When we've done road trips with the kids, at the same ages, we stopped every 2-3 hours for a break. It's frustrating and takes up all the time but it was truly the only way we could keep the peace and enjoy any part of the trip.
Unless you're going to put both in diapers and line the seats with plastic you have to stop frequently. Kids don't feel pain like adults do. We recognize we're stiff and then we stretch the muscles out. Kids just feel cranky and they don't even know they're starting to feel pain. Those car seats aren't as cushy as we think. They can't move like we do either. They're strapped in totally. Even if they fall asleep they can't stretch anything.
We'd get up, eat full breakfast at the hotel, shower and pack, load up, get on the road sort of early but not crack of dawn.
Then we'd stop around 9:30am-10am for morning snacks and play time. In hot weather we always stopped at McDonald's to have parfaits or something. The kids could run around and work out some kinks.
Then on the road until lunch. Good solid lunch will do wonders for them once they get back in the car. They should go to sleep with that full tummy and not wake up for at least a couple of hours. You should drive as long as possible here.
Once they wake up it's potty time. Then snacks and movement for at least 10-15 minutes. The back on the road. They're going to start feeling the effects of the seats by now and you may have to hold them down to fasten their straps. Ours never wanted to get back in the seat at this point.
It's up to you at this point. You're tired and ready to be there already, thinking about when they're asleep and you can lay down, how much you would love to have a massage...lol.
If you are stopping for the night it wouldn't hurt to pick a hotel that has a pool or some area where the kids can be kids and play. The cool water will help stop any pain from sitting by reducing any inflammation.
Part of the trip should be for play. It's not just about getting from point A to point B for kids. That's sheer torture for their little minds.
When we traveled we always picked several places that we could stop and do the sightseeing stuff or some other experience. Like if we have friends traveling through OKC we'd tell them to stop in the Bricktown area. There's a rock climbing place that has a super tall wall. They have toddlers climb too. It's totally fun!
The kids will remember this trip, even though they're young they will remember things about it. I went to Cherry Point when my brother was stationed there. I was pretty young. I remember passing a river that looked like it was flowing uphill. I remember stopping to look at quilts along the highway. I remember waking up at a motel and there was a water feature where the spigot ran water into the pool below. The water pipe went up inside the flow of water coming down but to a kid it was magic!
I remember my mom washing my dad's face with a wet rag she was holding in front of the air conditioner so he could stay awake. We wanted to get to my brother's house that night. It was very very late. I don't think I had started school yet. I remembered odd things. Pictures helped too. I have those pictures in my scrapbooks and my grand kids love looking at them too. Seeing me on vacation with my mom and dad is funny to them.
SO plan out your stops before you leave. Plan the trip you want. Do you want to enjoy the trip to and from the location as well as the location part?
If not then consider taking a 2nd driver and drive through the night. Then stop for breakfast, switch drivers, do the frequent stops during the day, let the other driver sleep as much as possible, then drive as far as possible the 2nd night but plan on stopping at some point so both drivers will be safe the 3rd day.