propyphenazone
{{short description|Chemical compound}}
{{Drugbox
| IUPAC_name = 1,5-Dimethyl-2-phenyl-4-propan-2-yl-pyrazol-3-one
| image = Propyphenazone-2d-skeletal.png
| image_class = skin-invert-image
| width = 180
| tradename =
| Drugs.com = {{drugs.com|international|propyphenazone}}
| pregnancy_category =
| legal_status =
| routes_of_administration = Oral
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 479-92-5
| ATC_prefix = N02
| ATC_suffix = BB04
| ATC_supplemental =
| PubChem = 3778
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 3646
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = OED8FV75PY
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 135538
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 28318
| C=14 | H=18 | N=2 | O=1
| smiles = O=C1C(C(C)C)=C(C)N(C)N1c2ccccc2
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C14H18N2O/c1-10(2)13-11(3)15(4)16(14(13)17)12-8-6-5-7-9-12/h5-10H,1-4H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = PXWLVJLKJGVOKE-UHFFFAOYSA-N
| melting_point =
}}
File:Saridon von Hoffmann-La Roche.jpg, ca. 1950/60]]
Propyphenazone (known as isopropylantipyrine in Japan){{cite web|title=Isopropylantipyrine|url=https://www.drugs.com/international/isopropylantipyrine.html|website=Drugs.com|access-date=8 March 2018}} is a derivative of phenazone{{cite journal | vauthors = Göres E, Kossowicz J, Schneider HG | title = [Propyphenazone. Pharmacology and use] | language = German | journal = Medizinische Monatsschrift für Pharmazeuten | volume = 27 | issue = 3 | pages = 72–6 | date = March 2004 | pmid = 15032249 | trans-title = Propyphenazone. Pharmacology and use }} with similar analgesic and antipyretic effects. Originally patented in 1931,{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=530 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA530 |language=en}} propyphenazone is marketed as a combination formulation with paracetamol and caffeine for treatment of primary headache disorder.{{Cite news|url=https://economictimes.indiatimes.com/industry/healthcare/biotech/pharmaceuticals/sc-exempts-painkiller-saridon-from-the-banned-list-in-india/articleshow/68092873.cms?from=mdr|title=SC exempts painkiller Saridon from the banned list in India|date=February 21, 2019|newspaper=The Economic Times}}
Serious adverse events
Case reports have described acute inferior-wall myocardial infarctions characterized by low atrial rhythms{{vague|date=January 2021}} (Kounis syndrome) secondary to propyphenazone use.{{cite journal | vauthors = Akyel A, Alsancak Y, Yayla Ç, Sahinarslan A, Özdemir M | title = Acute inferior myocardial infarction with low atrial rhythm due to propyphenazone: Kounis syndrome | journal = International Journal of Cardiology | volume = 148 | issue = 3 | pages = 352–3 | date = May 2011 | pmid = 20541820 | doi = 10.1016/j.ijcard.2010.05.038 }}
Excerpt from WHO comments
{{quote|text=Propyphenazone, a pyrazolone derivative with anti-inflammatory, analgesic and antipyretic activity, was introduced in 1951 for the treatment of rheumatic disorders. As it is structurally related to aminophenazone it has been associated with severe blood dyscrasias. However, it cannot be transformed into potentially carcinogenic nitrosamines and has therefore been widely used as a replacement drug for aminophenazone. In certain countries, products containing propyphenazone have now been restricted in their indications, whereas in others they are still available, sometimes as over-the-counter preparations.{{ cite book | title = Consolidated List of Products whose Consumption and/or Sale have been Banned, Withdrawn, Severely Restricted or not Approved by Governments, Twelfth Issue | publisher = Department of Economic and Social Affairs of the United Nations Secretariat | year = 2005 | location = New York | page = 232 | url = https://www.un.org/esa/coordination/CL12.pdf }}}}
Banned
Propyphenazone is banned in some countries including Sri Lanka,{{ cite web | title = Multi-Country Survey On Banned And Restricted Pharmaceuticals | publisher = Health Action International Asia Pacific | date = August 2008 | page = 7 | url = http://www.docstoc.com/docs/69868593/Multi-Country-Survey-on-Banned-Restricted-Drugs--rheumatism}} Malaysia, and Thailand.
Synthesis
:File:Propyphenazone synthesis.svg
Ethyl 2-isopropylacetoacetate (1) and phenylhydrazine (2) are combined to form the pyrazolone ring in the intermediate (3), which is alkylated with methyl iodide to yield propyphenazone.{{cite journal |doi=10.1248/yakushi1881.57.11_953 |doi-access=free |title=Synthese verschiedener Pyrazolonderivate |date=1937 |last1=Sawa |first1=Yoshiro |journal=Yakugaku Zasshi |volume=57 |issue=11 |pages=953–962 |language=DE}}{{cite web |url=https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-16-0228 |work=Pharmaceutical Substances |title=Propyphenazone |publisher=Thieme |access-date=2024-07-17}}
See also
References
{{reflist}}
{{Analgesics}}