Upacicalcet

Upacicalcet is an intravenous calcimimetic agent. Upacicalcet suppresses excessive parathyroid hormone (PTH) secretion, thereby lowering blood PTH levels, by acting directly on parathyroid cell membrane calcium-sensing receptors. Upacicalcet can be used for researching the disease of secondary hyperparathyroidism (SHPT)[1].

Upacicalcet works by directly acting on the calcium-sensing receptors on the parathyroid cell membrane, inhibiting excessive parathyroid hormone (PTH) secretion, thereby reducing PTH levels in the blood. PTH is a hormone that regulates calcium concentration in the blood to maintain calcium balance in body tissues.

Synthesis of Upacicalcet as a hydrated sodium salt: Aniline 24.1 was reacted with phenyl chloroformate before treatment with amine 24.2 and base to give urea 24.3 in excellent conversion. Removal of Boc and tert-butyl esters in methanesulfonic acid afforded the hydrated methanesulfonate 24.4. Treatment of this sulfonic acid with sodium hydroxide followed by careful pH adjustment in isopropanol afforded the hydrated sodium salt of Upacicalcet (24).

[1] Hoy SM. Upacicalcet: First Approval. Drugs. 2021;81(13):1593-1596. DOI:10.1007/s40265-021-01578-y