371. Synthesis antimalarials. Part XLII. The preparation of guanylureas and biurets corresponding to “Paludrine” and related diguanides

Curd, F. H. S.; Davey, D. G.; Richardson, D. N.

doi:10.1039/jr9490001732

Cited by 18 publications

(10 citation statements)

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“…Most of the substances used in our work were prepared in these laboratories (Curd and Rose, 1946a;Curd, Davies, Owen, Rose, and Tuey, 1946;Curd, Richardson, and Rose, 1946;Curd and Rose, 1946b;Basford, Curd, and Rose, 1946;Curd and Rose, 1946c;Curd and Landquist, 1948;Curd, Landquist, and Rose, 1947). Others were obtained from Professor A. R. Todd (Hull, Lovell, Openshaw, Payman, and Todd, 1946;Hull, Lovell, Openshaw, and Todd, 1947).…”

Section: Methodsmentioning

confidence: 99%

Antimalarial Compounds as Antagonists of Adenosine

Madinaveitia

Raventós

1949

British Journal of Pharmacology and Chemotherapy

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The possible antagonism of the action of adenosine on some tissues by antimalarial drugs has been studied with the object of obtaining some information on the mode of action of this type of drug. METHODS Antagonism of adenosineThe following techniques were used in these experiments:(1) The isolated hen's caecum.-The action of adenosine on this tissue (Barsoum and Gaddurn, 1935) was studied before and after the addition to the bath -of known concentrations of antimalarials. Although it was possible to demonstrate an antagonism between these compounds and adenosine by this method, satisfactory results were not obtained because ofthe intense relaxation of the caecum produced by the antimalarial substances themselves.(2) The measurement of the duration of the auriculoventricular (a.v.) block produced by intravenous administration of adenosine in the anaesthetized guinea-pig (Drury and Szent-Gybrgyi, 1929 In each experiment a series of doses of adenosine from 0.1 to 0.3 mg./kg. was first administered in order to produce varying degrees of a.v. block. The cannula was then washed with the solution of antimalarial and the drug slowly infused by means of a motor-driven syringe which delivered the solution at the rate of 0.02 ml./min. This infusion was maintained for 30 min. after which the cannula was washed with adenosine solution and a second series of adenosine injections was administered in doses large enough to produce measurable heart blocks.The dose of antimalarial was calculated in mg./kg./min. and adjusted by varying the concentration according to the body-weight of each animal. At least 3 guinea-pigs were used for each dose level of antimalarial.This series was used mainly for the selection ofchemical types able to antagonize the action of adenosine.(b) In the second series the compounds were administered orally in a dosage regime similar to that used by Davey (1946) for the assessment of antimalarial activity against P. gallinaceum in chicks.Batches, usually of 6 guinea-pigs each, were used for each dose level of every compound tested. The animals received two doses daily for -31 days, a total of 7 doses. The drugs were administered in solution in water, or in fine suspensions when insoluble, by means of a stomach tube. After the 7th dose, the guinea-pigs were anaesthetized with pentobarbitone and a series of adenosine injections-was administered as described above.These experiments will be referred to as " chronic" later on.(c) Some experiments were carried out with heart-lung preparations of guinea-pigs. The method was essentially that described by Cruickshank (1945) for the rat; 25 ml. of heparinized guinea-pig's blood were used in the apparatus. The elastic peripheral resistance was adjusted to give a pressure of 80-100 mm. Hg in the aortic cannula; e.c.g. records were taken with leads placed in the superior vena cava and in the apex of the heart. Adenosine was injected into the venous cannula of the preparation.

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Section: Methodsmentioning

confidence: 99%

Antimalarial Compounds as Antagonists of Adenosine

Madinaveitia

Raventós

1949

British Journal of Pharmacology and Chemotherapy

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“…When the reaction temperature was reduced to 45 °C while the amounts of KOCN and AcOH were increased, the yields of ω-substituted biuret increased to 84 and 76%, respectively. For compound 1p, the influence of the electron-withdrawing group on the aniline is small, so that the strong nucleophilic ability of the amino group is maintained and the ω-substituted biuret compound can be obtained at relatively high temperatures (entries [14][15][16]. The reaction also proceeded well with naphthylamine 1q (entry 17).…”

Section: Paper Syn Thesismentioning

confidence: 99%

One-Pot Assembly towards ω-Substituted Arylbiurets from Aromatic Amines, Potassium Cyanate, and Glacial Acetic Acid

et al. 2017

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A novel, simple, and highly efficient method has been designed for the synthesis of ω-substituted arylbiurets in a one-pot reaction. The primary features of this protocol include readily available starting materials, an easy work-up procedure, and yields of 51 to 87%. ω-Substituted arylbiurets can be selectively prepared with an excess of potassium cyanate (KOCN). However, use of an excess of glacial acetic acid (AcOH) switches the reaction towards the formation of N-monosubstituted urea.

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“…(2) Acid hydrolysis of substituted biguanides: Some substituted biguanides arc more or less readily hydrolyzed and doaminated into the corresponding guanylureas in aqueous acid solution (26,78). Biguanides, more or less readily susceptible to such deamination by hydrolysis leading to the formation of corresponding guanylureas, can be represented by the general formula RC6H,NHC(=NH)NHC(=NH)NR'R" where R = II, Cl, or H2N02S (also with its hydrogen atoms partially or wholly replaced by CH3, C2H6, or Cell,); R' = H, CH3, or C2H6; and R" = CH,, C2H6, C8H7, C4H9, etc.…”

Section: Guanylureamentioning

confidence: 99%

“…Transformation Some substituted biguanides suffer more or less rapid hydrolysis in acid solution. A solution of paludrine, An-(p-chlorophenyl)-A7'E-isopropylbiguanide, in moderately strong hydrochloric acid, when kept for about a year, deposited crystals of chlorophenyl)-TV4-isopropylguanylurea (26). But much more rapid hydrolysis occurred in the case of N'-(p-sulfamoylphenyl) biguanide and some of its substituted derivatives (78).…”

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confidence: 99%

Complex Compounds of Biguanides and Guanylureas with Metallic Elements.

Ray¹

1961

Chem. Rev.

240

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371. Synthesis antimalarials. Part XLII. The preparation of guanylureas and biurets corresponding to “Paludrine” and related diguanides

Cited by 18 publications

References 0 publications

Antimalarial Compounds as Antagonists of Adenosine

Antimalarial Compounds as Antagonists of Adenosine

One-Pot Assembly towards ω-Substituted Arylbiurets from Aromatic Amines, Potassium Cyanate, and Glacial Acetic Acid

Complex Compounds of Biguanides and Guanylureas with Metallic Elements.

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371. Synthesis antimalarials. Part XLII. The preparation of guanylureas and biurets corresponding to “Paludrine” and related diguanides

Cited by 18 publications

References 0 publications

Antimalarial Compounds as Antagonists of Adenosine

Antimalarial Compounds as Antagonists of Adenosine

One-Pot Assembly towards ω-Substituted Arylbiurets from ­Aromatic Amines, Potassium Cyanate, and Glacial Acetic Acid

Complex Compounds of Biguanides and Guanylureas with Metallic Elements.

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One-Pot Assembly towards ω-Substituted Arylbiurets from Aromatic Amines, Potassium Cyanate, and Glacial Acetic Acid