Antiasthmatic activity

A group at Lilly reported that phenoxazine (89) is a potent inhibitor of cRBL (0.02 iM) [237]. Substitution at the 1-position by carboxylic acid, ester, or hydroxamic acid groups decreased potency 10- to 30-fold. Substitution at the 2-position was less destructive of inhibition as long as the substituent was lipophilic (ester, acrylate ester) carboxylate caused a 200-fold loss of potency. Activity in rat neutrophils has been disclosed for related structures in patents from Bayer [238]. The second aromatic ring is not required, as shown by the activity of series exemplified by (90)-(92) [239-242]. Antiasthmatic activity was indicated for these compounds, but few details were given. 

Intramolecular cyclization of azide (141) was acheived by heating in toluene for 72 h (75% yield). Subsequent deprotection of the protecting groups with TFA afforded the fused tetrazole (142) [95TL7511], The tetrazole (144) was formed from 143 by reaction with NaN, in HC1, AcOH and H20 compound possessed antiasthmatic activity [95CPB683],... 

ONO 3708 is a prostaglandin derivative, a (thromboxane TP) PROSTANOID RECEPTOR ANTAGONIST. It has experimental hepatoprotective properties, ontazolast [usan] (BIRM 270) is a pyridlnyl-benzoxazolamine derivative, a lipoxygenase inhibitor with potential antiasthmatic activity,... 

The noradrenaline analogue (I) shown in Fig. 8.10 has useful antiasthmatic activity, but it is of short duration due to its rapid metabolism to the inactive methyl ether (II). 

The toxicity of astemizole also appears to be remarkably low. An acute toxicity study in rats found that at 25,000 times the antihistaminic dose (2,560 mg/kg) the drug produced some transient sedation but no lethality up to 2 weeks after administration—an extreme safety margin. This raises the possibility that antihistamines may have intrinsic antiasthmatic activity, but at such doses that the toxicity of the first-generation drugs precluded such a use at safe doses. 

Konno, S., Asano, K., Kurokawa, M., Ikeda, K., Okamoto, K., and Adachi, K. (1994). Antiasthmatic activity of a macrolide antibiotic, roxithromycin Analysis of possible mechanisms in vitro and in vivo. Int. Arch. Allergy Immunol. 105, 308-316. 

C7H8N4O2, Mr 180.17, thin, bitter-tasting platelets, mp. 270-274 °C (monohydrate), moderately soluble in water, very soluble in hot water, alkali hydroxides, ammonia, dilute acids. A purine alkaloid from the leaves of the tea plant, also contained in matd (Ilex paragua-riensis and Paullinia cupana). The methylxanthines T., caffein(e), and theobromine are among the oldest known stimulants and drugs. Their pharmacological properties are compared in the table. In high doses T. can cause epilepsy-like convulsions. T. also exhibits antiasthmatic activity. ... 

A rarer type of simple phenols with C Cx structures are known as acetophenones. Some of these have demonstrated antiasthmatic activity, particularly apocynin and its glycoside androsin, which are derived from Picrorhiza kurroa (Dorsch et al. 1994). 

The Chapman rearrangement has been exploited in the synthesis of compounds that possess potent antiasthmatic activity. In particnlar, imidazo[4,5-c]quinolin-4(5//)-one derivatives (44) underwent reactions that were shown to proceed via an nnnsual thermally promoted rearrangement, wherein the methyl gronp at N-1 migrates to N-3 with concomitant Chapman rearrangement (Scheme 18.7) [25]. 

The use of metered-dose valves in aerosol medical appHcations permits an exact dosage of an active dmg to be deHvered to the respiratory system where it can act locally or be systemicaHy absorbed. For example, inhalers prescribed for asthmatics produce a fine mist that can penetrate into the bronchial tubes (see Antiasthmatic agents). 

The chromone cromolyn sodium (5-5) was at one time considered the forerunner of a novel class of antiallergic and antiasthmatic drugs that act at one of the earliest stages of the allergic reaction. Detailed experiments, acmally conducted after the dmg s clinical effectiveness had been confirmed, suggested that the compound inhibited the release of mediators of the allergic reaction from mast cells. The dmg is not very active when taken orally and is usually applied topically to the lung by insufflation as its sodium salt. Considerable efforts to uncover additional structurally related mediator release inhibitors have had only limited success. 

Cassia occidentalis L. C. torosa Cav. Wang Jiang Nan (Coffee senna, sicklepod) (seed, root) Anthraquinones, torosachrysone, n-methylmorpholine, apigenin, galactomannan, cassiollin, xanthorin, dianthronic heteroside, helminthosporin.4-33 496 Mild purgative, lower blood pressure, antioxidative, antiasthmatic, antitoxic, antimalarial, antibacterial, anthraquinones and hepatoprotective activities. 

ML-3000 ((2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)-acetic acid) is a nonantioxidant dual inhibitor of both cyclooxygenase and 5-lipoxygenase. ML-3000 has been compared to indomethacin in a number of experimental models of inflammation. The analgesic effects of ML-3000 have also been assessed in a number of animal models. Phase II studies have shown a wide range of activities, including anti-inflammatory, analgesic, antiplatelet and antiasthmatic properties (Laufer et al., 1994 Chin and Wallace, 1999). 

Thienotriazolodiazepines derivatives, (I), were initially prepared by Braquet (1) in a 11-step synthetic process and were effective as platelet-activating factor inhibitors and used as antiasthmatic, antiallergic, and gastrointestinal protects. 

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