1,2,5-Thiadizole 1-oxide and 1,1-dioxide derivatives. A new class of potent histamine H2-receptor antagonists

Algieri, Aldo A.; Luke, G. M.; Standridge, R. T.; Brown, Myron; Partyka, R. A.; Crenshaw, R. R.

doi:10.1021/jm00345a003

Cited by 53 publications

(23 citation statements)

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“…31 The measured phenyl-heterocycle dihedral angles for the sp 3 32 there is no measurable steric effect caused by the length of the hydrocarbon chain. 31 The measured phenyl-heterocycle dihedral angles for the sp 3 32 there is no measurable steric effect caused by the length of the hydrocarbon chain.…”

Section: Discussion Monoadditionmentioning

confidence: 98%

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Electrochemical and spectroscopic study of the addition of several nucleophiles to 1,2,5-thiadiazole 1,1-dioxide derivatives

Aimone

Caram

Mirífico³

et al. 2000

J. Phys. Org. Chem.

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The nucleophilic addition reactions of several alcohols and 1‐propanethiol to a CN double bond of 3,4‐disubstituted derivatives of 1,2,5‐thiadiazole 1,1‐dioxide were studied in acetonitrile solution. The substrates used were 3,4‐diphenyl (1a), 3‐methyl‐4‐phenyl (1b), phenanthro[9,10‐c] (1c) and acenaphtho[1,2‐c]‐1,2,5‐thiadiazole 1,1‐dioxide (1d), 3,4‐diphenyl‐1,2,5‐thiadiazoline 1,1‐dioxide (2a) and 4‐ethoxy‐5‐methyl‐3,4‐diphenyl‐1,2,5‐thiadiazoline 1,1‐dioxide (2b). Spectroscopically (UV–VIS) and electrochemically (cyclic voltammetry) measured equilibrium constants at 25.0 °C are presented and discussed for the reaction of 1a and 1b with alcohols (methanol, n‐propanol, n‐butanol, isobutanol, 2‐propanol, sec‐butanol, tert‐butanol, ethylene glycol, allyl alcohol and 2‐phenylethanol). A reaction of 1‐propanethiol with 1c was observed, but the alcohols did not react with 1c, 1d or the thiadiazolines (2a, 2b). The effect of the solvent on the equilibrium constant of the 1a–ethanol system was measured using, besides acetonitrile, propylene carbonate, N,N‐dimethylformamide, N,N‐dimethylacetamide, dimethyl sulfoxide and tert‐butanol. The results were correlated with an empirical H‐bond acceptor solvent parameter. Previously unreported spectroscopic (UV–VIS, IR, 1H and 13C NMR) data for some of the compounds studied are also provided. Copyright © 2000 John Wiley & Sons, Ltd.

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Section: Discussion Monoadditionmentioning

confidence: 98%

“…(3)] of the relative intensity of these peaks and the voltage sweep rate (v) can be used to calculate the equilibrium constant: A function [Eqn.…”

Section: Experimental Measurementsmentioning

confidence: 99%

Electrochemical and spectroscopic study of the addition of several nucleophiles to 1,2,5-thiadiazole 1,1-dioxide derivatives

Aimone

Caram

Mirífico³

et al. 2000

J. Phys. Org. Chem.

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“…A H2-receptor antagonist with the imidazole group in its structure, cimeti dine, was the first drug to be used for the clini cal treatment of ulcer patients. Since then, H2-receptor antagonists, ranitidine (8) and famotidine (9), which do not have the imida zole group in their structure have been used, and a series of diaminothiadiazole oxide and dioxides (10,11) have been reported. Recent ly, new H2-receptor antagonists, L-643,441, lamtidine (AH 22216), loxitidine (AH 23844) and BMY-25368 (SK&F 94482), which contain a piperidinomethylphenyl moiety in their structure have been reported (6,7,12).…”

Section: Abstract 3-amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-mentioning

confidence: 99%

Time-Dependent Interaction of a New H2-Receptor Antagonist, IT-066, with the Receptor in the Atria of Guinea Pig

Muramatsu

Hirose-Kijima

Aihara

et al. 1991

Japanese Journal of Pharmacology

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3-Amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2-butenylamino] 3-cyclobutene-1,2-dione hydrochloride (IT-066) showed a highly potent and long last ing H2-receptor blocking action in guinea pig atria. The inhibitory effect of IT-066 on the histamine-induced positive chronotropic response increased concentration and time-dependently. A short period of treatment with IT-066 shifted the concentration response curve of histamine to the right in parallel, without decreasing the maximal response to histamine. With prolongation of the treatment, the concentration-response curve shifted further to the right with time-dependent suppression of the maximal re sponse to histamine. The inhibitory effect of IT-066 was irreversible. The dissociation constant for histamine (KA) was not changed by prolongation of the time of incuba tion with IT-066. The dissociation constant for IT-066 (KB) was decreased with the prolongation of the treatment. Kinetic analysis of the time-dependent inhibition showed a two-step reaction: the first was reversible and the second was irreversible. Preincubation of the atria with ranitidine, however, protected the H2-receptor from the apparently irreversible antagonism of IT-066. These results suggest that IT-066 has a time-dependent and irreversible interaction with the H2-receptor and that the in teraction may be responsible for the potent and long lasting H2-receptor blocking ac tion of IT-066.The discovery of burimamide, a prototype H2-receptor antagonist (1), has prompted in tensive investigations to clarify the physiologi cal and pharmacological involvement of his tamine in the regulation of gastric acid secre tion (2-4). These have included a search for more useful H2-receptor antagonists for the treatment of peptic ulcer with gastric hyper acidity (5-7). A H2-receptor antagonist with the imidazole group in its structure, cimeti dine, was the first drug to be used for the clini cal treatment of ulcer patients. Since then, H2-receptor antagonists, ranitidine (8) and famotidine (9), which do not have the imida zole group in their structure have been used, and a series of diaminothiadiazole oxide and dioxides (10, 11) have been reported. Recent ly, new H2-receptor antagonists, L-643,441, lamtidine (AH 22216), loxitidine (AH 23844) and BMY-25368 (SK&F 94482), which contain a piperidinomethylphenyl moiety in their structure have been reported (6,7,12). These compounds produced unsurmountable antago nism in guinea pig atria and showed very po tent and long lasting inhibition of gastric acid secretion. The mechanism, however, has not

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“…Analogous results have been obtained by Algieri etal. [14] in the same preparation with compounds structurally related to lamtidine containing the 3,4-diamino-1,2,5,-thiadiazole S-oxide, a polar substructure whose physicochemical properties are similar to those of diaminofurazan. Therefore the unsurmountable antagonism in vitro and the prolonged time course of antisecretory activity in vivo of lamtidine may be related to the triazole moiety.…”

Section: Discussionmentioning

confidence: 99%

Histamine H2-receptor blocking activity of ranitidine and lamtidine analogues containing aminomethyl-substituted aliphatic systems

Orsetti

1988

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The possibility that the aromatic component in the classical H2-antagonists might not be essential for histamine H2-receptor blockade has been investigated. In the ranitidine series the removal of the furan ring is accompanied by a drastic decrease in H2-blocking activity, but not by its disappearance (compound HB5:KB on guinea pig isolated atria 31.6 microM) whereas in the lamtidine analogues the substitution of the phenyl moiety with the more reduced pi-bonded CH3-C = N-area generates a compound whose activity is comparable to that of cimetidine (KB on atria 1.12 microM; ID50 in the lumen-perfused stomach of the anaesthetized rat 3.61 mumol/kg i.v.). The results also indicate that the diaminofurazan group confers high affinity at the histamine H2-receptor. It is concluded that the aromatic portion of H2-antagonists related to ranitidine and lamtidine is not a minimal requisite for activity when an appropriate polar group is used as an "urea equivalent" moiety.

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1,2,5-Thiadizole 1-oxide and 1,1-dioxide derivatives. A new class of potent histamine H2-receptor antagonists

Cited by 53 publications

References 0 publications

Electrochemical and spectroscopic study of the addition of several nucleophiles to 1,2,5-thiadiazole 1,1-dioxide derivatives

Electrochemical and spectroscopic study of the addition of several nucleophiles to 1,2,5-thiadiazole 1,1-dioxide derivatives

Time-Dependent Interaction of a New H2-Receptor Antagonist, IT-066, with the Receptor in the Atria of Guinea Pig

Histamine H2-receptor blocking activity of ranitidine and lamtidine analogues containing aminomethyl-substituted aliphatic systems

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