Design and discovery of RWJ 22108 - A novel bronchoselective calcium channel blocker

Drug Design and Discovery

Volumn 15, Issue 3, 1998, Pages 135-148

  Dodd, John H ^a   Schwender, Charles F ^a   Moore Jr , John B ^a   Ritchie, David M ^a   Gray Nunez, Yolanda ^a   Loughney, Deborah ^a   Kirchner, Thomas ^a   Miller, William C ^a   Mockoviak, Sandra ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

Asthma; Bronchodilator; Bronchoselective; Calcium antagonist; Dihydropyridine

Indexed keywords

9 (2 CHLORO 6 FLUOROPHENYL) 2,3,4,5,6,9 HEXAHYDRO 7 METHYL 1,1 DIOXOTHIACYCLOHEPTENO[3,2 B]PYRIDINE 8 CARBOXYLIC ACID 2 (N BENZYL N METHYLAMINO)ETHYL ESTER; ANTIASTHMATIC AGENT; CALCIUM CHANNEL BLOCKING AGENT; SULFONE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AORTA; ARTICLE; CONTROLLED STUDY; DRUG DESIGN; DRUG POTENCY; DRUG STRUCTURE; FEMALE; INHALATIONAL DRUG ADMINISTRATION; NONHUMAN; TRACHEA;

ANIMALS; ANTI-ASTHMATIC AGENTS; AORTA, THORACIC; BINDING, COMPETITIVE; BLOOD PRESSURE; BRONCHI; CALCIUM CHANNEL BLOCKERS; CHEMISTRY, PHYSICAL; DOGS; DRUG DESIGN; FEMALE; MODELS, MOLECULAR; NITRENDIPINE; ORGAN SPECIFICITY; PYRIDINES; RABBITS; STRUCTURE-ACTIVITY RELATIONSHIP; TRACHEA;

EID: 0031864343     PISSN: 10559612     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (34)

1. Dodd, J. H., Schwender, C. F., Conley, R. A., Moore, J. B., Ritchie, D. M., Fabian, A. C., Fenk, C. J., Bourcet, E., Gray-Nunez, Y., Kirchner, T., Henneman-Webster, R. R., Lindabery, G. C., Miller, W. C., Mockoviak, S and Stefanick, S. M. (1993). Synthesis and Biological Properties of RWJ 22108, a Bronchoselective Calcium Channel Blocker, Drug Des. Discovery, 10, 65-75.
2. Marin, J. (1988). Vascular Effects of Calcium Antagonists Uses in Some Cerebrovascular Disorders, Gen. Pharmacol., 19, 295-306.
3. Rafferty, P., Varley, J. G., Edwards, J. S. and Holgate, S. T. (1987) Inhibition of Exercise-Induced Asthma by Nifedipine: A Dose-Response Study, Br. J. Clin. Pharmacol., 24, 479-484.
4. Kivity, S., Gannem, R., Greif, J., Sneh, E., Struhar, D. and Topilsky, M. (1985). The Synergistic Effect of Chromolin Sodium (CS) and Nifedipine (N) on Airway Hyperreactivity (AH), Ann. Allergy, 55, 255.
5. Ozenne, G., Moore, N. D., Leprevost. A., Tardif, C., Boismare, F., Pasquis, P and Lemercier, J.-P. (1985). Nifedipine in Chronic Bronchial Asthma: a Randomized DoubleBlind Crossover Trial Against Placebo, Eur. J. Respir. Dis., 67, 238-243.
6. Massey, K. L., Hendeles, L., Harman, E., Hill, M. and Peeler, D. (1986). The Effect of Increasing Doses of Inhaled Gallopamil (G) on Airway Reactivity to Methacholine in Intermittent Asthmatics,. Allergy Clin. Immunol., 77, 152.
7. Patel, K. R. and Tullett, W. M. (1985). Comparison of Two Calcium Antagonists, Verapamil and Gallopamil (D-600), in Exercise-Induced Asthma, Eur. J. Respir. Dis., 67, 269-271.
8. Gianotti, A., Bottino, G and Moscatelli. P. (1987). Some Effects of Prolonged Treatment with Nicardipine in Chronic Bronchial Asthma, Curr. Med. Res. Opin., 10, 422-426.
9. Ando, F., Quattrone, G., Molonia, N., Girbino, G., Capillo, G., Barberio, G., Pajno, G. B. and Ruggeri, C. (1988). Effect of Verapamil in Methacoline Induced Bronchoconstriction in Children, Eur Respir. J., 1, 165s.
10. Sene, L., Boner, A. L. and Vallone, G. (1986). Effect of Two Different Doses of Calcium Antagonist Verapamil on Methacholine Induced Bronchoconstriction in Children with Bronchial Asthma, Ann. Allergy, 56, 516.
11. Ferrari, M., Olivieri, M., De Gasperi, M. and Lechi, A. (1989). Differential Effects of Nifedipine and Diltiazem on Methacholine-Induced Bronchospasm in Allergic Asthma, Ann. Allergy, 63, 196-200.
12. Rodger, I. W. (1988). Calcium Ion Mechanisms in Airway Smooth Muscle: Potential Targets for Novel Symptomatic Drugs for Asthma, Agents Actions Suppl , 23, 69-87.
13. Mulloy, E. M., Cormie, P., Harvey, J. and Marley, J. E. (1990). Nitrendipine Therapy in Asthmatic Subjects, Br J. Clin. Pharmacol., 30, 493-495.
14. Ghosh, S. K. and Rafferty, P. (1991). Effect of Felodipine on Histamine and Adenosine Induced Bronchoconstriction in Patients with Asthma, Eur. J. Clin., Pharmacol., 41, 73-74.
15. Patel, K. R. and Kerr, J. W. (1982). Calcium Antagonists in Experimental Asthma, Clin. Allergy, 12(suppl.), 15-20.
16. Patel, K. R. (1981). The Effect of Verapamil on Histamine and Methacholine-Induced Bronchoconstriction, Clin. Allergy, 11, 441 -447.
17. So, S. Y., Larn, W. K. and Yu, D. Y. C. (1982). Effect of Calcium Antagonists on Allergen-Induced Asthma, Clin. Allergy, 12, 595-600.
18. Patel, K. R. and Al-Shamma, M. (1982). Effect of Nifedipine on Histamine Reactivity in Asthma, Br. Med. J., 284, 1916.
19. Patel, K. R. (1981). Calcium Antagonists in Exercise-Induced Asthma, Br. Med J., 282, 932-933.
20. So, S. Y , Ip, M. and Larn, W. K. (1986). Calcium Channel Blockers and Asthma, Lung, 164, 1-16.
21. Mathews, K P. (1983). Cutaneous Anaphylactoid and Anaphylactic Reactions, N. Engl. Reg. Allergy Proc., 4, 41-48.
22. Freedman, D. D. and Waters, D. D. (1987). 'Second Generation' Dihydropyridine Calcium Antagonists. Greater Vascular Selectivity and Some Unique Applications, Drugs, 34, 578-598
23. Langs, D. A., Strong, P. D. and Triggle, D. J. (1990). Receptor Model for the Molecular Basis of Tissue Selectivity of 1,4-Dihydropyridine Calcium Channel Drugs, J. Comput Aided Mol. Des., 4, 215-230.
24. Dodd, J. H., Schwender, C. F. and Gray-Nunez, Y. (1990). Synthesis of Novel Cyclic Sulfone Dihydropyridines Facilitated by a Selective Ethyl Diazoacetate Ring Expansion, J. Heterocycl. Chem., 27, 1453-1456
25. ++ Channel Asonist Bay K 8644, J. Pharmacol. Exp. Ther., 231. 8-15.
26. Himori, N. and Tiara, N. (1980) Differential Effects of the Calcium Antagonistic Vasodilators, Nifedipine and Verapamil. on the Tracheal Musculature and Vasculature of the Dog, Br. J. Pharmacol., 68, 595-597.
27. Triggle, A. M., Shefter, E. and Triggle, D J. Crystal Structures of Calcium Channel Antagonists: 2, 6-Dimethyl-3, 5-dicarbomethoxy-4-[2-nitro-, 3-cyano-, 4-(dimethylamino)-, and 2, 3, 4, 5, 6-pentafluorophenyl]-1, 4-dihydropyridine, J. Med. Chem., 23. 1442-1445. 10a. SYBYL version 6.3 beta, Tripos Associates, St. Louis, Missouri. 10b. Cambridge Crystallographic Database version 5.12, Cambridge Crystallographic Data Centre, Cambridge, England.
28. Triggle, A. M., Shefter, E. and Triggle, D J. Crystal Structures of Calcium Channel Antagonists: 2, 6-Dimethyl-3, 5-dicarbomethoxy-4-[2-nitro-, 3-cyano-, 4-(dimethylamino)-, and 2, 3, 4, 5, 6-pentafluorophenyl]-1, 4-dihydropyridine, J. Med. Chem., 23. 1442-1445. 10a. SYBYL version 6.3 beta, Tripos Associates, St. Louis, Missouri. 10b. Cambridge Crystallographic Database version 5.12, Cambridge Crystallographic Data Centre, Cambridge, England.
29. Triggle, A. M., Shefter, E. and Triggle, D J. Crystal Structures of Calcium Channel Antagonists: 2, 6-Dimethyl-3, 5-dicarbomethoxy-4-[2-nitro-, 3-cyano-, 4-(dimethylamino)-, and 2, 3, 4, 5, 6-pentafluorophenyl]-1, 4-dihydropyridine, J. Med. Chem., 23. 1442-1445. 10a. SYBYL version 6.3 beta, Tripos Associates, St. Louis, Missouri. 10b. Cambridge Crystallographic Database version 5.12, Cambridge Crystallographic Data Centre, Cambridge, England.
30. Okamoto, K. and Aoki, K. (1963). Development of a Strain of Spontaneously Hypertensive Rats, Jpn. Circ. J., 27, 282-293.
31. van Zwieten, P A., van Meel, J. C. A. and Timmermans, P. B. M. W. M. (1983) Pharmacology of Calcium Entry Blockers: Interaction with Vascular Alpha-Andrenoceptors, Hypertens., 5(suppl. II), II8-II17.
32. Ritchie, D M., Kirchner, T., Moore, J. B., Dodd, J. H., Ahmed, T., Andersen, D. W. and Capetola, R. J. (1992). Experimental Antiasthmatic Activity of RWJ 22108. A Bronchoselective Calcium Entry Blocker, Int Arch. Allergy. Immunol , 100. 274-282
33. Schwender, C. F. and Dodd, J. H. (1989). Preparation of Thiocycloalkeno [3, 2-B] pyridines, US 4, 879, 384, Chem. Abstr., (1990) 112, 198354r.
34. (1983). 2-Hydroxyethyl methyl 2, 6-dimethyl-4-(3-nitrophenyl)-1, 4-dihydropyridine-3, 5-dicarboxylate, JP 58, 201, 764, Chem. Abstr , (1984) 100. 138968m.