K-ATPase. We will proceed from a brief overview of the tissue distribution to a successive discussion of structure, kinetics, transport properties, lipid dependency, solubilization and reconstitution, and inhibitors of H,K-ATPase that may label functionally important domains of the enzyme. [Pg.28]

ATPase also catalyzed a passive Rb -Rb exchange, the rate of which was comparable to the rate of active Rb efflux. This suggested that the K-transporting step of H,K-ATPase is not severely limited by a K -occluded enzyme form, as was observed for Na,K-ATPase. Skrabanja et al. [164] also described the reconstitution of choleate solubilized H,K-ATPase into phosphatidylcholine-cholesterol liposomes. With the use of a pH electrode to measure the rate of H transport they observed not only an active transport, which is dependent on intravesicular K, but also a passive H exchange. This passive transport process, which exhibited a maximal rate of 5% of the active transport process, could be inhibited by vanadate and the specific inhibitor omeprazole, giving evidence that it is a function of gastric H,K-ATPase. The same authors demonstrated, by separation of non-incorporated H,K-ATPase from reconstituted H,K-ATPase on a sucrose gradient, that H,K-ATPase transports two protons and two ions per hydrolyzed ATP [112]. [Pg.46]

The search for specific inhibitors of gastric H,K-ATPase has a dual purpose. First, with the help of suitable inhibitors it is possible to get insight into the molecular mechanisms of H,K-ATPase, and second, a specific inhibitor might be clinically useful for inhibition of gastric acid secretion in anti-ulcer therapy. [Pg.46]

Lindberg et al. [169] proposed a mechanism of action for omeprazole, the inhibitor of the gastric H+/K+-ATPase, which is responsible for the gastric acid production and located in the secretory membranes of the parietal cell. Omeprazole itself is not an active inhibitor of this enzyme,... [Pg.250]

For the specific pharmacological assessment of inhibitors of gastric acid secretion, like H2-blockers, anticholinergics, H+/K+-ATPase inhibitors, this method reveals valid results with respect to the antisecretory potential of the candidate compound. Limitations of this methods with respect to safety pharmacological assessment of candidate compounds are (1) only parenteral administration of the candidate compound, preferentially i.v., is feasible and should be preferred, and (2) only antisecretory putative side effects can be investigated this method is of limited relevance to study secretory side effect potential of candidate compounds. [Pg.154]

Herling and Bickel (1986) showed that gastric acid secretion in stomach-lumen perfused rats can be stimulated in vivo on the subreceptor level by IBMX (phosphodiesterase inhibitor) and forskolin (non-receptor activation of the adenylate cyclase). H+/K+-ATPase inhibitors and H2-antagonists show, according to their different modes of action, also a different inhibitory profile in this assay. [Pg.155]

H2-receptor antagonists are quite effective in some peptic acid disorders (duodenal ulcers, gastric ulcers), whereas their effectiveness in others is less apparent (Zollinger-Ellison syndrome, gastrooesophageal reflux disease) [22]. For such conditions, prolonged and potent reduction of acid secretion caused by H /K -ATPase inhibitors is necessary and results in superiority of omeprazole over H2-receptor antagonists [25, 26]. [Pg.239]

The effect of gastric HVK -ATPase inhibitors on enzyme activity (ATP cleavage) can be studied in vitro with partly purified HVK -ATPase preparations [27]. This assay has been used more effectively to study the mechanism of action of H /K -ATPase inhibitors in detail than to study the structure-activity relationship of such inhibitors [28]. Since HVK -ATPase inhibitors of the omeprazole-type need acid activation and the enzyme assay should be performed at neutral pH values, a pre-incubation period at the lowest possible pH of about 6 was used to initiate the acidic conversion of the test compound into its active principle. This reflects more the chemical instability of the test compound at neutral pH values than its effect during conditions of much higher acidity within the secretory cannaliculus of the parietal cell during acid secretion. Many chemically labile inhibitors are therefore very active in this test system. However, they do not cause an inhibition in more complex test systems and, therefore, are without any practical usefulness [28]. [Pg.239]

Proton transport studies in intact gastric vesicles, which form a pH gradient similar to in vivo conditions, are more suitable for studying the mechanism of action, acid-conversion and structure-activity relationship of H /K -ATPase inhibitors [29-31]. [Pg.239]

Systematic synthesis was carried out by Smith Khne French to identify freely reversible, noncovalent inhibitors of gastric H /K -ATPase with a mode of action comparable with SCH 28080. It was expected that gastric HVK -ATPase inhibitors with a shorter duration of action could be of therapeutic interest [155, 156]. This research resulted in the selection of compound SK F 96067 [157] Figure 4.10). [Pg.256]


See other pages where Gastric H+/K+-ATPase inhibitors is mentioned: [Pg.25]    [Pg.88]    [Pg.396]    [Pg.233]    [Pg.155]    [Pg.161]    [Pg.25]    [Pg.88]    [Pg.396]    [Pg.233]    [Pg.155]    [Pg.161]    [Pg.40]    [Pg.47]    [Pg.47]    [Pg.49]    [Pg.220]    [Pg.22]    [Pg.612]    [Pg.130]    [Pg.79]    [Pg.158]    [Pg.159]    [Pg.159]    [Pg.68]    [Pg.238]    [Pg.240]    [Pg.249]    [Pg.255]   
See also in sourсe #XX -- [ Pg.31 , Pg.233 ]




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ATPase gastric

ATPase inhibitor

ATPase inhibitors, gastric

ATPases inhibitors

Gastric H+,K+-ATPase

H * -ATPase

H, K-ATPase

H, K-ATPase inhibitors

K , inhibitors

K+-ATPase

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