Befunolol
{{short description|Chemical compound}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| IUPAC_name = (RS)-1-
| image = Befunolol.svg
| width =
| tradename = Benfuran, Bentos, Betaclar, Glauconex
| Drugs.com = {{drugs.com|international|befunolol}}
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| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 39552-01-7
| ATC_prefix = S01
| ATC_suffix = ED06
| PubChem = 2309
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB09013
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2219
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 418546MT3A
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07496
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 153984
| synonyms =
| C=16 | H=21 | N=1 | O=4
| SMILES = O=C(c2oc1c(OCC(O)CNC(C)C)cccc1c2)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C16H21NO4/c1-10(2)17-8-13(19)9-20-14-6-4-5-12-7-15(11(3)18)21-16(12)14/h4-7,10,13,17,19H,8-9H2,1-3H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ZPQPDBIHYCBNIG-UHFFFAOYSA-N
}}
Befunolol (INN) is a beta blocker with intrinsic sympathomimetic activity used in the management of open-angle glaucoma.{{cite journal | vauthors = Reichl S, Müller-Goymann CC | title = The use of a porcine organotypic cornea construct for permeation studies from formulations containing befunolol hydrochloride | journal = International Journal of Pharmaceutics | volume = 250 | issue = 1 | pages = 191–201 | date = January 2003 | pmid = 12480285 | doi = 10.1016/S0378-5173(02)00541-0 }} It also acts as a β adrenoreceptor partial agonist.{{cite journal | vauthors = Koike K, Takayanagi I | title = A beta-adrenergic partial agonist (befunolol) discriminates two different affinity sites | journal = Japanese Journal of Pharmacology | volume = 42 | issue = 2 | pages = 325–328 | date = October 1986 | pmid = 2879061 | doi = 10.1254/jjp.42.325 | doi-access = free }}{{cite journal | vauthors = Takayanagi I, Koike K | title = A beta-adrenoceptor blocking agent, befunolol as a partial agonist in isolated organs | journal = General Pharmacology | volume = 16 | issue = 3 | pages = 265–267 | date = January 1985 | pmid = 2862092 | doi = 10.1016/0306-3623(85)90080-1 }} Befunolol was introduced in Japan in 1983 by Kakenyaku Kako Co. under the trade name Bentos.{{cite book|title=Pharmaceutical Manufacturing Encyclopedia|date=January 14, 2008|publisher=William Andrew Publishing|location=Norwich, N.Y.|isbn=978-0815515265|page=542|edition=3rd revised}}
Synthesis
The first reported synthesis of befunolol in 1974 used a benzofuran derivative (4) with epichlorohydrin and then isopropylamine to add the sidechain which was known to produce beta blockers, by analogy with drugs discovered by Imperial Chemical Industries, such as propanolol.{{cite book| vauthors = Lednicer D |title=Strategies for Organic Drug Synthesis and Design|year=1998|publisher=John Wiley & Sons|location=Canada|isbn=0-471-19657-6|pages=37–41}} The requisite intermediate was synthesized from ortho-vanillin (1) by a condensation reaction with chloroacetone (2) in the presence of potassium hydroxide, giving 2-acetyl-7-methoxybenzofuran (3), which was demethylated using hydrobromic acid.{{cite patent | inventor = Ito K, Ikemoto M, Kimura K, Nakanishi T | title = 2-Substituted-(2-hydroxy-3-lower alkaminopropoxy)-benzofurans | country = US | number = 3853923 | gdate = 1974 | assign = Kakenyaku Kako KK | url = https://patents.google.com/patent/US3853923 }}{{cite journal | vauthors = Nakano J, Mimura M, Hayashida M, Fujii M, Kimura K, Nakanishi T | title = Syntheses of the optical isomers of befunolol.HCl and their beta-adrenergic blocking activities | journal = Chemical & Pharmaceutical Bulletin | volume = 36 | issue = 4 | pages = 1399–1403 | date = April 1988 | pmid = 2901296 | doi = 10.1248/cpb.36.1399 | doi-access = free }}{{cite web |url=https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-02-0016 |title=Befunolol | work = Pharmaceutical Substances |publisher=Georg Thieme Verlag KG |access-date=2024-07-01 }}
References
{{Reflist}}
{{Antiglaucoma preparations and miotics}}
{{Adrenergic receptor modulators}}
Category:Benzofuran ethers at the benzene ring
Category:N-isopropyl-phenoxypropanolamines
{{Antihypertensive-stub}}