Description
Isoetharine is a direct-acting sympathomimetic with relatively low selectivity with
β2-adrenoreceptors. However, it quickly calms bronchospasms better than more selective
bronchodilators.
Originator
Dilabron,Sterling Winthrop
Definition
ChEBI: Isoetharine is a catecholamine.
Manufacturing Process
36 g 3,4dibenzyl-hydroxy-butyrophenone was dissolved in 125 ml methylene
chloride and 16 g bromine was added dropwise after 15 g calcium carbonate.
An obtained precipitate was filtered off. The filtrate was distilled to dryness to
give 1-(3,4-dibenzyloxy-phenyl)-2-bromo-butan-1-one. It was dissolved in a
portion of ethanol and 15 g of isopropylamine was added. The mixture had
stood for night at room temperature and thereafter ether was added. The
isopropylamine hydrobromide had fallen. It was filtered off, the filtrate was
shook with 200 ml of diluted hydrochloric acid. At that 4-(1-hydroxy-2-
isopropylamino-butyl)-benzene-1,2-diol chlorohydrate was separated as an oil.
The oil was diluted with the 5 volumes of ethanol and the calculated quantity
hydrogen was passed through in a presence of palladium on coal catalyst. The
catalyst was filtered off and a solvent was removed to dryness, the residue
had crystallized by grinding with acetone. The obtained 4-(1-hydroxy-2-
isopropylamino-butyl)-benzene-1,2-diol chlorohydrate was recrystallized from
methanol. MP: 212°-213°C. Chlorohydrate may be changed into isoetharine
with the calculated quantity of any base.
Brand name
Bronk ometer (Sanofi Aventis).
Therapeutic Function
Sympathomimetic, Bronchodilator
General Description
Isoetharine was the first 2-selectivedrug widely used for the treatment of airway obstruction.However, its degree of selectivity and activity for 2-receptors may not approach that of some of the other agentssuch as terbutaline, albuterol, or even ISO. Because of thepresence of the β2-directing β-ethyl group and -directingisopropyl group, isoetharine is a β2-agonist and is resistantto MAO. However, because it contains the catechol ringsystem, it is metabolized by COMT and O-sulfated quiteeffectively. Consequently, it has a short DOA similar to thatof ISO and is used only by inhalation for the treatment ofacute episodes of bronchoconstriction.
Clinical Use
The clinical use of isoetharine is declining
because of its low β2 specificity, but it is still
used in combinations.
Synthesis
Isoetharine, 3,4-dihydroxy-|á-[1-(iso-propylamino)propyl]benzylic alcohol
(11.1.11), differs from isoproterenol in the presence of an additional ethyl group in the ethylamino side chain?aand is synthesized by bromination of 3,4-dibenzyloxybutyrophenone and
the subsequent reaction of the resulting bromo derivative (11.1.9) with isopropylamine. The
product (11.1.10) undergoes reduction by hydrogen using a palladium catalyst, during which
the carbonyl group is simultaneously reduced and the benzyl-protecting group is removed,
forming isoetharine (11.1.11) [15].
