Compounds and methods for treating PDE IV-related diseases

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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A61K 3144

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059984287

ABSTRACT:
This invention relates to a method for selecting PDE IV inhibitors which have a salutory therapeutic index, and to compounds having these properties.

REFERENCES:
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Drug Development Research 21:135-142 (1990), Koe et al. Effect of Novel Catechol ether imidazolidinones on Calcium-Independent Phosphodiesterase activity, [.sup.3 H]Rolipram Binding and Reserpine-induced Hypothermia in mice.
Fed. of Eur. Bio. Societies, (1992), vol. 302, No.: 2, 181-184, Souness et al., Effects of solubilization and vanadate/glutathione complex on inhibitor potencies against eosinophil cyclic AMP-specific phosphodiesterase.
P.J. Silver et al., (1990), Low K.sub.m cAMP Phosphodiesterase Isozymes and modulation of Tone in Vascular, Airway and Gastrointestinal Smooth Muscle. pp. 358-365.
Psychopharmacology (1990), 102, 17-20, Schmicchen et al., Close correlation between behavioural response and binding in vivo for inhibitors of the rolipram-sensitive phosphodiesterase.
J. Med. Chem. 1991, 34: 291-298, Saccomano et al., Calcium-Independent Phosphodiesterase Inhibitors as Putative Antidepressants: 3-(Bicycloalkyloxy)-4-methoxypheny]-2-imidazolidinones.
J. Med. Chem. 1991, 34, 86-89, Vinick et al., Nicotinamide Ethers: Novel Inhibitors of Calcium-independent Phosphodiesterase and [.sup.3 H]Rolipram Binding.
Br. J. Pharmacol. (1993), 108, 562-568, Cortijo et al., Investigation into the role of phosphodiesterase IV in bronchorelaxation, including studies with human bronchus.
J. Med. Chem, 1993, 36, 1380-1386, Miyamoto et al., Bronchodilator Activity of Xanthine Derivatives Substituted with Functional Groups at the 1- or 7-Position.
J. Med. Chem. vol. 36, No. 22, Oct. 1993 pp. 3274-3277, XP002084976The Crystal structure, absolute config. And phosphodiesterase inhibitory act. Etc . . . P.W. Baures.
Trends Pharmacol. SCI, col. 12, No. 1, 1991 pp. 19-27, XP002012152, Diff. Modulation of tissue function and therapeutic potential etc.. C.D. Nicholson.
Medline. Abstract & Padiatrie Und Genzgebiete, 1991 30 (4) 327-34, Method in individualized pharm. Of diseases of the digestive and the respiratory system in children, XP002084977, M. L. Tarachowski.

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