Posaconazole

Base Information

• Chemical Name: Posaconazole
• CAS No.: 171228-49-2
• Deprecated CAS: 177571-33-4
• Molecular Formula: C37H42F2N8O4
• Molecular Weight: 700.788
• European Community (EC) Number: 682-747-8
• UNII: 6TK1G07BHZ
• DSSTox Substance ID: DTXSID6049066
• Nikkaji Number: J760.534J
• Wikipedia: Posaconazole
• Wikidata: Q906453
• NCI Thesaurus Code: C61500
• RXCUI: 282446
• Pharos Ligand ID: R529WVVT6JA6
• Metabolomics Workbench ID: 63342
• ChEMBL ID: CHEMBL1397
• Mol file: 171228-49-2.mol

Synonyms:4-(p-(4-(p-(((3R,5R)-5-(2,4-difluorophenyl)tetrahydro-5-(1H-1,2,4-triazol-1-ylmethyl)-3-furyl)methoxy)phenyl)-1-piperazinyl)phenyl)-1-((1S,2S)-1-ethyl-2-hydroxypropyl)-delta(sup 2)-1,2,4-triazolin-5-one;Noxafil;posaconazole;posaconazole hydrate;SCH 56592;SCH-56592

Chemical Property of Posaconazole

Chemical Property:

• Appearance/Colour: White solid
• Vapor Pressure: 8.76E-31mmHg at 25°C
• Melting Point: 170-172 °C
• Refractive Index: 1.657
• Boiling Point: 850.7 °C at 760 mmHg
• PKA: 14.72±0.20(Predicted)
• Flash Point: 468.3 °C
• PSA: 115.70000
• Density: 1.36 g/cm³
• LogP: 4.70320
• Storage Temp.: -20°C Freezer
• Solubility.: Chloroform (Slightly), Methanol (Slightly)
• XLogP3: 4.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 11
• Rotatable Bond Count: 12
• Exact Mass: 700.32970817
• Heavy Atom Count: 51
• Complexity: 1170

Purity/Quality:

99%, ^*data from raw suppliers

Posaconazole ^*data from reagent suppliers

Safty Information:

• Pictogram(s): F,T
• Hazard Codes: F,T
• Statements: 11-23/24/25-39/23/24/25
• Safety Statements: 7-16-36/37-45

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antifungal Agents
• Canonical SMILES: CCC(C(C)O)N1C(=O)N(C=N1)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)OCC5CC(OC5)(CN6C=NC=N6)C7=C(C=C(C=C7)F)F
• Isomeric SMILES: CC[C@@H]([C@H](C)O)N1C(=O)N(C=N1)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)OC[C@H]5C[C@](OC5)(CN6C=NC=N6)C7=C(C=C(C=C7)F)F
• Recent ClinicalTrials: Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine (Chemo Combo) in Subjects With Acute Myelogenous Leukemia (AML)
• Recent EU Clinical Trials: Phase I / II, open label, dose escalation part (phase I) followed by non-comparative expansion part (phase II), multi-centre study, evaluating safety, pharmacokinetics and efficacy of S65487, a Bcl2 inhibitor combined with azacitidine in adult patients with previously untreated acute myeloid leukemia not eligible for intensive treatment
• Description: Posaconazole, launched in the UK, is the newest member of the azole class of antifungal agents to reach the market. It is indicated for the treatment and prophylaxis of a range of invasive fungal infections, including aspergillosis,fusariosis, chromoblastomycosis, mycetoma, and coccidiomycosis in patients who are refractory to, or intolerant of, standard therapy with amphotericin B and/or itraconazole. In the US, it is approved for the prophylaxis of invasive Aspergillus and Candida infections in patients 13 years of age who are at high risk of developing these infections due to being severely immunocompromised. Additionally, it is approved for the treatment of oropharyngeal candidiasis. Posaconazole has an expanded spectrum of activity over other members of the azole antifungals. In addition to potent activity against refractory cases of aspergillosis and fluconazole-resistant Candida, it demonstrates activity against Zygomycetes.
• Uses: Posaconazole has been used:in antifungal susceptibility testing of Aspergillus terreusas a lanosterol?14α-demethylase (CYP51)-specific inhibitor to study its effects on membrane permeability in Candida albicans cellsto study its effects on promastigotes Orally active triazole antifungal. Posaconazole is a sterol C14ɑ demethylase inhibitor with an IC50 of 0.25 nM
• Clinical Use: Invasive aspergillosis Fusarium infection Chromoblastomycosis and mycetoma Coccidioidomycosis Oropharyngeal candidosis Prophylaxis of invasive fungal infections in patients at serious risk With the exception of oropharyngeal candidosis and prophylaxis, use is presently restricted to patients with disease that is refractory to other antifungal drugs, or who are intolerant to them.
• Drug interactions: Potentially hazardous interactions with other drugs Analgesics: concentration of fentanyl possibly increased. Anti-arrhythmics: avoid concomitant use with dronedarone. Antibacterials: rifamycins may reduce posaconazole concentration; avoid unless benefit outweighs risk; rifabutin concentration increased. Anticoagulants: avoid with apixiban and rivaroxaban. Antidepressants: avoid concomitant use with reboxetine. Antidiabetics: posaconazole can decrease glucose concentrations, monitor glucose levels in diabetic patients; possibly enhances hypoglycaemic effect of glipizide. Antiepileptics: phenytoin, fosphenytoin, carbamazepine, phenobarbital and primidone may reduce posaconazole concentration - avoid unless benefit outweighs risk. Antimalarials: avoid with artemether/lumefantrine and piperaquine with artenimol. Antipsychotics: increased risk of ventricular arrhythmias with pimozide - avoid; possibly increase quetiapine levels - reduce dose of quetiapine; possibly increases lurasidone concentration - avoid. Antivirals: concentration of atazanavir increased and possibly daclatasvir and simeprevir (reduce dose of daclatasvir, avoid with simeprevir); concentration reduced by efavirenz and possibly fosamprenavir; possibly increases saquinavir levels; increased risk of ventricular arrhythmias with telaprevir; concentration of both drugs increased with dasabuvir and paritaprevir - avoid. Anxiolytics and hypnotics: increases midazolam levels. Ciclosporin: increases posaconazole concentration; posaconazole can increase ciclosporin concentration - dose reduction may be required. Cytotoxics: concentration of bosutinib increased - avoid or reduce dose of bosutinib; possibly increased everolimus concentration - avoid; avoid with lapatinib; reduce dose of panobinostat and ruxolitinib; possibly inhibits metabolism of vinblastine and vincristine, increased risk of neurotoxicity. Ergot alkaloids: may increase ergot alkaloid concentration leading to ergotism - avoid. Guanfacine: possibly increases guanfacine concentration - halve guanfacine dose. Ivacaftor: possibly increased concentration of ivacaftor. Lipid-lowering drugs: avoid with lomitapide; possibly increased risk of myopathy with atorvastatin or simvastatin - avoid.1 Lumacaftor: posaconazole concentration possibly reduced - reduce dose of lumacaftor with ivacaftor. Ranolazine: possibly increased ranolazine concentration - avoid. Sirolimus: may increase concentration of sirolimus - adjust sirolimus dose as required according to levels. Sulphonylureas: posaconazole can decrease glucose concentrations, monitor glucose levels in diabetic patients. Tacrolimus: increases Cmax and AUC of tacrolimus by 121% and 358% respectively - reduce tacrolimus dose to about a third of current dose and adjust as required. Ulcer-healing drugs: cimetidine may reduce posaconazole concentration by 39% - avoid unless benefit outweighs risk; avoid with histamine H2- antagonists and proton pump inhibitors.

Technology Process of Posaconazole

There total 74 articles about Posaconazole 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: 95.8%

C38H42F2N8O5 → posaconazote (171228-49-2)

Guidance literature:

With triethylamine; In methanol; at 60 - 70 ℃; for 1h; Reagent/catalyst; Temperature; Solvent;

Reference yield: 95.0%

4-(4-(4-(4-(((3R,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methoxy)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-(benzyloxy)pentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (170985-86-1) → posaconazote (171228-49-2)

Guidance literature:

With hydrogenchloride; water; at 25 - 63 ℃; Temperature;

Reference yield: 90.0%

C37H44F2N8O5 (1350560-57-4) → posaconazote (171228-49-2)

Guidance literature:

With sodium hydroxide; In water; isopropyl alcohol; for 3h; Solvent; Reagent/catalyst; Time; Temperature; Reflux;

upstream raw materials:

4-(4-(4-(4-(((3R,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methoxy)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-(benzyloxy)pentan-3-yl)-1H-1,2,4-triazol-5(4H)-one

2-((1S,2S)-2-Benzyloxymethoxy-1-ethyl-propyl)-4-[4-(4-{4-[(3R,5R)-5-(2,4-difluoro-phenyl)-5-[1,2,4]triazol-1-ylmethyl-tetrahydro-furan-3-ylmethoxy]-phenyl}-piperazin-1-yl)-phenyl]-2,4-dihydro-[1,2,4]triazol-3-one

(2S,3R)-2-Benzyloxymethoxy-pentan-3-ol

4-Bromo-benzenesulfonic acid (1R,2S)-2-benzyloxymethoxy-1-ethyl-propyl ester

Refernces

• 1、 Jha, Anjali,Krishnam Raju, V. R.. "An Improved Scalable Preparation of the Antifungal Posaconazole". . . Retrieved 2021/11/12.
• 2、 -. "Preparation method of posaconazole". Paragraph 0075-0088. . Retrieved 2020/09/30.