Chemistry:Bucindolol
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Bucindolol is a non-selective beta blocker with additional weak alpha-blocking properties and intrinsic sympathomimetic activity in some model systems[1][2] but not in human hearts.[3][4] It was under review by the FDA in the United States for the treatment of heart failure in 2009, but was rejected due to issues pertaining to integrity of data submitted.[5]
Synthesis
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The displacement of the dimethylamino group in gramine (1) by the anion from 2-nitropropane gives 3-(2-methyl-2-nitropropyl)indole (2), which is reduced to the amine alpha,alpha-dimethyltryptamine (3). Separately, the reaction of 2-hydroxybenzonitrile (4) with epichlorohydrin gives the epoxide (5). Combination of the two intermediates (3) and (5) gives bucindolol.[6][7]
See also
References
- ↑ "Bucindolol: a beta-blocker for the treatment of heart failure.". Formulary 44 (6): 166. June 2009. http://formularyjournal.modernmedicine.com/formulary/Modern+Medicine+Now/Bucindolol-A-beta-blocker-for-the-treatment-of-hea/ArticleStandard/Article/detail/601855.
- ↑ "Evaluation of intrinsic sympathomimetic activity of bucindolol and carvedilol in rat heart". Pharmacology 56 (1): 30–36. January 1998. doi:10.1159/000028179. PMID 9467185.
- ↑ "The role of third-generation beta-blocking agents in chronic heart failure". Clinical Cardiology 21 (12 Suppl 1): I3-13. December 1998. doi:10.1002/clc.4960211303. PMID 9853189.
- ↑ "Mechanism of action of bucindolol in human ventricular myocardium". Journal of Cardiovascular Pharmacology 15 (6): 959–967. June 1990. doi:10.1097/00005344-199006000-00014. PMID 1694919.
- ↑ "FDA rejects bucindolol and questions trial integrity". CardioBrief. 2 June 2009. http://cardiobrief.org/2009/06/02/fda-rejects-bucindolol-and-questions-trial-integrity/.
- ↑ Kreighbaum WE, Comer WT, "3-Indolyl-tertiary butylaminopropanols", US patent 4234595, issued 18 November 1980
- ↑ "Antihypertensive indole derivatives of phenoxypropanolamines with beta-adrenergic receptor antagonist and vasodilating activity". Journal of Medicinal Chemistry 23 (3): 285–289. March 1980. doi:10.1021/jm00177a015. PMID 6102605.
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