I couldn't even imagine demanding a valuable family heirloom from my sister, which she got from her husband's grandmother... Why would I want to give something to my children that I didn't even inherit myself?

This is your painting. I'm pretty sure it is legally, but of course it is emotionally. It belonged to your grandmother and wife, it is important to you.

Your SIL and FIL didn't seem to have a relationship with your grandmother, and since they won't consider you gifting this painting to your potential future children as "keeping it in the family", I'm guessing they weren't even close to you either. The only connection they have with this painting is that your wife loved it.

I get that losing someone isn't a small thing you can glance over in all this. They and you must be devastated and I'm truly sorry for your loss. But your connection to this painting seems so obvious and deep to me, while your in-laws honestly pushy desire to get this painting into their hands asap sounds really icky.

NTA. Keep this painting as a form of piece and remembrance of your wife. Only part with it if it feels right, not because your SIL or someone on the internet told you to.