isoetarine

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

Uses

Isoetharine is used in treating chronic obstructive illnesses of outer respiratory tract.

Uses

Bronchodilator.

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 chainaand 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].