Prenalterol Explained

Prenalterol, sold under the brand name Hyprenan, is a sympathomimetic agent and cardiac stimulant which acts as a β₁-adrenergic receptor partial agonist and is used in the treatment of heart failure.^{[1] [2] [3] [4] [5]} It has selectivity for the β₁-adrenergic receptor. Its partial agonist activity or intrinsic sympathomimetic activity is about 60%.^[6] It is said to have much greater impact on myocardial contractility than on heart rate. The drug has been marketed in Denmark, Norway, and Sweden.

Chemistry

Synthesis

Stereospecific

Prenalterol exhibits adrenergic agonist activity in spite of an interposed oxymethylene group. The stereospecific synthesis devised for this molecule relies on the fact that the side chain is very similar in oxidation state to that of a sugar.^{[7] [8]}

Condensation of monobenzone (2) with the epoxide derived from α-D-glucofuranose^[9] affords the glycosylated derivative (3). Hydrolytic removal of the acetonide protecting groups^[10] followed by cleavage of the sugar with periodate gives aldehyde (4). This is reduced to the glycol by means of NaBH₄ and the terminal alcohol is converted to the mesylate (5). Displacement of the leaving group with isopropylamine followed by hydrogenolytic removal of the O-benzyl ether affords the β₁-adrenergic selective adrenergic agonist prenalterol (6).

Racemic

Several preparations of the racemic mixture have been reported.^{[11] [12] [13] [14] [15]}

See also

• Alifedrine
• Xamoterol

Further reading

• Special Issue on Prenalterol . 10.1111/joim.1982.211.issue-s659. 1982. Acta Medica Scandinavica. 211. S659.

Notes and References

1. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies . Springer US . 2014 . 978-1-4757-2085-3 . 2024-08-29 . 1014.
2. Book: Schweizerischer Apotheker-Verein . Index Nominum 2000: International Drug Directory . Medpharm Scientific Publishers . Index nominum . 2000 . 978-3-88763-075-1 . 29 August 2024 . 873.
3. Book: Morton IK, Hall JM . Concise Dictionary of Pharmacological Agents: Properties and Synonyms . Springer Netherlands . 2012 . 978-94-011-4439-1 . 2024-08-29 . 231.
4. Kendall MJ, Goodfellow RM, Westerling S . Prenalterol--a new cardioselective inotropic agent . J Clin Hosp Pharm . 7 . 2 . 107–118 . June 1982 . 7050180 . 10.1111/j.1365-2710.1982.tb01010.x . free .
5. Hadfield SE, Slee SJ, Snow HM . The cardiovascular pharmacology of xamoterol, cicloprolol, prenalterol and pindolol in the anaesthetised dog . British Journal of Clinical Pharmacology . 28 . Suppl 1 . 78S–81S . 1989 . 2572262 . 1379883 . 10.1111/j.1365-2125.1989.tb03580.x .
6. Wirtzfeld A, Klein G, Bibra HV, Sauer E . Prenalterol: a partial beta 1-adrenoceptor agonist or a beta-blocker with intrinsic activity? . Int J Clin Pharmacol Ther Toxicol . 23 . 1 . 20–27 . January 1985 . 2859252 .
7. DE. 2503968. 1975-08-14. Optisch aktive Derivate des 1-Phenoxy-2-hydroxy-3-aminopropan und Verfahren zu ihrer Herstellung [Optically active derivatives of 1-phenoxy-2-hydroxy-3-aminopropane and the process for their production]. Ciba-Geigy AG. Jaeggi KA, Schröter H, Ostermayer F . Chem. Abstr. 84, 5322 (1976).
8. corresp to and (1975, 1976, 1977, all to Ciba-Geigy)
9. Web site: Α-D-Glucofuranose | C6H12O6 . ChemSpider.
10. Liu Z, Hu BH, Messersmith PB . Acetonide Protection of Dopamine for the Synthesis of Highly Pure N-docosahexaenoyldopamine . Tetrahedron Letters . 51 . 18 . 2403–2405 . May 2010 . 20543896 . 2882309 . 10.1016/j.tetlet.2010.02.089 .
11. NL. 6409883. H. Köppe et al.
12. (1965, 1972 both to Boehringer Ingelheim)
13. NL. 301580. A. F. Crowther, L. H. Smith
14. (1965, 1970 both to ICI)
15. Crowther AF, Gilman DJ, McLoughlin BJ, Smith LH, Turner RW, Wood TM . Beta-Adrenergic blocking agents. V. 1-Amino-3-(substituted phenoxy)-2-propanols . Journal of Medicinal Chemistry . 12 . 4 . 638–642 . July 1969 . 5793156 . 10.1021/jm00304a018 .