Antagonists leukotrienes

Oxo-4//-pyrido[],2-n]pyrimidin-2-yl]oxymethylsaccharin derivatives 418 exhibited human leukocyta elastase inhibitory activities (94EUP626378, 95USP5378720). 2-Substituted 4//-pyrido[l, 2-n]pyrimidin-4-one (419) is a potent human leukocyta elastase inhibitors (A", 1.79/xM) (96USP5512576). The 4//-pyrido[l,2-n]pyrimidin-4-one moiety was included in leukotriene antagonist 2-ethynylthiazole derivatives (98JAP(K) 98/195063)... 

Salmon, J.A. and Garland, G. (1991). Leukotriene antagonists and inhibitors of leukotriene biosynthesis as potential therapeutic agents. Prog. Drug Res. 37, 9-73. 

Findlay, S.R., Barden, J.M., Easley, C.B. and Glass, M. (1992). Effect of the oral leukotriene antagonist ICI 204,219 on the antgen-induced bronchoconstriction in subjects with asthma. J. Allergy Clin. Immunol. 89, 1040-1045. 

For example, (Ipc)2BCl was found to be an advantageous in the enantioselective reduction in the large-scale preparation of L-699,392, a specific leukotriene antagonist of interest in the treatment of asthma.147... 

Patients receiving these agents may notice improvement in 1 to 2 weeks, but maximal benefit may not be seen for 4 to 6 weeks. Cromolyn and nedocromil appear to be similar in efficacy to the leukotriene antagonists and theophylline for persistent asthma.18 Both agents are well tolerated with adverse effects limited to cough and wheezing. Bad taste and headache have also been reported with nedocromil. One dose of cromolyn or nedocromil prior to exercise or allergen exposure will provide effective prophylaxis for 1 to 2 hours. Cromolyn and nedocromil are not as effective as albuterol for prophylaxis of exercise-induced asthma. 

Holgate ST, Bradding P, Sampson AP. Leukotriene antagonists and synthesis inhibitors new directions in asthma therapy. J Allergy Clin Immunol 1996 98 1-13. 

Antiasthmatics Bronchodilators Anti-inflammatories Leukotriene antagonists... 

Although leukotriene antagonists represent a new therapeutic alternative, published studies to date have shown them to be no more effective than peripherally selective antihistamines and less effective than intranasal corticosteroids. However, combined use with antihistamines is more effective than antihistamine treatment alone. 

Sustained-release theophylline is less effective than inhaled corticosteroids and no more effective than oral sustained-release /J2-agonists, cromolyn, or leukotriene antagonists. 

Anderson, W., et al., "A Single Nucleotide Polymorphism in the 5-Lipoxygenase Gene is Associated with a Reduced Response to Leukotriene Antagonists," Am. Rev. Respir. Crit. Care Med., 163(5), A198 (2000). 

Currie GP, Lima JJ, Sylvester JE, Lee DK, Cockburn WJ, Lipworth BJ. (2003) Leukotriene C4 synthase polymorphisms and responsiveness to leukotriene antagonists in asthma. Br J Clin Pharmacol. 56, 422-426. 

Leukotriene antagonist Tetrazolyl-aromatic thioethers 89EUP298583... 

Leukotriene antagonist Tetrazolyl-2-quinolinyl methoxy aryl ethers 90JMC1186... 

There is no role for other anti-inflammatory drugs such as sodium cromoglycate, nedocromil, keto-tifen, leukotriene antagonists or antihistamines in COPD. 

Table 3.4 Measured and calculated log P values (Clog P) of leukotriene antagonists ...

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