In the 3rd century BCE, the region was occupied by the contingents of Alexander the Great's Macedonian army, but many insurrections had also taken place in this era as the Macedonian occupiers couldn't build up a total control on the region.
After the collapse of Alexander's Empire (as Alexander died in 323 BCE), the region was taken over by the Pontus Kingdom founded on the Black Sea coast who later had to retreat in the face of emerging Roman power in the whole Anatolia.