Mitapivat was developed by Agios Pharmaceuticals, an American pharmaceutical company, and is approved in the European Union and the United States as an oral treatment for hemolytic anemia and pyruvate kinase deficiency (PKD), a rare inherited disorder associated with chronic hemolytic anemia. In addition to the approved PKD indication, it is currently undergoing clinical studies for the treatment of sickle cell disease and thalassemia.
Mitapivat was approved in the United States in February 2022 and in the European Union in November 2022 for the treatment of hemolytic anemia.
Molecular Formula: C24H26N4O3S
Molecular Weight: 450.55。
CAS：1260075-17-9
Chemical Name：N-(4-(4-(cyclopropylmethyl)piperazine-1-carbonyl)phenyl)isoquinoline-8-sulfonamide
The core compound patent for Mitapivat will expire in 2031. At present, the original research drug has not entered China, and no generic pharmaceutical enterprise has filed an application yet.
Step 1: Boc-piperazine undergoes reductive amination with excess cyclopropanecarboxaldehyde to obtain the desired tertiary amine, and Boc is removed with acid to obtain cyclopropylmethylpiperazine.
Step 2: The sulfonyl chloride reacts with aniline to obtain sulfonamide with a yield of 99%
Step 3: The ester group is hydrolyzed to a carboxylic acid under alkaline conditions, with a yield of 91%
Step 4: Activate the carboxylic acid with CDI, then conduct a condensation reaction with cyclopropylmethylpiperazine, add water to the reaction to induce crystallization, and obtain Mitapivat with a 90% isolated yield.
