2-[(1S,2S,4R,8S,9S,11S,12S,13R)-6-cyclohexyl-11-hydroxy-9,13-dimethyl-16-oxo-5,7-dioxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosa-14,17-dien-8-yl]-2-oxoethyl 2-methylpropanoate

• ChemBase ID: 1219
• Molecular Formular: C32H44O7
• Molecular Mass: 540.68756
• Monoisotopic Mass: 540.30870375
• SMILES: O1[C@]2([C@@]3([C@H]([C@H]4[C@H]([C@@H](O)C3)[C@@]3(C(=CC(=O)C=C3)CC4)C)C[C@H]2OC1C1CCCCC1)C)C(=O)COC(=O)C(C)C
• Canonical SMILES: O=C(C(C)C)OCC(=O)[C@@]12OC(O[C@@H]1C[C@@H]1[C@]2(C)C[C@H](O)[C@H]2[C@H]1CCC1=CC(=O)C=C[C@]21C)C1CCCCC1
• InChI: InChI=1S/C32H44O7/c1-18(2)28(36)37-17-25(35)32-26(38-29(39-32)19-8-6-5-7-9-19)15-23-22-11-10-20-14-21(33)12-13-30(20,3)27(22)24(34)16-31(23,32)4/h12-14,18-19,22-24,26-27,29,34H,5-11,15-17H2,1-4H3/t22-,23-,24-,26+,27+,29?,30-,31-,32+/m0/s1
• InChIKey: LUKZNWIVRBCLON-FOMURGDPSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-[(1S,2S,4R,8S,9S,11S,12S,13R)-6-cyclohexyl-11-hydroxy-9,13-dimethyl-16-oxo-5,7-dioxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosa-14,17-dien-8-yl]-2-oxoethyl 2-methylpropanoate
• IUPAC Traditional name: ciclesonide
• Brand Name: Alvesco
• Synonyms: ciclesonide; Ciclesonide

Database IDs

• CAS Number: 141845-82-1
• PubChem SID: 46508553; 160964679
• PubChem CID: 444033

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.7785225
• H Acceptors: 6
• H Donor: 1
• LogD (pH = 5.5): 5.3232727
• LogD (pH = 7.4): 5.3232727
• Log P: 5.3232727
• Molar Refractivity: 146.2789 cm^3
• Polarizability: 57.75212 Å^3
• Polar Surface Area: 99.13 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 4.08
• LOG S: -5.54
• Solubility (Water): 1.57e-03 g/l

DETAILS

DrugBank - DB01410

• Drug Groups: approved; investigational
• Description: Ciclesonide is a glucocorticoid used to treat obstructive airway diseases. It is marketed under the brand name Alvesco.
• Indication: For the treatment of nasal symptoms associated with seasonal and perennial allergic rhinitis in adults and adolescents 12 years of age and older.
• Pharmacology: Ciclesonide is a pro-drug that is enzymatically hydrolyzed to a pharmacologically active metabolite, C21-desisobutyryl-ciclesonide (des-ciclesonide or RM1) following intranasal application. Des-ciclesonide has anti-inflammatory activity with affinity for the glucocorticoid receptor that is 120 times higher than the parent compound. The precise mechanism through which ciclesonide affects allergic rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic inflammation.
• Affected Organisms: Humans and other mammals
• Biotransformation: Des-ciclesonide undergoes metabolism in the liver to additional metabolites mainly by the cytochrome P450 (CYP) 3A4 isozyme and to a lesser extent by CYP 2D6.
• Absorption: Ciclesonide and des-ciclesonide have negligible oral bioavailability (both less than 1%) due to low gastrointestinal absorption and high first-pass metabolism. The intranasal administration of ciclesonide at recommended doses results in negligible serum concentrations of ciclesonide.
• Protein Binding: The percentage of ciclesonide and des-ciclesonide bound to human plasma proteins averaged ≥ 99% each, with ≤ 1% of unbound drug detected in the systemic circulation.
• Clearance: * 152 L/hr [Following IV administration of 800 mcg of ciclesonide]
• References: Mutch E, Nave R, McCracken N, Zech K, Williams FM: The role of esterases in the metabolism of ciclesonide to desisobutyryl-ciclesonide in human tissue. Biochem Pharmacol. 2007 May 15;73(10):1657-64. Epub 2007 Jan 28. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Mutch E, Nave R, McCracken N, Zech K, Williams FM: The role of esterases in the metabolism of ciclesonide to desisobutyryl-ciclesonide in human tissue. Biochem Pharmacol. 2007 May 15;73(10):1657-64. Epub 2007 Jan 28. Pubmed