1,721,010 research outputs found
NEW 1,2,3-TRIAZOLO[4,5-E]1,2,3-TRIAZOLO[4,3-C]PYRIMIDINE DERIVATIVES.II
No full textThe 7-chloro-3-(2-chlorobenzyl)- and 7-chloro-3-(2-fluorobenzyl)-1,2,3-triazolo[4,5-d]pyrimidines (1 and 4), by nucleophilic replacement with some hydrazides, gave the corresponding 7-hydrazidoderivatives (2a-e and 5a-e). These, by heating in Dowtherm, underwent an intramolecular cyclization to form the new tricyclic 7-substituted-3-(2-chlorobenzyl)- and 3-(2-fluorobenzyl)-1,2,3-triazolo[4,5-e]1,2,4-triazolo[4,3-c]pyrimidines (3a-d and 6a-d). The 7-hydrazino-3-(2-chlorobenzyl)- and 7-hydrazino-3-(2-fluorobenzyl)-triazolo-pyrimidines (9a and 9b) were also prepared via the corresponding mercapto (7a and 7b) and thiomethyl (8a and 8b) derivatives
1,2,3-TRIAZOLO[4,5-e]-1,2,4-TRIAZOLO[3,4-c]PYRIMIDINES
No full textSome new 1,2,3-triazolo[4,5-e]-1,2,4-triazolo[3,4-c]pyrimidines were prepared starting from the corresponding 1,2,3-triazolo[4,5-d]pyrimidines via the formation of the 1,2,4-triazole ring. Thus suitable hydrazino derivatives 6 were condensed with triethyl orthoformate, triethyl orthoacetate and triethyl orthobenzoate to give the expected tricyclic derivatives 7, 8 and 9. Intramolecular cyclization of the ethoxycarbonylhydrazino derivatives 10 gave the tricyclic compounds 11 bearing an hydroxyl group in the 3 position. The v-triazolo-s-triazolopyrimidine derivatives were tested towards the A1 and A(2A) adenosine receptors in binding assays, but they did not show any receptor affinity
NEW 2-(2'-PHENYL-9'-AZAPURIN-6'-YLAMINO)-CARBOXYLIC ACID METHYLESTERS AS LIGANDS FOR A1 ADENOSINE RECEPTORS
No full textSynthesis of a series of new 2-phenyl-9-benzyl-8-azaadenines bearing on N6 an alkyl or aralkyl chain having a carbonyloxymethyl group on the carbon bound to N6 were reported. The ester group could assure to the molecule a better water-solubility than the 8-azaadenines 2, 6 and 9 substituted with lipophilic groups synthesised in the past. Compounds synthesised demonstrated only little capability of binding A1 adenosine receptors
CHARACTERIZATION AND PRELIMINARY EMPLOYMENT OF 1-, 2- AND 3-METHYL-5-PHENYL-7-CHLORO-1,2,3-TRIAZOLO[4,5-D]PYRIMIDINE
No full textThis paper reports synthesis and characterization, by spectroscopic methods, of three new N-methyl-5-phenyl-7-chloro-1,2,3-triazolo[4,5-d]pyrimidine isomers 3a, 3b and 3c. For comparison purpose the 3-benzyl-5-phenyl-7-chloro-1,2,3-triazolo[4,5-d]pyrimidine (7) was also prepared. Starting from the isomer mixture 3a–c and the chloroderivative 7, by nucleophilic substitution reaction with ethyl carbazate and subsequent intramolecular cyclization, the new tricyclic derivatives 5a–c and 9 were prepared and tested towards the benzodiazepine and adenosine A1 and A2A receptors
NEW 1,2,3-TRIAZOLO[1,5-a]QUINOXALINES: SYNTHESIS AND BINDING TO BENZODIAZEPINE AND ADENOSINE RECEPTORS. II
No full textOn pursuing research about 1,2,3-triazolo[1,5-a]quinoxalines. in this paper we report synthesis and binding assays toward the benzodiazepine and A(1) and A(2A) adenosine receptors. of a new series of derivatives, bearing some structural changes (introduction of fluorine and trifluoromethyl in the seventh position, amino substituents in the fourth position, benzyl group in the fifth position and aroyl substituents in the third position). The biological tests have shown that only the 7-fluorosubstituted compounds 3a and 4a and the N-benzyl derivative 7 have a good affinity toward the benzodiazepine receptors, while only the 7-trifluoromethyl substituted compound 3b presents a moderate affinity with low selectivity toward the A, adenosine receptors. The other structural modifications strongly decreased biological activity. (C) 2002 Published by Editions scientifiques et medicales Elsevier SAS
TRIAZOLYLBENZIMIDAZOLTHIONES AND DERIVATIVES OF THE NEW 1,2,3-TRIAZOLO[1,5-A][1,3,5]BENZOTRIAZEPINE HETEROCYCLE
No full textFour new triazolylbenzimidazolthione derivatives (2a-d), analogous to triazolylbenzimidazolone derivatives previously tested as activators of the BKCa potassium channels, were prepared and, assayed without success. Some derivatives of a new tricyclic nitrogen heterocycle, 1,2,3-triazolo[1,5-a][1,3,5]benzotriazepine, bearing a carboxamido group in the 3 position, other substituents in the 8 position and a carbonyl (5a-d) or thione (6a-c) or methylthio (7a-c) function in the 5 position were synthesised.,The nucleophilic displacement of the methylthio substituent with morpholine or cyclopentylamine provided the 5-amino-substituted tricyclic derivatives 8a-d. Starting from the 1-(2-nitrophenyl)-4-cyano-5-aniino-1,2,3-triazole (9), the 3-cyano-triazolobenzotriazepin-5-one derivative 12 was also obtained. The majority of the new compounds were tested towards the BKCa potassium channels, the benzodiazepine and adenosine A(1) and A(2A) receptors, but no remarkable activity was detected
NEW N6-OR N(9)-HYDROXYALKYL SUBSTITUTED 8-AZAADENINES OR ADENINES AS AFFECTIVE A1 ADENOSINE RECEPTOR LIGANDS
No full textIn this paper we describe synthesis and biological assays of some A, ligands more water-soluble than the effective, but very lipophilic. 8-azaadenines and adenines discovered in the past and obtained introducing on N-6 or N(9) substituent a hydroxy group. Five of the new N-6-hydroxyalkyl- and N-6-hydroxycycloalkyl-2-phenyl-9-benzyl-8-azaadenines showed very high affinity (Ki < 40 nM) and selectivity for A, adenosine receptors. Among the 2-phenyl-9-(2-hydroxy-3-alkyl)-8-azaadenines or adenines prepared, the compounds with the higher A, affinity and selectivity resulted 2-phenyl-9-(2-hydroxy-3-propyl)-N-6-cyclopentyl- and cyclohexyl-8-azaadeninewith Ki 2.2 +/- 0.2 nM and 2.8 +/- 0.3 nM respectively. From the point of view of water-solubility, 2-phenyl-9-(2-hydroxy-3-propyl)-8-azaadenine was the most interesting compound, having a CLogP of 1.066991 and a water-solubility of 1.2 mg in L-1. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved
2-ALKYLOXYALKYLTHIOHYPOXANTHINES AS NEW POTENT INHIBITORS OF XANTHINE OXIDASE
No full textThe title compounds were prepared and tested as xanthine oxidase (XO) inhibitors. Results evidenced that potency was related to the position of the oxygen atom in the 2-linear chain and that it grew with distance from the sulfur atom until it became equipotent to 2-n-hexylthiohypoxanthine. Enzymatic oxidation on C(2) occurred in the 8-alkylthiohypoxanthines. On the contrary, oxidation on C(8) did not occur in the 2-alkythioderivatives, demonstrating that the chain forced these molecules to form a complex with molybdenum(VI) involving only the N(3) and N(9) nitrogen atoms
Preparation of New N6,9-disubstituted-2-phenyladenines and corresèponding 8-azaadenines. A feasibility study for application to solid-phase synthesis
No full textA suitably substituted pyrimidine 1 was converted to a number of title compounds. Nucleophilic substitution involving the chlorine atoms in 1 by treatment with phenylmethanethiol yielded 2 or 3, depending on the reaction temperature. Treatment of 3 with an amine afforded 6-phenylmethanesulfanyl-N4-substituted-2-phenyl-pyrimidine-4,5-diamines 4-7. These pyrimidines were converted into 2-phenylpurines 8-11 and 2-phenyl-8-azapurines 12-14, by treatment with triethyl orthoformate in the presence of hydrochloric acid (or acetic anhydride), or with potassium nitrite and acetic acid respectively. The thioether function on C(6) was then converted into a sulfonyl group by oxidation with m-chloroperoxybenzoic acid affording purines 15-18 and their 8-azaanalogs 19-21; these compounds, as crude products, were treated with an amine to yield the corresponding adenines 22-25 or 8-azaadenines 26-31. All reactions were performed under conditions compatible with the possible use of a thiomethyl resin in place of phenylmethanethiol to bind the pyrimidine ring of 1 to a solid phase
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