Chromones asthma

Perhaps one of the most effective agents currently available for the treatment of the bronchial spasms attendant to asthma is a synthetic agent that incorporates the chromone moiety. 

The discovery of the utility of the bis-chromone carboxylic acid derivative cromolyn sodium in the treatment of asthma and related allergies has led to an intensive, and thus far not very fruitful, effort to discover analogues which would show oral activity in contrast to the lead which must be administered by inhalation. Preparation of a typical analogue, proxicromil (63), starts with the O-allylated phenol 57. Claisen rearrangement leads to the corresponding C-allylated product 58. 

Cromolyn sodium (Intal) and nedocromil sodium (Tilade) are chemically related drugs called chromones that are used for the prophylaxis of mild or moderate asthma. Both are administered by inhalation and have... 

In the bischromone (169), which is valuable in the treatment of asthma, the two chromone moieties are inclined at about 53° to each other. Furthermore, the carboxyl groups lie in the plane of the chromone rings, whilst the central hydroxyl group is directed away from the chromone ring planes (7UPS1458,74MI22204). 

Methylesculetol-6,7-dinicotinate (32) is useful as an antiinflammatory and vasodilator oflow toxicity (101). The synthesis of asarone [5555-15-1] (2,4,5-trimethoxy-l-propenylbenzene), which is used as a tranquilizer, has been patented (102). It occurs in calamus root, Acorns calamus L.y and is a chemosterilant for insects (103). 6,7-Dihydroxycoumarin-4-methylsulfonic acid and its salts are useful in the treatment of capillary permeability and fragility and for protecting oxidizable metabolites and drugs against biooxidation (104). Certain chromones derived from hydroxyhydroquinone, eg (33), and its salts, esters, and amides are valuable in the prophylactic treatment of asthma (105) (see Antiasthmatic agents). 2-Methoxy-6-multiprenyl-l,4-benzoquinones are intermediates in the microbiological synthesis of coenzyme Q compounds (106). 

The red, violet, and blue pigments of flower petals are called anthocyanins, and are glycosides of various benzopyrilium cations. Delphinidin chloride 9.7, for example, is a blue pigment. Khellin 9.8 is a natural product which has found clinical application in the treatment of bronchial asthma and has been the starting point for the design of many totally synthetic chromones with improved biological properties. 

Other examples of twin drugs are the antioxidant probucol, which lowers the cholesterol level in blood, and cromolyn, a chromone heterocycle, which is useful in the inhalational treatment of bronchial asthma (Fig. 1.11). 

Nedocromil is a chromone analogue also used by inhalation as an aerosol, primarily in the prophylaxis of asthma and reversible obstructive airway disease. It inhibits release of allergic mediators, and it is effective in a broad range of patients. An ophthalmic solution is available for the treatment of seasonal and perennial allergic conjunctivitis. Other structurally related compounds are not currently available in the United States but are available in other markets. 

New, Orally Effective Chromone Derivatives for the Treatment of Asthma... 

At that time we considered our stock data on anti-asthmatic compounds from experimental asthma studies in humans. Thus, we knew that mono- and bischromones were highly active by inhalation, but that none of the compounds which we had prepared up to that time were orally effective. This lack of oral activity was, we decided, due to the high polarity and low lipophilic character of the chromone derivatives that we had prepared up to that time. For example, cromolyn had a pKa of about 1.5 and an octanol/water (pH 7.4 aqueous buffer) log D value of about -3.5. Such a compound would be expected to have a very poor absorption profile. This was reflected in its short plasma half-life following intravenous administration and the fact that its plasma levels following oral administration in a number of species were extremely low ( ). 

AEROSOLS ASTHMA/DRUG THY CHROMONES/THER USE CLINICAL RESEARCH DISODIUM CtlROMOGLYCATE/ADV EFF iHUMAN PLACEBOS... 

ASTHMA/IMMUNOL CHROMONES/THER USE iCLINICAL RESEARCH DISODIUM CROMOGLYCATE/THER USE HUMAN PASSIVE CUTANEOUS ANAPHY PLACEBOS... 

ASTHMA/DRUG THY CHROMONES/THER USE DISODIUM CROMOGLYCATE/ THER USE HUMAN INHALAT10N THERAPY lSOPROTERENOL/THER USE RESPIRATORY FUNCTION TES SKIN TESTS... 

ANIMAL EXPERIMENTS ASTHMA/DRUG THY CHILD CHROMONES/THER USE DISODIUM CROMOGLYCATE/THER USE GAMMA GLOBULIN/THER USE GUINEA PIGS HISTAMINE/PHYSIOLY HUMAN RATS SEROTONIN/ PHYSIOLY ... 

Immunological Aspects - In the past year, the immunologic approach to asthma therapy has centered around clinical studies employing dlsodlum cromoglycate (III), a chromone derivative whose pharmacology was initially... 

Derivatives of benzopyran-4-one, commonly known as chromones (I), are an important class of compounds because of their pharmacological significance [1], and one of the derivatives, disodium cromoglycate (II) [2] is at present in clinical use for allergic bronchial asthma- Chromones containing... 

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