Intal Compound

Proprietary Names. Aleudrin(e) Ingelan Iso-Autohaler Medihaler Iso Norisodrine. It is an ingredient of Intal Compound. 

Pattenden and coworkers have recently evaluated the relative merits of LTA and electrochemical oxidation of phenolic compounds with particular reference to synthesis of the antiallergic compounds sodium chromoglycate (INTAL 53) and proxicromil (54), which are used for the prophylactic treatment of asthma. The 2-carboxychromone moieties in the compounds (53) and (54) are synthesized from the appropriate 2, 6 -dihydroxyacetophenones. Oxidation of the 2 -hydroxyacetophenone (55) by LTA in cU-chloromethane gave almost exclusively the quinol acetate (56), which was subsequently converted to the 2, 6 -dihydroxyacetophenone (57), a precursor to proxicromil (54 Scheme 21). By contrast, electro-... 

Chemotherapeutically valuable compounds in this group are a series of coumarins, of which Acenocoumarol is one, which are valuable as anticoagulants, and Intal, which is used in the treatment of bronchial asthma. One of the earliest optical brighteners was 7-diethylamino-4-methylcoumarin. ... 

It is now more than ten years since Fisons, U.K. introduced the compound Intal, cromolyn sodium, or disodium cromoglycate as it will be referred to in this introduction, as an effective agent for the prophylaxis of asthma in man. This introduction caused considerable excitement and activity in the rest of the pharmaceutical industry as well as in academic medical circles. There were several reasons for this interest but one of the most important was that cromoglycate appeared to be a drug with a completely novel mode of action in asthma therapy. 

The antiallergy activity of the pyrimido[4,5-b]quinolines was determined using the 48-hour IgE-mediated rat passive cutaneous anaphylaxis (PCA) procedure (6,2), which is widely used as a screen to identify agents with a pharmacological profile similar to intal. The compounds were administered to groups of 5 to 7 rats either intravenously in saline at pH 7.2-8.0 or orally in an aqueous solution near physiological pH (fi). Since these compounds did not demonstrate antagonism toward the anaphylactic mediators, histamine and serotonin, their activity is an indication of inhibition of mediator release. 

The reaction sequence described in the foregoing section was used to synthesize compounds which are up to 400 times more potent intravenously than Intal and 10 times more potent orally than the parent pyrimido[4,5-b]quinoline ester. Figures 5-10 depict the effects of substituent variation on activity in the PCA procedure. 

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