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Bucindolol

From Wikipedia, the free encyclopedia
Chemical compound

Pharmaceutical compound
Bucindolol
Clinical data
ATC code
  • none
Identifiers
  • 2-[2-hydroxy-3-[[2-(1H-indol-3-yl)-1,1-dimethyl-ethyl]amino]propoxy]benzonitrile
CAS Number
PubChemCID
ChemSpider
UNII
ChEMBL
CompTox Dashboard(EPA)
ECHA InfoCard100.114.291Edit this at Wikidata
Chemical and physical data
FormulaC22H25N3O2
Molar mass363.461 g·mol−1
3D model (JSmol)
  • N#Cc0ccccc0OCC(O)CNC(C)(C)Cc1c[nH]c2c1cccc2

Bucindolol is anon-selectivebeta blocker with additional weakalpha-blocking properties andintrinsic sympathomimetic activity in some model systems[1][2] but not in human hearts.[3][4] It was under review by theFDA in theUnited States for the treatment ofheart failure in 2009, but was rejected due to issues pertaining to integrity of data submitted.[5]

Synthesis

[edit]

The displacement of the dimethylamino group ingramine (1) by the anion from2-nitropropane gives 3-(2-methyl-2-nitropropyl)indole (2), which isreduced to theamine alpha,alpha-dimethyltryptamine (3). Separately, the reaction of 2-hydroxybenzonitrile (4) withepichlorohydrin gives theepoxide (5). Combination of the two intermediates (3) and (5) gives bucindolol.[6][7]

See also

[edit]

References

[edit]
  1. ^Reinhart KM, White CM (June 2009)."Bucindolol: a beta-blocker for the treatment of heart failure".Formulary.44 (6): 166. Archived fromthe original on 2012-03-04.
  2. ^Willette RN, Mitchell MP, Ohlstein EH, Lukas MA, Ruffolo RR (January 1998). "Evaluation of intrinsic sympathomimetic activity of bucindolol and carvedilol in rat heart".Pharmacology.56 (1):30–36.doi:10.1159/000028179.PMID 9467185.S2CID 46848815.
  3. ^Bristow MR, Roden RL, Lowes BD, Gilbert EM, Eichhorn EJ (December 1998)."The role of third-generation beta-blocking agents in chronic heart failure".Clinical Cardiology.21 (12 Suppl 1): I3-13.doi:10.1002/clc.4960211303.PMC 6656140.PMID 9853189.
  4. ^Hershberger RE, Wynn JR, Sundberg L, Bristow MR (June 1990). "Mechanism of action of bucindolol in human ventricular myocardium".Journal of Cardiovascular Pharmacology.15 (6):959–967.doi:10.1097/00005344-199006000-00014.PMID 1694919.
  5. ^Husten L (2 June 2009)."FDA rejects bucindolol and questions trial integrity".CardioBrief.
  6. ^US 4234595, Kreighbaum WE, Comer WT, "3-Indolyl-tertiary butylaminopropanols", issued 18 November 1980, assigned to Mead Johnson & Company 
  7. ^Kreighbaum WE, Matier WL, Dennis RD, Minielli JL, Deitchman D, Perhach JL, et al. (March 1980). "Antihypertensive indole derivatives of phenoxypropanolamines with beta-adrenergic receptor antagonist and vasodilating activity".Journal of Medicinal Chemistry.23 (3):285–289.doi:10.1021/jm00177a015.PMID 6102605.
Sympatholytic (and closely related)antihypertensives (C02)
Sympatholytics
(antagonizeα-adrenergic
vasoconstriction)
Central
α2-Adrenergic receptor agonists
Adrenergic release inhibitors
Imidazoline receptor agonists
Ganglion-blocking/nicotinic antagonists
Peripheral
Indirect
Monoamine oxidase inhibitors
VMAT inhibitors
Tyrosine hydroxylase inhibitors
Direct
α1-Adrenergic receptor blockers
Non-selective α-adrenergic receptor blockers
Otherantagonists
Serotonin receptor antagonists
Endothelin receptor antagonists (forPHTooltip Pulmonary hypertension)
α1
Agonists
Antagonists
α2
Agonists
Antagonists
β
Agonists
Antagonists
Tryptamines
4-Hydroxytryptamines
andesters/ethers
5-Hydroxy- and
5-methoxytryptamines
N-Acetyltryptamines
α-Alkyltryptamines
α-Ketotryptamines
Cyclized tryptamines
Isotryptamines
Related compounds
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