Challenges encountered during development of Mn porphyrin-based, potent redox-active drug and superoxide dismutase mimic, MnTnBuOE-2-PyP5Â +, and its alkoxyalkyl analogues

To improve the bioavailability/toxicity profiles of Mn N-alkylpyridylporphyrin-based redox-active therapeutics, pyridyl quaternization using alkoxyalkyl tosylates was attempted, but in situ tosylate rearrangements yielded mixed N-alkoxyalkylated/N-alkylated pyridylporphyrins. Experimental and computational studies were devised to understand competing N-alkylation during N-alkoxyalkylation, which guided the synthesis of Mn(III) meso-tetrakis-(N-n-butoxyethylpyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP5 + (BMX-001), BMX-001), currently under Clinical Trials.200