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Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEMBL', 'StdInChI', 'StdInChIKey', 'CAS_number').
 
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{{Short description|Chemical compound}}
{{Orphan|date=February 2011}}
{{Drugbox
{{Drugbox
| Verifiedfields = changed
⚫
| IUPAC_name = 2-[Bis(2-chloroethyl)amino]-4-hydroxy-2''H''1,3,2-oxazaphosphinan-2-one
| verifiedrevid = 457654634
| image = 4hydroxycyclophosphamide.png
⚫
| IUPAC_name = (2''S'',4''S'')-''N'',''N''-Bis(2-chloroethyl)-4-hydroperoxy-2-oxo-1,3,2λ<sup>5</sup>-oxazaphosphinan-2-amine
⚫
| width =
| image = 4-hydroperoxycyclophosphamide.svg
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| width = 125
| alt =
| alt =
| image2 =
| drug_name =
| width2 =
| imagename = <!-- else may use drug_name -->
| drug_name = <!-- else may use imagename -->


<!--Clinical data-->
<!-- Clinical data -->
| tradename =
| tradename =
| licence_EU = <!-- EMA requires brand name -->
| licence_US = <!-- FDA may use generic name -->
| DailyMedID = <!-- preference to licence_US -->
| DailyMedID = <!-- preference to licence_US -->
⚫
| legal_status =
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
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| dependency_liability =
| pregnancy_US = <!-- A / B / C / D / X -->
| routes_of_administration = Extracorporal treatment of cellular masses; [[Intravenous therapy|intravenously]]
| pregnancy_category =
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
⚫
| legal_status =
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| dependency_liability =
| routes_of_administration =


<!--Pharmacokinetic data-->
<!-- Pharmacokinetic data -->
| bioavailability =
| bioavailability =
| protein_bound =
| protein_bound =
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| excretion =
| excretion =


<!--Identifiers-->
<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct}}
| CAS_number = <!-- blanked - oldvalue: 40277-05-2 -->
| CAS_number = 39800-16-3
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = U880A4FUDA
| CAS_supplemental =
| CAS_supplemental =
| ATCvet =
| ATCvet =
| ATC_prefix = <!-- 'none' if uncategorised -->
| ATC_prefix = L01
| ATC_suffix =
| ATC_suffix =
| ATC_supplemental =
| ATC_supplemental =
| PubChem =
| PubChem = 38347
| PubChemSubstance =
| PubChemSubstance =
| IUPHAR_ligand =
| IUPHAR_ligand =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =
| ChemSpiderID =
| DrugBank =
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChEMBL = <!-- blanked - oldvalue: 731 -->
| synonyms =
| ChemSpiderID = 35147
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 61511
| ChEBI = 196991
| ChEBI_Ref = {{ebicite|correct|EBI}}
| synonyms = Perfosfamide


<!--Chemical data-->
<!-- Chemical data -->
| C=7 | H=15 | Cl=2 | N=2 | O=4 | P=1
| chemical_formula =
⚫
| smiles = C1COP(=O)(NC1OO)N(CCCl)CCCl
| C=7 | H=15 | Ag= | As= | Au= | B= | Bi= | Br= | Cl=2 | Co= | F= | Fe= | Gd= | I= | K= | Mn= | N=2 | Na= | O=3 | P=1 | Pt= | S= | C= | Se= | Sr= | Tc= | charge =
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| molecular_weight =
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| StdInChI = 1S/C7H15Cl2N2O4P/c8-2-4-11(5-3-9)16(13)10-7(15-12)1-6-14-16/h7,12H,1-6H2,(H,10,13)/t7-,16-/m0/s1
⚫
| smiles = OC1CCOP(=O)(N1)N(CCCl)CCCl
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
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| StdInChI = <!-- blanked - oldvalue: InChI=1S/C7H15Cl2N2O3P/c8-2-4-11(5-3-9)15(13)10-7(12)1-6-14-15/h7,12H,1-6H2,(H,10,13) -->
| StdInChIKey = <!-- blanked - oldvalue: RANONBLIHMVXAJ-UHFFFAOYSA-N -->
| StdInChIKey = VPAWVRUHMJVRHU-GYKQLYQFSA-N
| density =
| density =
| melting_point =
| melting_point =
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}}
}}


'''Perfosfamide''', or '''4-hydroperoxycyclophosphamide''' (trade name '''Pergamid''') was an experimental drug candidate for blood cancers that was rejected by the FDA in 1993 and never reached the market.
'''4-Hydroxycyclophosphamide''' is the main, [[active]] [[metabolite]] of [[cyclophosphamide]].<ref>{{cite journal | doi = 10.1021/ja00803a070 | last1 = Van Der Steen | first1 = J. | last2 = Timmer | first2 = E. C. | last3 = Westra | first3 = J. G. | last4 = Benckhuysen | first4 = C. | title = 4-Hydroperoxidation in the Fenton oxidation of the antitumor agent cyclophosphamide | journal = [[J. Am. Chem. Soc.]] | volume = 95 | pages = 7535 | year = 1973}}</ref><ref>{{cite journal | doi = 10.1006/abio.1995.1021 | last1 = Wright | first1 = JE | last2 = Tretyakov | first2 = O | last3 = Ayash | first3 = LJ | last4 = Elias | first4 = A | last5 = Rosowsky | first5 = A | last6 = Frei E | first6 = 3rd | title = Analysis of 4-hydroxycyclophosphamide in human blood | journal = Analyt. Biochem. | volume = 224 | issue = 1 | pages = 154–158 | year = 1995 | pmid = 7710063}}</ref>


==References==
==Intended use==
Perfosfamide was used experimentally by oncologists in the 1980s for use in [[bone marrow transplant]] procedures for treatment of blood cancers. It was added to the tissue after it had been taken from the donor but before the tissue was administered to the patient to "purge" [[lymphocyte]]s in order to prevent [[GVHD|Graft Versus Host Disease]], which results from donor lymphocytes attacking normal host cells and tissues, and to "purge" a patient's own (autologous) collected [[hematopoietic stem cells]] of any [[malignant cell]]s it may still contain at the time of harvesting.<ref>{{cite journal | vauthors = Sládek NE | title = Aldehyde dehydrogenase-mediated cellular relative insensitivity to the oxazaphosphorines | journal = Current Pharmaceutical Design | volume = 5 | issue = 8 | pages = 607–25 | date = August 1999 | doi = 10.2174/1381612805666230110215319 | pmid = 10469894 }}</ref><ref>{{cite book | vauthors = Colvinn OM | chapter = Chapter 20: Pharmacologic Purging of Bone Marrow. | title = Thomas' Hematopoietic Cell Transplantation | volume = 457 | veditors = Thomas ED, etal | publisher = John Wiley & Sons | date = 2004 | isbn = 9781405112567 }}</ref>{{rp|255}}

In 1989 Nova Pharmaceutical took over development of the compound and in 1992, it submitted a [[new drug application]] to the FDA for using perfosamide to purge malignant cells in transplants for the treatment of [[acute myeloid leukemia]]. In the ensuing year, it merged with Scios to become Scios Nova. In March 1993, the FDA's Oncology Drugs Advisory Committee rejected the application because all the data was from the experimental uses, and no [[randomized clinical trial]] had been conducted.<ref>{{cite journal | first = Jeffrey L. | last = Fox | name-list-style = vanc | title = Scios Nova may purge Pergamid after FDA setback. | journal = Nature Biotechnology | date = April 1993 | volume = 11 | issue = 4 | pages = 439 | doi = 10.1038/nbt0493-439 | s2cid = 6110616 }}</ref> At the review meeting, Scios Nova also announced that it would not fund further development of the drug candidate.<ref>{{cite web | work = The Pink Sheet | date = 8 March 1993 | url = https://www.pharmamedtechbi.com/publications/the-pink-sheet/55/010/scios-novas-pergamid-no-further-trials-will-be-funded | title = Scios Nova's Pergamid: No Further Trials Will Be Funded }}</ref>

==Chemistry==
Perfosfamide is an oxazaphosphorine compound, similar to [[mafosfamide]] and [[cyclophosphamide]]. Like those compounds it, is metabolized to [[4-hydroxycyclophosphamide]], which eventually gives rise to the two directly cytotoxic metabolites — [[phosphoramide mustard]] and [[acrolein]].<ref>{{cite journal | vauthors = Ludeman SM | title = The chemistry of the metabolites of cyclophosphamide | journal = Current Pharmaceutical Design | volume = 5 | issue = 8 | pages = 627–43 | date = August 1999 | doi = 10.2174/1381612805666230110215458 | pmid = 10469895 }}</ref>

== References ==
{{reflist}}
{{reflist}}


{{Chemotherapeutic agents}}
{{Chemotherapeutic agents}}


[[Category:Abandoned drugs]]
{{DEFAULTSORT:Hydroxycyclophosphamide, 4-}}
[[Category:Organochlorides]]
[[Category:Organochlorides]]
[[Category:IARC Group 1 carcinogens]]
[[Category:Alkylating antineoplastic agents]]
[[Category:Oxazaphosphinans]]
[[Category:Oxazaphosphinans]]
[[Category:Nitrogen mustards]]
[[Category:Nitrogen mustards]]
[[Category:Phosphorodiamidates]]
[[Category:Phosphorodiamidates]]
[[Category:Organic peroxides]]

[[Category:Chloroethyl compounds]]
[[pt:4-Hidroxiciclofosfamida]]
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