These kids are mobile and looking for stuff to get into. A long drive with them can sour the entire outing if you don't keep them fed and occupied. Assemble a bag with items that they have never seen before and give it to them when they get in the car, not before. Have a second bag for the return trip. Coloring books, crayons and little silly things aren't too expensive and they will make things much easier on your nerves.
Plan stops and have snacks already measured into individual containers.
Getting out of the car at regular intervals can save your sanity, but it may also impact the distance that you can go. On one trip to Florida, I think we stopped at every single rest area between Atlanta and Tampa for some reason or another. Didn't think we would ever get there. Don't feed the kids snacks with too much sugar or salt, either. This age group loves to sing.