Cinacalcet hydrochloride
[CAS# 364782-34-3]

Identification

• Classification: Biochemical >> Inhibitor >> G protein coupled receptor(GPCR & G Protein) >> CaSR activator
• Name: Cinacalcet hydrochloride
• Synonyms: N-((1R)-1-(1-Naphthyl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amine hydrochloride
• Molecular Formula: C₂₂H₂₂F₃N.HCl
• Molecular Weight: 393.88
• CAS Registry Number: 364782-34-3
• EC Number: 620-490-5
• SMILES: C[C@H](C1=CC=CC2=CC=CC=C21)NCCCC3=CC(=CC=C3)C(F)(F)F.Cl

Properties

• Solubility: 2 mg/mL (DMSO)

Safety Data

• Hazard Symbols: GHS05;GHS07;GHS08;GHS09 Danger
• Risk Statements: H302-H312-H315-H317-H318-H319-H373-H400-H410-H412-H413
• Safety Statements: P260-P261-P264-P264+P265-P270-P272-P273-P280-P301+P317-P302+P352-P305+P351+P338-P305+P354+P338-P317-P319-P321-P330-P332+P317-P333+P317-P337+P317-P362+P364-P391-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Serious eye damage	Eye Dam.	1	H318
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Skin sensitization	Skin Sens.	1	H317
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H312
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412

Discovery and Applications

Cinacalcet hydrochloride is a calcium-sensing receptor (CaSR) agonist primarily used in the treatment of hyperparathyroidism and related conditions. It is a small molecule compound that selectively enhances the sensitivity of the parathyroid gland to extracellular calcium levels, thereby inhibiting parathyroid hormone (PTH) secretion. This compound has gained significant attention for its therapeutic benefits in managing disorders related to calcium imbalance, including secondary hyperparathyroidism in chronic kidney disease (CKD) patients and primary hyperparathyroidism.

The discovery of cinacalcet hydrochloride can be traced back to research aimed at regulating calcium homeostasis through the modulation of CaSR activity. The calcium-sensing receptor is involved in the feedback mechanism that controls calcium levels in the blood by regulating the release of PTH from the parathyroid glands. The development of cinacalcet hydrochloride stemmed from efforts to create drugs that could mimic the effect of elevated calcium concentrations, thereby reducing excessive PTH secretion. In 2004, cinacalcet hydrochloride was approved by the U.S. Food and Drug Administration (FDA) for the treatment of secondary hyperparathyroidism in patients undergoing dialysis, and later for the treatment of primary hyperparathyroidism.

The synthesis of cinacalcet hydrochloride involves the construction of a complex heterocyclic structure, with key steps including the formation of a piperazine ring and the introduction of a benzyl group. The synthesis pathway typically requires the use of various reagents, such as chloroformates, and includes multiple purification steps to ensure the final product's purity and stability. Given its pharmacological importance, the synthetic process is designed to yield high-quality cinacalcet hydrochloride with minimal by-products.

In terms of application, cinacalcet hydrochloride has shown significant clinical efficacy in reducing elevated PTH levels, which are often associated with renal disease and certain bone disorders. In CKD, particularly in patients on dialysis, secondary hyperparathyroidism leads to disturbances in bone mineralization, vascular calcification, and other complications. By reducing PTH secretion, cinacalcet helps mitigate these risks and improve the quality of life for patients. The drug is also used to manage primary hyperparathyroidism, a condition characterized by overproduction of PTH, often leading to bone loss, kidney stones, and fatigue.

In addition to its primary clinical applications, cinacalcet hydrochloride has also been explored in various research settings for its potential to treat other disorders related to calcium and bone metabolism, including osteoporosis and certain malignancies. Ongoing studies continue to investigate its broader therapeutic uses, including its impact on cardiovascular health and its potential as an adjunct to other treatments for bone diseases.

In conclusion, cinacalcet hydrochloride is an important pharmacological agent with significant applications in treating calcium-related disorders, particularly in patients with hyperparathyroidism. Its ability to regulate PTH secretion via CaSR modulation has proven beneficial in clinical practice, and ongoing research may reveal even more uses for this versatile compound.

References

2013. Cinacalcet. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-03-0121