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. It has selectivity for the β1-adrenergic receptor. Its partial agonist activity or intrinsic sympathomimetic activity is about 60%. 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. Condensation of monobenzone (2) with the epoxide derived from α- D -glucofuranose affords the glycosylated derivative (3). Hydrolytic removal of the acetonide protecting groups 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.