(1R,3R)-5-{2-[(1R,3aS,4E,7aR)-1-[(2R,3E,5S)-6-hydroxy-5,6-dimethylhept-3-en-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}cyclohexane-1,3-diol

• ChemBase ID: 786
• Molecular Formular: C27H44O3
• Molecular Mass: 416.63646
• Monoisotopic Mass: 416.32904527
• SMILES: OC([C@H](/C=C/[C@H]([C@@H]1[C@@]2([C@@H](CC1)/C(=C/C=C/1\C[C@@H](O)C[C@H](O)C1)/CCC2)C)C)C)(C)C
• Canonical SMILES: O[C@H]1C[C@H](O)C/C(=C\C=C\2/CCC[C@]3([C@H]2CC[C@@H]3[C@@H](/C=C/[C@@H](C(O)(C)C)C)C)C)/C1
• InChI: InChI=1S/C27H44O3/c1-18(8-9-19(2)26(3,4)30)24-12-13-25-21(7-6-14-27(24,25)5)11-10-20-15-22(28)17-23(29)16-20/h8-11,18-19,22-25,28-30H,6-7,12-17H2,1-5H3/b9-8+,21-11+/t18-,19+,22-,23-,24-,25+,27-/m1/s1
• InChIKey: BPKAHTKRCLCHEA-UBFJEZKGSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1R,3R)-5-{2-[(1R,3aS,4E,7aR)-1-[(2R,3E,5S)-6-hydroxy-5,6-dimethylhept-3-en-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}cyclohexane-1,3-diol
• IUPAC Traditional name: paricalcitol
• Brand Name: Zemplar
• Synonyms: (1R,3R,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-Octahydro-1-[(1R,2E,4S)-5-hydroxy-1,4,5-trimethyl-2-hexen-1-yl]-7a-methyl-4H-inden-4-ylidene]ethylidene]-1,3-cyclohexanediol; (1α,3β,7E,22E)-19-Nor-9,10-secoergosta-5,7,22-triene-1,3,25-triol; 19-Nor-1,25-dihydroxyvitamin D2; 1α,25-Dihydroxy-19-nor-vitamin D2; Zemplar; paricalcitol; Paricalcitol

Database IDs

• CAS Number: 131918-61-1
• PubChem SID: 46505780; 160964249
• PubChem CID: 5281104

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.811643
• H Acceptors: 3
• H Donor: 3
• LogD (pH = 5.5): 4.2585115
• LogD (pH = 7.4): 4.2585115
• Log P: 4.2585115
• Molar Refractivity: 127.9486 cm^3
• Polarizability: 49.421616 Å^3
• Polar Surface Area: 60.69 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 5.27
• LOG S: -4.79
• Solubility (Water): 6.80e-03 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; Methanol
• Apperance: White Solid
• Melting Point: 172-176°C
• Hydrophobicity(logP): 4.5

DETAILS

DrugBank - DB00910

• Drug Groups: approved; investigational
• Description: Paricalcitol is a synthetic vitamin D analog. Paricalcitol has been used to reduce parathyroid hormone levels. Paricalcitol is indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure.
• Indication: For treatment of secondary hyperparathyroidism associated with chronic kidney disease (CKD) Stage 3 and 4
• Pharmacology: Secondary hyperparathyroidism is characterized by an elevation in parathyroid hormone (PTH) associated with inadequate levels of active vitamin D hormone. The source of vitamin D in the body is from synthesis in the skin and from dietary intake. Vitamin D requires two sequential hydroxylations in the liver and the kidney to bind to and to activate the vitamin D receptor (VDR). The endogenous VDR activator, calcitriol [1,25(OH)2 D3], is a hormone that binds to VDRs that are present in the parathyroid gland, intestine, kidney, and bone to maintain parathyroid function and calcium and phosphorus homeostasis, and to VDRs found in many other tissues, including prostate, endothelium and immune cells. VDR activation is essential for the proper formation and maintenance of normal bone. In the diseased kidney, the activation of vitamin D is diminished, resulting in a rise of PTH, subsequently leading to secondary hyperparathyroidism and disturbances in the calcium and phosphorus homeostasis.1 Decreased levels of 1,25(OH)2 D3 have been observed in early stages of chronic kidney disease. The decreased levels of 1,25(OH)2 D3 and resultant elevated PTH levels, both of which often precede abnormalities in serum calcium and phosphorus, affect bone turnover rate and may result in renal osteodystrophy. An in vitro study indicates that paricalcitol is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A at concentrations up to 50 nM (21 ng/mL).
• Affected Organisms: Humans and other mammals
• Biotransformation: Metabolized by multiple hepatic and non-hepatic enzymes, including mitochondrial CYP24, as well as CYP3A4 and UGT1A4
• Absorption: Well absorbed
• Half Life: 4 to 6 hours
• Protein Binding: 99.8% (bound to plasma proteins)
• Elimination: Paricalcitol is excreted primarily by hepatobiliary excretion.
• Distribution: * 30.8 ± 7.5 L [CKD Stage 5-HD]; * 34.9 ± 9.5 L [CKD Stage 5-PD]; * 23.8 L [healthy subjects]
• Clearance: * 1.49 +/- 0.60 L/h [chronic kidney disease Stage 5 with hemodialysis]; * 1.54 +/- 0.95 L/h [chronic kidney disease Stage 5with peritoneal dialysis]
• External Links: RxList; Drugs.com

Toronto Research Chemicals - P195300

Synthetic analog of vitamin D. Antihyperparathyroid.

REFERENCES

• Sidek, H., et al.: Biochim. Biophys. Acta, 801, 26 (1984)
• Ciftci, M., et al.: J. Pharmacol., 54, 275 (1984)