Adenosine is a ubiquitous biochemical messenger. Adenosine binds to and activates seven-transmembrane spanning G-protein coupled receptors, eliciting a variety of physiological responses. Adenosine receptors are divided into four known subtypes (i.e., A1, A2a, A2b, and A3). These receptor subtypes mediate different, and sometimes opposing, effects. Activation of the adenosine A1 receptor, for example, elicits an increase in renal vascular resistance, while activation of the adenosine A2a receptor elicits a decrease in renal vascular resistance. Accordingly, adenosine antagonists are useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable.
Some 2-aminopyridine compounds to exhibit adenosine receptor antagonism are known (WO 02/14282, WO 01/25210, etc.), and some 2-aminopyrimidine compounds are also known (WO 03/035639, U.S. 2001/0027196, etc.).
However, it is generally difficult to produce a pyrazine which is substituted by four different substituents, and for example the synthesis of a pyrazine compound of the formula A:
                wherein Ar and Ar′ are independently same or different aryl; and                    R, R′ and M are independently hydrogen or suitable substituent;is reported (e.g. (1) J.Org. Chem., 40, 2341 (1975), (2) J.Heterocyclic Chem., 15, 665 (1978), (3) J.Chem.Soc.Perkin Trans.1, 1994, 885, (4) Synthesis, 1994, 931, (5) WO-02/088084, etc.), however practically, the Ar and Ar′ thereof are same, and the selective synthesis of a pyrazine compound A wherein Ar and Ar′ are different is not shown as far as we know, and 6-aryl-5-(6-oxo-1,6-dihydro-pyridazin-3-yl)-pyrazine compounds and derivatives thereof are novel, so there has been no knowledge about these compounds, so far. In addition, any pyrazine derivatives having both of adenosine A1 and A2a inhibitory activities are not known.                        