Otto Blathy is famous for his long mate problems. There are different records depending on whether you allow an illegal starting position, or promoted pieces, or minor duals in the solution, so your answer might be anywhere between 257 and 292 moves.
This answer on Puzzling.SE shows you a construction in 270 moves:
[Title "Otto Blathy - White to play and mate in 270"]
[FEN "8/Bk3p1p/1P3p2/KP2n2p/1P1p4/1Pp2p2/B1P5/7B w - - 0 1"]
(legal position, with promoted piece, with minor duals in the solution)
Those problems involve regular pawn moves, so the fifty-moves rule doesn't change their validity. On the other hand, all long (500+ moves) tablebase mates (as the first diagram in the answer linked above) show series of more than 50 moves without capture nor pawn moves.
Finally a beautiful problem exploiting the 50-moves rule was composed by Noam Elkies, who comes sometimes on Chess.SE. I will refrain from giving the solution here for people who want to search (but I have already given away the main indication and lazy people can just follow the link).
[Title "Noam Elkies, 1991 - White to play and draw"]
[FEN "8/1p6/1p6/kPp2P1K/2P5/N1Pp4/q2P4/1N6 w - - 0 1"]