Synthesis and evaluation of trimetoquinol derivatives: Novel thromboxane A2/prostaglandin H2 antagonists with diminished β-adrenergic agonist activity

Journal of Medicinal Chemistry

Volumn 40, Issue 1, 1997, Pages 85-91

  Christoff, Jeffrey J ^a,c   Bradley, Luke ^a   Miller, Duane D ^b   Lei, Longping ^a   Rodriguez, Fernando ^a   Fraundorfer, Paul ^a   Romstedt, Karl ^a   Shams, Gamal ^a   Feller, Dennis R ^a  

^a OHIO STATE UNIVERSITY   (United States)

^b UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^c MIDWESTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6,7 DIHYDROXY 1 (4 HYDROXY 3 NITROBENZYL) 1,2,3,4 TETRAHYDROISOQUINOLINE; PROSTAGLANDIN H2; PROSTAGLANDIN H2 RECEPTOR BLOCKING AGENT; THROMBOXANE A2 RECEPTOR BLOCKING AGENT; TRETOQUINOL; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BETA ADRENERGIC RECEPTOR BLOCKING; CATECHOLAMINE SYNTHESIS; DRUG POTENCY; DRUG STRUCTURE; GUINEA PIG; HUMAN; HUMAN CELL; HUMAN TISSUE; MALE; NONHUMAN; PROSTAGLANDIN SYNTHESIS INHIBITION; STRUCTURE ACTIVITY RELATION;

ADRENERGIC BETA-AGONISTS; ANIMALS; BINDING SITES; GUINEA PIGS; HUMANS; PLATELET AGGREGATION; PROSTAGLANDIN H2; PROSTAGLANDINS H; RECEPTORS, PROSTAGLANDIN; RECEPTORS, THROMBOXANE A2, PROSTAGLANDIN H2; STEREOISOMERISM; THROMBOXANE A2; TRETOQUINOL;

EID: 0031023358     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm950896w     Document Type: Article

References (21)

1. Iwasawa, Y.; Kiyomoto, A. Studies on Tetrahydroisoquinolines (THI) (I) Bronchodilator Activity and Structure-Activity Relationships. Jpn. J. Pharmacol. 1967, 17, 143-152.
2. Shtachner, G.; Crowley, H. J.; Dalton, C. Inhibition of Platelet Aggregation by Papaverine-Like Drugs: Evidence for a Novel Mechanism of Action. Biochem. Pharmacol. 1976, 25, 1045-1050.
3. Kiyomoto, A.; Sato, M.; Nagao, T.; Nakajima, H. Studies on Tetrahydroisoquinolines (THI) (VII): Effect of Trimetoquinol on the Cardiovascular System. Eur. J. Pharmacol. 1969, 5, 303-312.
4. Feller, D. R.; Venkatramen, R.; Miller, D. D. Comparative Actions of Trimetoquinol, Tetrahydropapaverine, and Salsinol Isomers in Beta-Adrenoceptors. Biochem. Pharmacol. 1975, 24, 1357-1359.
5. Dalton, C.; Crowley, H. J.; Czyzewski, L. B. Trimethoquinol-Different Pharmacological Properties of Optical Isomers. Biochem. Pharmacol. 1976, 25, 2209-2210.
6. Mayo, J. R.; Navaran, S. S.; Akbar, H.; Miller, D. D.; Feller, D. R. Stereo-Dependent Inhibition of Human Platelet Function by the Optical Isomers of Trimetoquinol. Biochem. Pharmacol. 1981, 30, 2237-2241.
7. Ahn, C.; Romstedt, K. J.; Wallace, L. J.; Miller, D. D.; Feller, D. R. Characterization of the Inhibition of U46619-Mediated Human Platelet Activation by the Trimetoquinol Isomers. Biochem. Pharmacol. 1988, 37, 3023-3033.
8. 2 Receptor Sites. Thromb. Res. 1988, 50, 387-399.
9. Adejare, A.; Miller, D. D.; Fedyna, J. S.; Ahn, C.; Feller, D. R. Syntheses and β-Adrenergic Agonist and Antiaggregatory Properties of N-Substituted Trimetoquinol Analogues. J. Med. Chem. 1986, 29 (9), 1603-1609.
10. Fedyna, J. S.; Adejare, A.; Miller, D. D.; Feller, D. R. Pharmacological Evaluation of the β-Adrenoceptor Agonist and Thromboxane Antagonist Properties of N-Substituted Trimetoquinol Analogues. Eur. J. Pharmacol. 1987, 135, 161-171.
11. 2 Antagonist Activity of N-Benzyltrimetoquinol Analogues. J. Med. Chem. 1988, 31 (8), 1506-1512.
12. Shams, G.; Harrold, M. W.; Grazyl, B.; Miller, D. D.; Feller, D. R. Pharmacological Evaluation of the β-Adrenoceptor Agonist Properties of N-Benzyl Substituted Trimetoquinol Analogues. Eur. J. Pharmacol. 1990, 184, 251-256.
13. 2 Antagonists. Drug Des. Delivery 1987, 1, 193-207.
14. Shams, G.; Romstedt, K. J.; Gerhardt, M. A.; Harrold, M. W.; Miller, D. D.; Feller, D. R. Pharmacological Evaluation of the β-Adrenoceptor Agonist and Thromboxane Receptor Blocking Properties of 1-Benzyl Substituted Trimetoquinol Analogues. Eur. J. Pharmacol. 1990, 184, 21-31.
15. Fraundorfer, P.; Fertel, R. H.; Miller, D. D.; Feller, D. R. Biochemical and Pharmacological Characterization of high Affinity Trimetoquinol Analogs on Guinea Pig and Human Beta-adrenergic Subtypes: Evidence for Partial Agonism. J. Pharmacol. Exp. Ther. 1994, 270, 665-674.
16. 2/ Prostaglandin H2 Receptors in Human Platelets, Rat Vasular Endothelial Cells, and Rat Vascular Smooth Muscle Cells. J. Pharmacol. Exp. Therp. 1993, 267, 1017-1023.
17. 2 by polar groupings. J. Med. Chem. 1972, 15 (2), 200-201.
18. White, R. L., Jr.; Schwan, T. J.; Alaimo, R. J. Rearrangement of a Pyranone to a Benzothiazole. J. Heterocycl. Chem. 1980, 17, 817-818.
19. 2/Prostaglandin H2 Receptors in Platelets and Blood Vessels: Evidence for Different Receptors. J. Pharmacol. Exp. Ther. 1985, 233, 418-424.
20. Huzoor-Akbar; Romstedt, K.; Manhire, B. Computerized Aggregation Instrument: A Highly Efficient and Versatile System for Acquisition, Quantitation, Presentation and Management for Platelet Aggregation Data. Thromb. Res. 1983, 32, 335-341.
21. 2/prostaglandin H2 receptors in human platelets. J. Pharmacol. Exp. Ther. 1988, 245, 786-792.