In our effort to identify potent purinergic P2Y(1) receptor antagonists as potent platelet aggregation inhibitors with enhanced metabolic stability, we developed an efficient route for the large-scale preparation of 2'-deoxy-C-nucleosides of pyrazolo[1,5-a]-1,3,5-triazine. The key strategic elements of this novel synthetic approach involved the following: (i) the use of a novel activating group, the N-methyl-N-phenylamino group, which was easily generated in high yield by treatment of the pyrazolo[1,5-a]-1,3,5-triazin-4-one (5) with phosphorus oxychloride and dimethylaniline under high pressure, (ii) a regio- and stereospecific palladium-mediated coupling reaction of the readily available unprotected glycal 1,4-anhydro-2-deoxy-D-erythro-pent-1-enitol (4b) and the 8-iodo derivative (16), and (iii) the stereoselective reduction of the ketone group of the furanosyl ring followed by the subsequent displacement of the N-methyl-N-phenylamino group upon treatment with methylamine. The beta configuration at the anomeric C-1' position of the glycal moieties was perfectly retained throughout this conversion. This procedure afforded 8-(2'-deoxy-beta-D-ribofuranosyl)-2-methyl-4-(N-methylamino)pyrazolo[1,5-a]-1,3,5-triazine (21) and 8-(2'-deoxy-beta-D-xylofuranosyl)-2-methyl-4-(N-methylamino)pyrazolo[1,5-a]-1,3,5-triazine (24) with an overall yield of 50% and 39%, respectively. Finally, the conversion of nucleosides 21 and 24 to the pyrazolotriazine C-nucleotides 3',5'-bisphosphate 2 and 3',5'-cyclophosphate 26 is also described herein and represents the first reported nucleotide derivatives within the pyrazolo[1,5-a]-1,3,5-triazine series. Preliminary biological testing has shown that compound 2 strongly inhibits ADP-induced human platelet aggregation and shape change and possesses significant efficacies 30 min after injection in rat, highlighting a strong P2Y(1)-receptor antagonist activity in vitro combined with a prolonged duration of action in vivo.

Carbon nitride nanostructures have been produced by the arc-discharge technique and analyzed by mass spectrometry. A series of structured peaks in the region of masses from 480 up to 600 suggests the existence of heterofullerenes C(n-x)Nx(40 < or = n < or = 50). The structure and stability of these small fullerenes were theoretically investigated by quantum chemical calculations. The obtained heats of formation indicate that C(n) molecules stabilize upon nitrogen substitution. Two C(n-x)Nx cages are quite stable, with heats of formation per atom approaching that of C60. These molecules could be the seeds of onion-like structures seen in CN materials [Phys. Rev. Lett. 87, 225503 (2001)]].

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Triazine derivatives Triazine derivatives R 0655A General Approach Toward the Synthesis of 8-Acylamidopyrazolo[1,5-a]-1,3,5-triazines. -The diamino-pyrazolotriazine (III) is used as starting material for the preparation of various 8-acrylamido-pyrazolotriazines (VII). These are obtained by a tandem procedure involving diacylation of the amino moieties followed by displacement of the N-methyl-N-phenylamino leaving group at C-4 with amines. This displacement also occurs with the dinitro derivative (II), but not with (III). -(RABOISSON*, P.; SCHULTZ, D.; LUGNIER, C.; MATHIEU, R.; BOURGUIGNON, J.-J.; Tetrahedron Lett. 44 (2003) 4, 703-705; Lab. Pharmacochim. Commun. Cell., Fac. Pharm., CNRS, Univ. Louis Pasteur, F-67401 Illkirch, Fr.; Eng.) -Roy 18-141

Triazine derivativesTriazine derivatives R 0655 Efficient Synthesis of 8-Substituted Pyrazolo[1,5-a]-1,3,5-triazines by Regioselective Acylation. -A first general synthesis of the title compounds (III) and (IX) is achieved using SnCl 4 without solvent. -(RABOISSON*, P.; SCHULTZ, D.; LUGNIER, C.; BOURGUIGNON, J.-J.; Tetrahedron Lett. 43 (2002) 52, 9501-9503; Lab. Pharmacochim. Commun. Cell., Fac. Pharm., CNRS, Univ. Louis Pasteur, F-67401 Illkirch, Fr.; Eng.) -Mais 12-152