Befunolol

Befunolol (INN) is a beta blocker with intrinsic sympathomimetic activity used in the management of open-angle glaucoma.[1] It also acts as a β adrenoreceptor partial agonist.[2][3] Befunolol was introduced in Japan in 1983 by Kakenyaku Kako Co. under the trade name Bentos.[4]

Befunolol
Clinical data
Trade namesBenfuran, Bentos, Betaclar, Glauconex
AHFS/Drugs.comInternational Drug Names
ATC code
Identifiers
  • (RS)-1-{7-[2-hydroxy-3-(propan-2-ylamino)propoxy]- 1-benzofuran-2-yl}ethanone
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC16H21NO4
Molar mass291.347 g·mol−1
3D model (JSmol)
  • O=C(c2oc1c(OCC(O)CNC(C)C)cccc1c2)C
  • InChI=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 Y
  • Key:ZPQPDBIHYCBNIG-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

Synthesis

The condensation between 2-Hydroxy-3-methoxybenzaldehyde (ortho-Vanillin) [148-53-8] (1) and Chloroacetone [78-95-5] (2) in the presence of KOH leads to 2-Acetyl-7-methoxybenzofuran [43071-52-9] (3). Splitting the methyl protecting group with hydrogen bromide leads to 2-Acetyl-7-hydroxybenzofuran [40020-87-9] (4). Treatment with epichlorohydrin [106-89-8] led to 2-Acetyl-7-[(oxiran-2-yl)methoxy]benzofuran [39543-77-6] (5). Opening of the oxirane ring with isopropylamine [75-31-0] completed the synthesis of Befunolol (6).

References
  1. Reichl S, Müller-Goymann CC (January 2003). "The use of a porcine organotypic cornea construct for permeation studies from formulations containing befunolol hydrochloride". International Journal of Pharmaceutics. 250 (1): 191–201. doi:10.1016/S0378-5173(02)00541-0. PMID 12480285.
  2. Koike K, Takayanagi I (October 1986). "A beta-adrenergic partial agonist (befunolol) discriminates two different affinity sites". Japanese Journal of Pharmacology. 42 (2): 325–8. doi:10.1254/jjp.42.325. PMID 2879061.
  3. Takayanagi I, Koike K (January 1985). "A beta-adrenoceptor blocking agent, befunolol as a partial agonist in isolated organs". General Pharmacology. 16 (3): 265–7. doi:10.1016/0306-3623(85)90080-1. PMID 2862092.
  4. Pharmaceutical Manufacturing Encyclopedia (3rd revised ed.). Norwich, N.Y.: William Andrew Publishing. January 14, 2008. p. 542. ISBN 978-0815515265.
  5. Castaer, J.; Blancafort, P.; Weetman, DF; Serradell, MN; Befunolol. Drugs Fut 1981, 6, 10, 601.
  6. Nakano, Jun; Mimura, Mitsuo; Hayashida, Mitsuo; Fujii, Masahiro; Kimura, Kazuhiko; Nakanishi, Teruo (1988). "Syntheses of the optical isomers of befunololHCl and their .BETA.-adrenergic blocking activities.". CHEMICAL & PHARMACEUTICAL BULLETIN 36 (4): 1399–1403. doi:10.1248/cpb.36.1399.
  7. Ohishi, Yoshitaka; Nakanishi, Teruo (1983). "Reaction of epichlorohydrin with hydroxybenzo(b)furan.". CHEMICAL & PHARMACEUTICAL BULLETIN. 31 (10): 3418–3423. doi:10.1248/cpb.31.3418.
  8. DE2223184 idem K Ito, M Ikemoto, K Kimura, T Nakanishi. U.S. patent 3,853,923 (1974 to Kakenyaku Kako Kk).
  9. Japan. Pat., 7441358 (1974); CA, 81, 105258r
  10. Kiyoshi Ito, Masahiko Ikemoto, Kazuhiko Kimura, Teruo Nakanishi, U.S. patent 4,056,626 (1977 to Kakenyaku Kako Co., Ltd.).



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