[(1R)-1-(naphthalen-1-yl)ethyl]({3-[3-(trifluoromethyl)phenyl]propyl})amine

• ChemBase ID: 885
• Molecular Formular: C22H22F3N
• Molecular Mass: 357.4119896
• Monoisotopic Mass: 357.17043437
• SMILES: FC(F)(F)c1cc(CCCN[C@@H](c2c3c(ccc2)cccc3)C)ccc1
• Canonical SMILES: C[C@H](c1cccc2c1cccc2)NCCCc1cccc(c1)C(F)(F)F
• InChI: InChI=1S/C22H22F3N/c1-16(20-13-5-10-18-9-2-3-12-21(18)20)26-14-6-8-17-7-4-11-19(15-17)22(23,24)25/h2-5,7,9-13,15-16,26H,6,8,14H2,1H3/t16-/m1/s1
• InChIKey: VDHAWDNDOKGFTD-MRXNPFEDSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: [(1R)-1-(naphthalen-1-yl)ethyl]({3-[3-(trifluoromethyl)phenyl]propyl})amine
• IUPAC Traditional name: cinacalcet
• Brand Name: Sensipar
• Synonyms: Cinacalcet

Database IDs

• CAS Number: 226256-56-0
• PubChem SID: 160964348; 46506315
• PubChem CID: 156419

CALCULATED PROPERTIES

JChem

• H Acceptors: 1
• H Donor: 1
• LogD (pH = 5.5): 3.042948
• LogD (pH = 7.4): 3.5335772
• Log P: 6.273198
• Molar Refractivity: 100.1173 cm^3
• Polarizability: 38.956448 Å^3
• Polar Surface Area: 12.03 Å^2
• Rotatable Bonds: 7
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 5.57
• LOG S: -6.81
• Solubility (Water): 5.59e-05 g/l

PROPERTIES

Physical Property

• Solubility: Slightly soluble (in HCl salt form)
• Hydrophobicity(logP): 6.5

DETAILS

DrugBank - DB01012

• Drug Groups: approved
• Description: Cinacalcet (INN) is a drug that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues) by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues. It is sold by Amgen under the trade name Sensipar? in North America and Australia and as Mimpara? in Europe. Cinacalcet is used to treat hyperparathyroidism (elevated parathyroid hormone levels), a consequence of parathyroid tumors and chronic renal failure.
• Indication: For the treatment of secondary hyperparathyroidism in patients with Chronic Kidney Disease who are on hemodialysis or peritoneal dialysis. Also for the treatment of hypercalcemia in patients with parathyroid carcinoma.
• Pharmacology: Cinacalcet is a drug that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues). Secondary hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) is a progressive disease, associated with increases in parathyroid hormone (PTH) levels and derangements in calcium and phosphorus metabolism. Increased PTH stimulates osteoclastic activity resulting in cortical bone resorption and marrow fibrosis. The goals of treatment of secondary hyperparathyroidism are to lower levels of PTH, calcium, and phosphorus in the blood, in order to prevent progressive bone disease and the systemic consequences of disordered mineral metabolism. In CKD patients on dialysis with uncontrolled secondary HPT, reductions in PTH are associated with a favorable impact on bone-specific alkaline phosphatase (BALP), bone turnover and bone fibrosis. Cinacalcet reduces calcium levels by increasing the sensitivity of the calcium sensing receptor to extracellular calcium.
• Toxicity: Doses titrated up to 300 mg once daily have been safely administered to patients on dialysis. Overdosage of cinacalcet may lead to hypocalcemia.
• Affected Organisms: Humans and other mammals
• Biotransformation: Metabolism is hepatic by multiple enzymes, primarily CYP3A4, CYP2D6, and CYP1A2. After administration of a 75 mg radiolabeled dose to healthy volunteers, cinacalcet was rapidly and extensively metabolized via: 1) oxidative N-dealkylation to hydrocinnamic acid and hydroxy-hydrocinnamic acid, which are further metabolized via ß-oxidation and glycine conjugation; the oxidative N-dealkylation process also generates metabolites that contain the naphthalene ring; and 2) oxidation of the naphthalene ring on the parent drug to form dihydrodiols, which are further conjugated with glucuronic acid.
• Absorption: Rapidly absorbed following oral administration.
• Half Life: Terminal half-life is 30 to 40 hours. The mean half-life of cinacalcet is prolonged by 33% and 70% in patients with moderate and severe hepatic impairment, respectively.
• Protein Binding: Approximately 93 to 97% bound to plasma proteins.
• Elimination: Cinacalcet is metabolized by multiple enzymes, primarily CYP3A4, CYP2D6 and CYP1A2. Renal excretion of metabolites was the primary route of elimination of radioactivity.
• Distribution: * 1000 L
• References: Torres PU: Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease. J Ren Nutr. 2006 Jul;16(3):253-8. [Pubmed] ; Padhi D, Harris R: Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11. doi: 10.2165/00003088-200948050-00002. [Pubmed] ; Dong BJ: Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. 2005 Nov;27(11):1725-51. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Torres PU: Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease. J Ren Nutr. 2006 Jul;16(3):253-8. Pubmed
• Padhi D, Harris R: Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11. doi: 10.2165/00003088-200948050-00002. Pubmed
• Dong BJ: Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. 2005 Nov;27(11):1725-51. Pubmed