Novel arylpyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides as inhibitors of platelet aggregation. 1. Synthesis and pharmacological evaluation

Journal of Medicinal Chemistry

Volumn 42, Issue 10, 1999, Pages 1698-1704

  Campillo, Nuria ^a   García, Concepción ^a   Goya, Pilar ^a   Páez, Juan A ^a   Carrasco, Emilio ^b   Grau, Manuel ^b  

^a INSTITUTO DE QUÍMICA MÉDICA   (Spain)

^b SA Research Centre ^*  (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

15 HYDROXY 11ALPHA,9ALPHA EPOXYMETHANOPROSTA 5,13 DIENOIC ACID; ADENOSINE DIPHOSPHATE; ANTITHROMBOCYTIC AGENT; ARACHIDONIC ACID; ARYLPYRAZINO[2,3 C][1,2,6]THIADIAZINE 2,2 DIOXIDE; COLLAGEN; UNCLASSIFIED DRUG;

ANIMAL CELL; ARACHIDONIC ACID METABOLISM; ARTICLE; DRUG EFFECT; DRUG MECHANISM; DRUG POTENCY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; MALE; NONHUMAN; RABBIT; RAT; REACTION ANALYSIS; STRUCTURE ACTIVITY RELATION; THROMBOCYTE AGGREGATION INHIBITION;

ANIMALS; CYCLIC S-OXIDES; HUMANS; MALE; PLATELET AGGREGATION INHIBITORS; RABBITS; RATS; RATS, WISTAR; STRUCTURE-ACTIVITY RELATIONSHIP; THIADIAZINES;

EID: 0033587025     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm981103j     Document Type: Article

References (15)

1. Majerus, W.; Broza, G. J.; Miletich, J. P.; Tollesfsen D. M. Anticoagulant, Thrombolytic and Antiplatelet Drugs. In The Goodman Gilman's the Pharmacological Basis of Therapeutics; Goodman, L. S., Gilman, A. G., Hardman, J. G., Limbird, L. E., Eds., McGraw-Hill: New York, 1996: pp 1341-1359.
2. Prous, J. R. Antithrombotic Drugs. Agents Affecting Blood Coagulation. Anticoagulants. Agents Affecting Blood Coagulation. Antiplatelet Therapy in The Year's Drugs News. In Therapeutic Targets; Prous, J. R., Ed.; Prous Science, 1995; pp 257-265.
3. Scahfer, A. I. Antiplatet therapy. Am. J. Med. 1996, 101 (2), 199-209.
4. Armstrong, R. A.; Wilson, N. H. Aspects of The Thromboxane Receptor System. Gen. Pharmacol. 1995, 26 (3), 463-472.
5. Verstraete, M. Thromboxane Synthase Inhibition, Thromboxane/Endoperoxide Receptor Blockade and Molecules With Dual Property. Drugs Today 1993, 29 (3), 221-232.
6. Goya, P.; Páez, J. A.; Pfleiderer, W. Pyrazino[2,3-c][1,2,6]-thiadiazine 2,2-Dioxides. Sulfur Dioxide Analogues of Pteridines. J. Heterocycl. Chem. 1984, 21, 861-864.
7. Goya, P.; Herrero, A.; Jimeno, M. L.; Ochoa, C.; Páez, J. A. Tautomerism in Pyrazino[2,3-c][1,2,6]thiadiazine 2,2-Dioxides. Heterocycles 1988, 27, 2201-2209.
8. Alkorta, I.; García-Gómez, C.; Páez, J. A.; Goya, P. Theoretical and Experimental Analysis of Properties in Heterocycles Containing the Aminosulphonylamino Moiety. J. Phys. Org. Chem. 1996, 9, 203-211.
9. Campillo, N.; Alkorta, I.; Páez, J. A.; Goya, P. Solvent Effect on the Tautomerism of 4-Aminopyrazino[2,3-c]]1,2,6]Thiadiazine 2,2-Dioxide. J. Chem. Soc., Perkin Trans. 2 1998, 1889-1892.
10. Goya, P.; Páez, J. A.; Alkorta, I.; Carrasco, E.; Grau, M.; Antón, F.; Julia, S.; Martínez-Ripoll, M. N-Substituted Pyrazino[2,3-c]-[1,2,6]thiadiazine 2,2-Dioxides. A New Class of Diuretics. J. Med. Chem. 1992, 35, 3977-3983.
11. García-Muñoz, G.; Madroñero, R.; Ochoa, C.; Stud, M. Synthesis of Purina-Like Ring System Derived From 1,2,6-Thiadiazine 1,1-Dioxide. J. Heterocycl. Chem. 1976, 13, 793-796.
12. Alkorta, I.; Goya, P.; Pãez, J. A.; Pfleiderer, W. Synthesis and Physico-Chemical Properties of 6- and 7-Monosubstituted Pyrazino[2,3-c][1,2,6]thiadiazine 2,2-Dioxides. Pteridines 1990, 2, 3-7.
13. Bertele, V.; Falanga, A.; Tomasiak, M.; Dejana, E.; Carletti, C.; De Gaetano, G. Platelet Thromboxane Synthetase Inhibitors with Low Doses of Aspirin: Possible Resolution of the "Aspirin Dilemma". Science 1983, 220, 517-519.
14. Born, G. V. R. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962, 194, 927-929.
15. Herrero, A.; Ochoa, C. Reaction between o-diamino-1,2,6-thiadiazine 1,1-Dioxides and aldehydes to give fused imidazo and Pyrazino Derivatives. J. Heterocycl. Chem. 1988, 25, 891-893.