I would be inclined to speak to your son and be honest. Obviously it is up to them how they spend their money. But, in answer to your question, I can see why you would be annoyed, and under those circumstances I would tell your son if they can afford to support his wife's relatives that's their lookout, but you will refrain from giving them your cash to do this with. You could reassure your son that if he and his wife ever really need some money they are welcome to ask you and, if you have it, you might help them out. Make it clear you are not a bank to support the wider extended family. If that other couple have chosen to live their life spending beyond their means, acquiring debts, and their relationship has also gone down the swanee, why the hell should you be expected to fund their next car, holiday, home improvements designer clothes, or whatever the hell it is they want extra money for. Let your son and his wife manage their own finances. Let your son and his wife support her relatives if that is what they choose to do. But don't let any of them use your cash to do this. Tell your son if he and his wife can manage OK with their own money there may be more of yours to inherit at a later date!
Personally I would have a frank conversation to your son, explain your reasons - I'm sure he will understand. They may have appreciated the financial gifts your have given them but if they don't NEED it, don't give it...they can't NEED it that much if they are considering giving it away to her brother & his partner...or, in your own words, "subsidise them". The couple (soon to be 2 single people from the sound if it) need to learn to curb their spending or better prioritise what they spend it on - they will never get to this point if continuing to build debts and ponce off relatives they guilt-trip into funding their next extravagance.
And, lastly, WTF are your sons in-laws doing trying to influence how their daughter and her husband spend their money. Why the hell would they think it is OK to ask them to "subsidise" other family members? If the in-laws want to support the irresponsible brother let them do it themselves - what a damned cheek. It often surprises me on these threads just how much some people feel entitled to interfere in the lives of friends and/or family and/or work colleagues. Keep your "hard earned money" and spend it on yourselves, save it, invest it etc - it is yours to do with as you wish and you obviously don't fancy watching someone else just squander it, so don't. Good luck. And if the in-laws stick their beaks in again, tell them to use their own bloody money.