Ciclesonide

Base Information

• Chemical Name: Ciclesonide
• CAS No.: 126544-47-6
• Deprecated CAS: 141845-82-1
• Molecular Formula: C32H44O7
• Molecular Weight: 540.697
• Hs Code.: 2937229000
• European Community (EC) Number: 685-344-5
• UNII: S59502J185
• DSSTox Substance ID: DTXSID9046659
• Nikkaji Number: J561.842H
• Wikipedia: Ciclesonide
• Wikidata: Q5119448
• NCI Thesaurus Code: C65326
• RXCUI: 274964
• Pharos Ligand ID: U92GRBX86HV5
• Metabolomics Workbench ID: 146070
• ChEMBL ID: CHEMBL2040682
• Mol file: 126544-47-6.mol

Synonyms:(R)-11beta,16alpha,17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with cyclohexanecarboxaldehyde, 21-isobutyrate;Alvesco;ciclesonide;Omnaris

Chemical Property of Ciclesonide

Chemical Property:

• Vapor Pressure: 1.61E-20mmHg at 25°C
• Melting Point: 202-209?C
• Refractive Index: 1.575
• Boiling Point: 665 °C at 760 mmHg
• PKA: 14.25±0.70(Predicted)
• Flash Point: 210 °C
• PSA: 99.13000
• Density: 1.23 g/cm³
• LogP: 4.70390
• Storage Temp.: Refrigerator
• Solubility.: Chlorofrom (Slightly), Methanol (Slightly)
• XLogP3: 5.3
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 6
• Exact Mass: 540.30870374
• Heavy Atom Count: 39
• Complexity: 1100

Purity/Quality:

99%min ^*data from raw suppliers

Ciclesonide ≥98%(HPLC) ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)C(=O)OCC(=O)C12C(CC3C1(CC(C4C3CCC5=CC(=O)C=CC45C)O)C)OC(O2)C6CCCCC6
• Isomeric SMILES: CC(C)C(=O)OCC(=O)[C@@]12[C@@H](C[C@@H]3[C@@]1(C[C@@H]([C@H]4[C@H]3CCC5=CC(=O)C=C[C@]45C)O)C)O[C@H](O2)C6CCCCC6
• Recent ClinicalTrials: Comparison Between Systemic Exposure to Ciclesonide Nasal Spray, Ciclesonide HFA Nasal Aerosol and Orally Inhaled Ciclesonide (BY9010/M1-422)
• Recent EU Clinical Trials: The CIMMCov-study: A Single-center, Double-blinded, Randomized, 28-days, Parallel-group, study to evaluate the effect of Ciclesonide 320 mcg inhalation twice daily versus placebo on healthcare utilization, disease progression and symptoms in the treatment of mild-to-moderate COVID-19.
• Recent NIPH Clinical Trials: Combination therapy of favipiravir, camostat mesilate and inhaled ciclesonide for COVID-19 pneumonia
• Description: Ciclesonide, a new inhaled corticosteroid (ICS), is indicated for the prophylactic treatment of persistent asthma. ICS treatment is a widely accepted standard of care for maintenance therapy of chronic asthma, and the currently available agents include fluticasone propionate, budesonide, triamcinolone acetonide, flunisolide, and beclomethasone dipropionate. These agents exert their potent anti-inflammatory effects via modulation of the glucocorticoid receptor (GR). Although ICS drugs are generally safe and well tolerated compared with oral corticosteroids, many have measurable systemic exposures, and concerns over potential side effects resulting from it severely limit the dose at which they can be administered for long-term therapy. Systemic adverse effects associated with corticosteroids include HPA axis suppression, osteoporosis, abnormal glucose metabolism, cataracts, and glaucoma, some of which could potentially occur with the long-term use of high dose ICS. The key differentiators for ciclesonide relative to other ICS drugs are its longer duration of action and lower systemic exposure. Ciclesonide is an isobutyryl ester prodrug. It is cleaved by the endogenous esterases in the lung to des-isobutyryl ciclesonide (des- CIC), which is a potent GR agonist. The binding affinity of des-CIC for human GR (Ki=0.31 nM) is similar to other ICS such as budesonide (Ki=0.44nM) and fluticasone propionate (Ki=0.24nM), while ciclesonide itself has about 100-fold lower affinity (Ki=37nM). In lung tissue, des-CIC undergoes reversible lipid conjugation to form oleate and palmitate ester conjugates, which act as a slow-release pool for the drug and increase the pulmonary residence time. This, in turn, contributes to the enhanced local effects and the long duration of action. Inhaled ciclesonide was generally well tolerated in these clinical studies. Ciclesonide did not suppress biochemical markers of adrenal function in 52-week studies; however, the long-term (＞52 weeks) systemic effects remain unknown. Ciclesonide is chemically produced via a semi-synthesis starting from 16-α-hydroxyprednisolone by first converting to a triisobutyryl ester intermediate with isobutyric anhydride, and subsequent reaction of the triester with cyclohexane carboxaldehyde and hydrochloric acid in dioxane. The latter step produces the cyclic ketal as a mixture of diastereomers, which is subjected to HPLC and fractional crystallization to produce ciclesonide.
• Uses: A glucocorticoid microemulsion nasal preparation allergy inhibitor rhinitis. A glucocorticoid microemulsion nasal preparation allergy inhibitor rhinitis

Technology Process of Ciclesonide

There total 21 articles about Ciclesonide which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 88.0%

11β,16α,17α-trihydroxypregna-21-(2-methyl-1-oxopropoxy)-1,4-diene-3,20-dione (886861-17-2) + cyclohexanecarbaldehyde (2043-61-0) → ciclesonide (126544-47-6,141845-82-1)

Guidance literature:

With boron trifluoride; In tetrahydrofuran; dichloromethane; at 5 - 20 ℃; for 4h;

Reference yield:

desisobutyryl ciclesonide (161115-59-9) + 2-Methylpropionic anhydride (97-72-3) → ciclesonide (126544-47-6,141845-82-1)

Guidance literature:

With pyridine; at 0 - 20 ℃;

Reference yield:

potassium isobutyrate (19455-20-0) + 21-bromo-16α,17-[(R)-cyclohexylmethylenedioxy]-11β-hydroxypregna-1,4-dien-3,20-dione (1451396-66-9) → ciclesonide (126544-47-6,141845-82-1)

Guidance literature:

In 1-methyl-pyrrolidin-2-one; at 50 ℃; for 5h; Time;

upstream raw materials:

11β,16α,17α-trihydroxypregna-21-(2-methyl-1-oxopropoxy)-1,4-diene-3,20-dione

cyclohexanecarbaldehyde

desonide 21-isobutyrate

desisobutyryl ciclesonide

Downstream raw materials:

C₄₂H₅₇NO₁₄

C₄₂H₅₇NO₁₄

C₄₀H₅₄O₁₃

C₃₄H₄₈O₁₀

Refernces

• 1、 -. "Ciclesonide preparation method". Paragraph 0016; 0017; 0021-0023; 0026-0028; 0031; 0032. . Retrieved 2019/02/13.
• 2、 -. "NOVEL PROCESS FOR PREPARATION OF GLUCOCORTICOID STEROIDS". Page/Page column 18. . Retrieved 2016/08/23.