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171228-49-2 molecular structure
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4-{4-[4-(4-{[(5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-1-[(2S,3S)-2-hydroxypentan-3-yl]-4,5-dihydro-1H-1,2,4-triazol-5-one

ChemBase ID: 1131
Molecular Formular: C37H42F2N8O4
Molecular Mass: 700.7773864
Monoisotopic Mass: 700.3297083
SMILES and InChIs

SMILES:
Fc1c([C@@]2(OCC(C2)COc2ccc(N3CCN(CC3)c3ccc(n4c(=O)n(nc4)[C@H]([C@@H](O)C)CC)cc3)cc2)Cn2ncnc2)ccc(F)c1
Canonical SMILES:
CC[C@H](n1ncn(c1=O)c1ccc(cc1)N1CCN(CC1)c1ccc(cc1)OCC1CO[C@@](C1)(Cn1cncn1)c1ccc(cc1F)F)[C@@H](O)C
InChI:
InChI=1S/C37H42F2N8O4/c1-3-35(26(2)48)47-36(49)46(25-42-47)31-7-5-29(6-8-31)43-14-16-44(17-15-43)30-9-11-32(12-10-30)50-20-27-19-37(51-21-27,22-45-24-40-23-41-45)33-13-4-28(38)18-34(33)39/h4-13,18,23-27,35,48H,3,14-17,19-22H2,1-2H3/t26-,27?,35-,37-/m0/s1
InChIKey:
RAGOYPUPXAKGKH-AGDNISCASA-N

Cite this record

CBID:1131 http://www.chembase.cn/molecule-1131.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
4-{4-[4-(4-{[(5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-1-[(2S,3S)-2-hydroxypentan-3-yl]-4,5-dihydro-1H-1,2,4-triazol-5-one
IUPAC Traditional name
posaconazole
@posaconazole
Brand Name
Noxafil
Synonyms
4-{4-[4-(4-{[(5''R'')-5-(2,4-difluorophenyl)-5-(1''H''-1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-1-[(2''S'',3''S'')-2-hydroxypentan-3-yl]-4,5-dihydro-1''H''-1,2,4-triazol-5-one
posaconazole
Posaconazole
CAS Number
171228-49-2
PubChem SID
160964594
46508639
PubChem CID
147912
CHEBI ID
64355
ATC CODE
J02AC04
CHEMBL
1397
Chemspider ID
130409
DrugBank ID
DB01263
KEGG ID
D02555
Unique Ingredient Identifier
6TK1G07BHZ
Wikipedia Title
Posaconazole
Medline Plus
a607036

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID Price

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem ALOGPS 2.1
Acid pKa 14.826501  H Acceptors
H Donor LogD (pH = 5.5) 5.394681 
LogD (pH = 7.4) 5.4060388  Log P 5.406185 
Molar Refractivity 200.7058 cm3 Polarizability 70.79972 Å3
Polar Surface Area 111.79 Å2 Rotatable Bonds 12 
Lipinski's Rule of Five false 
Log P 4.71  LOG S -4.77 
Solubility (Water) 1.20e-02 g/l 

PROPERTIES

PROPERTIES

Physical Property Pharmacology Properties Bioassay(PubChem)
Solubility
Insoluble expand Show data source
Hydrophobicity(logP)
5.5 expand Show data source
Admin Routes
Oral expand Show data source
Bioavailability
High expand Show data source
Excretion
Fecal (77%) and renal (14%) expand Show data source
Half Life
16 to 31 hours expand Show data source
Metabolism
Hepatic glucuronidation expand Show data source
Protein Bound
98 to 99% expand Show data source
Legal Status
Rx-only (US) expand Show data source
Pregnancy Category
B3 (Australia) expand Show data source
C (US) expand Show data source
US Licence
Posaconazole expand Show data source
EU Licence
Noxafil expand Show data source

DETAILS

DETAILS

DrugBank DrugBank Wikipedia Wikipedia
DrugBank - DB01263 external link
Item Information
Drug Groups approved; investigational
Description Posaconazole is a triazole antifungal drug that is used to treat invasive infections by Candida species and Aspergillus species in severely immunocompromised patients.
Indication For prophylaxis of invasive Aspergillus and Candida infections in patients, 13 years of age and older, who are at high risk of developing these infections due to being severely immunocompromised as a result of procedures such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD), or due to hematologic malignancies with prolonged neutropenia from chemotherapy. Also for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole. Posaconazole is used as an alternative treatment for invasive aspergillosis, Fusarium infections, and zygomycosis in patients who are intolerant of, or whose disease is refractory to, other antifungals.
Pharmacology Posaconazole is an antifungal agent structurally related to itraconazole. It is a drug derived from itraconzaole through the replacement of the chlorine substituents with flourine in the phenyl ring, as well as hydroxylation of the triazolone side chain. These modifications enhance the potency and spectrum of activity of the drug. Posaconazole can be either fungicial or fungistatic in action.
Toxicity During the clinical trials, some patients received posaconazole up to 1600 mg/day with no adverse events noted that were different from the lower doses. In addition, accidental overdose was noted in one patient who took 1200 mg BID for 3 days. No related adverse events were noted by the investigator.
Affected Organisms
Aspergillis, Candida and other fungi
Biotransformation Posaconazole primarily circulates as the parent compound in plasma. Of the circulating metabolites, the majority are glucuronide conjugates formed via UDP glucuronidation (phase 2 enzymes). Posaconazole does not have any major circulating oxidative (CYP450 mediated) metabolites. The excreted metabolites in urine and feces account for ~17% of the administered radiolabeled dose.
Absorption Posaconazole is absorbed with a median Tmax of approximately 3 to 5 hours.
Half Life Posaconazole is eliminated with a mean half-life (t½) of 35 hours (range 20 to 66 hours).
Protein Binding Posaconazole is highly protein bound (>98%), predominantly to albumin.
Elimination The excreted metabolites in urine and feces account for ~17% of the administered radiolabeled dose.
Distribution * 1774 L
Clearance * 32 L/hr
* 51 L/hr [Single-Dose Suspension Administration of 200 mg, fasted]
* 21 L/hr [Single-Dose Suspension Administration of 200 mg, nonfat meal]
* 14 L/hr [Single-Dose Suspension Administration of 200 mg, high fat meal]
* 91 L/hr [Single-Dose Suspension Administration of 400 mg, fasted]
* 43 L/hr [Single-Dose Suspension Administration of 400 mg with liquid nutritional supplement (14 g fat)]
References
Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, Helfgott D, Holowiecki J, Stockelberg D, Goh YT, Petrini M, Hardalo C, Suresh R, Angulo-Gonzalez D: Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007 Jan 25;356(4):348-59. [Pubmed]
Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, Greinix H, Morais de Azevedo W, Reddy V, Boparai N, Pedicone L, Patino H, Durrant S: Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007 Jan 25;356(4):335-47. [Pubmed]
Bhattacharya M, Rajeshwari K, Dhingra B: Posaconazole. J Postgrad Med. 2010 Apr-Jun;56(2):163-7. [Pubmed]
Frampton JE, Scott LJ: Posaconazole : a review of its use in the prophylaxis of invasive fungal infections. Drugs. 2008;68(7):993-1016. [Pubmed]
Schiller DS, Fung HB: Posaconazole: an extended-spectrum triazole antifungal agent. Clin Ther. 2007 Sep;29(9):1862-86. [Pubmed]
Kwon DS, Mylonakis E: Posaconazole: a new broad-spectrum antifungal agent. Expert Opin Pharmacother. 2007 Jun;8(8):1167-78. [Pubmed]
Groll AH, Walsh TJ: Posaconazole: clinical pharmacology and potential for management of fungal infections. Expert Rev Anti Infect Ther. 2005 Aug;3(4):467-87. [Pubmed]
Rachwalski EJ, Wieczorkiewicz JT, Scheetz MH: Posaconazole: an oral triazole with an extended spectrum of activity. Ann Pharmacother. 2008 Oct;42(10):1429-38. Epub 2008 Aug 19. [Pubmed]
Li Y, Theuretzbacher U, Clancy CJ, Nguyen MH, Derendorf H: Pharmacokinetic/pharmacodynamic profile of posaconazole. Clin Pharmacokinet. 2010 Jun;49(6):379-96. doi: 10.2165/11319340-000000000-00000. [Pubmed]
External Links
Wikipedia
RxList
Drugs.com

REFERENCES

REFERENCES

From Suppliers Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • • Frampton JE, Scott LJ: Posaconazole : a review of its use in the prophylaxis of invasive fungal infections. Drugs. 2008;68(7):993-1016. Pubmed
  • • Schiller DS, Fung HB: Posaconazole: an extended-spectrum triazole antifungal agent. Clin Ther. 2007 Sep;29(9):1862-86. Pubmed
  • • Kwon DS, Mylonakis E: Posaconazole: a new broad-spectrum antifungal agent. Expert Opin Pharmacother. 2007 Jun;8(8):1167-78. Pubmed
  • • Groll AH, Walsh TJ: Posaconazole: clinical pharmacology and potential for management of fungal infections. Expert Rev Anti Infect Ther. 2005 Aug;3(4):467-87. Pubmed
  • • Rachwalski EJ, Wieczorkiewicz JT, Scheetz MH: Posaconazole: an oral triazole with an extended spectrum of activity. Ann Pharmacother. 2008 Oct;42(10):1429-38. Epub 2008 Aug 19. Pubmed
  • • Li Y, Theuretzbacher U, Clancy CJ, Nguyen MH, Derendorf H: Pharmacokinetic/pharmacodynamic profile of posaconazole. Clin Pharmacokinet. 2010 Jun;49(6):379-96. doi: 10.2165/11319340-000000000-00000. Pubmed
  • • Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, Helfgott D, Holowiecki J, Stockelberg D, Goh YT, Petrini M, Hardalo C, Suresh R, Angulo-Gonzalez D: Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007 Jan 25;356(4):348-59. Pubmed
  • • Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, Greinix H, Morais de Azevedo W, Reddy V, Boparai N, Pedicone L, Patino H, Durrant S: Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007 Jan 25;356(4):335-47. Pubmed
  • • Bhattacharya M, Rajeshwari K, Dhingra B: Posaconazole. J Postgrad Med. 2010 Apr-Jun;56(2):163-7. Pubmed
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