1H-Indazoles are incredibly rare in nature but the diverse pharmacological properties imparted to molecules containing this nucleus has catapulted them firmly into the drug designer’s toolkit^[1]... Indeed, molecules presenting the 1H-indazole motif are widely incorporated in multiple drugs such as anti-HIV, anti-inflammatory and anti-cancer drugs^[2], and many examples have been proved that 1H-Indazoles have featured in the development of drugs spanning a range of pathophysiologies, such as bendazac (anti-inflammation) and axitinib (anti-cancer) as well as gamendazole (a drug candidate for male contraception) ^{[1, 3-5]}.

The pyrazine unit is an important structural motif that widely existed in many bioactive and nature compounds.^[1] Pyrazine derivatives have attracted wide pharmaceutical interests because of their potential uses...
in the treatment of psychiatric disorders, neurological diseases (e.g., stress, anxiety and depression), and cardiovascular disorders.^[2] They are reported to modulate the activity of CRF1 (corticotropin-releasing factor 1) receptors. Besides, they are also versatile building blocks in the synthesis of VCAM-1 (vascular cell adhesion molecule-1) inhibitors, pyrazine alkaloids (antineoplasmic activity), and imidazopyrazin coelenterazine (bioluminescent). ^[2] In recent years, pyrazine scaffold has been found in more and more drug molecules.^[3-7]