556
G. Biagi et al. / Il Farmaco 58 (2003) 551ꢀ556
/
2H), 1.26 (t, 3H). Mass (m/z): 389 (Mꢂ), 91 (base).
Anal. (C20H19N7O2): C, H, N.
[9] J.E.R. Borges, F. Fernandez, X. Garzia, A.R. Hergueta, C.
Lopez, G. Andrei, R. Snoeck, M. Witvrounw, J. Balzarini, E. De
Clercq, Novel carbocyclic nucleosides containing a cyclobutyl
ring. Guanosine and adenosine analogs, Nucleos. Nucleot. 17
3.7. 3-Benzyl-5-phenyl-7-hydroxy-1,2,3-triazolo[4,5-
e]1,2,4-triazolo[3,4-c]pyrimidine (9)
(1998) 1237ꢀ1253.
/
[10] (a) H.-D. Kummer, Phosphodiesterase inhibitors for treatment of
bladder disorders, German Patent 19,529,102 (1997).;
(b) H.-D. Kummer, Phosphodiesterase inhibitors for treatment of
bladder disorders, Chem. Abstr. 126 (1997) 152808.
A solution of 0.200 g (0.50 mmol) of 8 in 3 ml of
Dowtherm was heated under reflux (:230 8C) for 2.5
/
[11] (a) M. Grifantini, P. Franchetti, L. Cappellacci, P. La Colla, A.G.
Loi, G. Piras, Preparation of purine and 8-azapurine derivatives
for treatment of acquired immune deficiency syndrome, World
Patent 9,609,307 (1996).;
hours. After cooling the reaction mixture was diluted
with petroleum ether and stirred for 30 min. The
precipitated solid, consisting of the title compound,
was crystallized from water: 0.134 g, yield: 77%, m.p.
(b) M. Grifantini, P. Franchetti, L. Cappellacci, P. La Colla, A.G.
Loi, G. Piras, Preparation of purine and 8-azapurine derivatives
for treatment of acquired immune deficiency syndrome, Chem.
Abstr. 125 (1997) 87111.
185ꢀ
/
189 8C. 1H NMR (DMSO-d6): d 12.6 (broad, OH),
7.76ꢀ
/
7.20 (m, 10H), 5.83 (s, 2H). Mass (m/z): 343
(Mꢂ), 91 (base). Anal. (C18H13N7O): C, H, N.
[12] L. Betti, G. Biagi, G. Giannaccini, I. Giorgi, O. Livi, A.
Lucacchini, C. Manera, V. Scartoni, Novel 3-aralkyl-7-aminosub-
stituted 1,2,3-triazolo[4,5-d]pyrimidines with high affinity towards
A1 adenosine receptors, Eur. J. Med. Chem. 34 (1999) 867ꢀ875.
/
References
[13] G. Biagi, I. Giorgi, O. Livi, V. Scartoni, A. Lucacchini, N(9)-
substituted2-phenyl-N(6)-Benzyl-8-azaadenines: A1 adenosine re-
ceptor affinity. A comparison with the corresponding N(6)-
substituted 2-phenyl-N(9)-benzyl-8-azaadenines, Farmaco 51
[1] T. Higashino, T. Katori, H. Kawaraya, E. Hayashi, Triazolo[4,5-
d]pyrimidines. V. The nucleophilic substitution of 7-chloro and 7-
(p-tolylsulfonyl)-3-phenyl-3H-1,2,3-triazolo[4,5-d]pyrimidines,
(1996) 395ꢀ399.
/
Chem. Pharm. Bull. 28 (1980) 337ꢀ
/
343.
[14] G. Biagi, I. Giorgi, O. Livi, V. Scartoni, Xanthine oxidase (XO).
Synthesis of 4(5)-carboxyamido-5(4)-aminoalkanoyl)amino-1,2,3-
triazoles and their cyclization to 8-azahypoxanthines. Evaluation
[2] G. Biagi, I. Giorgi, O. Livi, V. Scartoni, A. Lucacchini, N(6)-
Substituted 2-phenyl-9-benzyl-8-azaadenines. Affinity for adeno-
sine A1 and A2 receptors. A comparison with 2-N-butyl analo-
for inhibition of XO, Farmaco 51 (1996) 301ꢀ303.
/
gous derivatives, Farmaco 49 (1994) 187ꢀ
/
191.
[15] G. Biagi, I. Giorgi, O. Livi, V. Scartoni, C. Breschi, C. Martini, R.
Scatizzi, N(6) or N(9) substituted 2-phenyl-8-azaadenines: affinity
[3] J.L. Kelley, R.G. Davis, E.W. McLean, R.C. Glen, F.E. Soroko,
B.R. Cooper, Synthesis and anticonvulsant activity of N-benzyl-
pyrrolo[2,3-d]-, pyrazolo[3,4-d]-, and triazolo[4,5-d]pyrimidines:
imidazole ring-modified analogues of 9-(2-fluorobenzyl)-6-
for A1 adenosine receptors. VII, Farmaco 50 (1995) 659ꢀ667.
/
[16] G. Biagi, I. Giorgi, O. Livi, V. Scartoni, I. Tonetti, L. Costantino,
Xanthine oxidase (XO). 4(5)-aminosubstituted-5(4)-carboxya-
(methylamino)-9H-purine, J. Med. Chem. 38 (1995) 3884ꢀ
/
3888.
mido-1H-1,2,3-triazoles:
a
new class of monocyclic triazole
264.
[4] L. Betti, G. Biagi, G. Giannaccini, I. Giorgi, O. Livi, A.
Lucacchini, C. Manera, V. Scartoni, Novel 3-aralkyl-7-aminosub-
stituted 1,2,3-triazolo[4,5-d]pyrimidines with high affinity towards
inhibitors, Farmaco 50 (1995) 257ꢀ
[17] B.J. Broughton, P. Chaplen, P. Knowles, E. Lunt, S.M. Marshall,
D.L. Pain, K.R.H. Wooldridge, Antiallergic activity of 2-phenyl-
/
A1 adenosine receptors, J. Med. Chem. 41 (1998) 668ꢀ
/673.
8-azapurin-6-ones, J. Med. Chem. 18 (1975) 1117ꢀ1122.
/
[5] G. Biagi, I. Giorgi, O. Livi, C. Manera, V. Scartoni, 1,2,3-
Triazolo[4,5-e]-1,2,4-triazolo[3,4-c]pyrimidines, J. Heterocyclic
[18] O. Livi, G. Biagi, M. Ferretti, A. Lucacchini, P.L. Barili,
Synthesis and in vitro antiinflammatory activity of 4-phenyl-
Chem. 36 (1999) 1195ꢀ
/1198.
1,2,3-triazole derivatives, Eur. J. Med. Chem. 18 (1983) 471ꢀ475.
/
[6] G. Biagi, I. Giorgi, F. Pacchini, O. Livi, V. Scartoni, New 2-(2?-
phenyl-azapurin-6?-ylamino)-carboxylic acid methylesters as li-
[19] G. Biagi, O. Livi, A. Da Settimo, A. Lucacchini, M.R. Mazzoni,
P.L. Barili, 4-(4-Phenylsubstituted)-1,2,3-triazolacetic acid deri-
vatives in vitro inhibitors of prostaglandin synthesis, Farmaco 40
gands for A1 adenosine receptors, Farmaco 56 (2001) 929ꢀ932.
/
[7] C. Adrie, A. Holzmann, W.M. Hirani, W.M. Zapol, W.E.
Hurford, Effects of intravenous zaprinast and inhaled nitric oxide
on pulmonary hemodynamics and gas exchange in an ovine model
of acute respiratory distress syndrome, Anesthesiology 93 (2000)
(1985) 73ꢀ
[20] F.R. Benson, The High Nitrogen Compounds, Wiley, New York,
1984, pp. 293ꢀ315.
[21] P.L. Barili, G. Biagi, O. Livi, V. Scartoni, A facile one pot
synthesis of 2,9-disubstituted 8-azapurin-6-ones (3,5-disubstituted
7-hydroxy-3H-1,2,3-triazolo[4,5-d]pyrimidines), J. Heterocyclic
/
85.
/
422ꢀ430.
/
[8] (a) G.A. Piazza, R. Pamukcu, Preparation of phenyl purinone
derivatives for the treatment of precancerous lesions, US Patent
6,200,980 (2001).;
Chem. 22 (1985) 1607ꢀ1609.
/
[22] L. Bertelli, G. Biagi, I. Giorgi, C. Manera, O. Livi, V. Scartoni, L.
Betti, G. Giannaccini, L. Trincavelli, P.L. Barili, 1,2,3-Tria-
zolo[1,5-a]quinoxalines: synthesis and binding to benzodiazepine
(b) G.A. Piazza, R. Pamukcu, Preparation of phenyl purinone
derivatives for the treatment of precancerous lesions, Chem.
Abstr. 134 (2001) 222726.
and adenosine receptors, Eur. J. Med. Chem. 33 (1998) 113ꢀ122.
/