Metabolites of the angiotensin II antagonist tasosartan: The importance of a second acidic group

Journal of Medicinal Chemistry

Volumn 41, Issue 22, 1998, Pages 4251-4260

  Ellingboe, John W ^a   Collini, Michael D ^a   Quagliato, Dominick ^a   Chen, James ^a   Antane, Madelene ^a   Schmid, Jean ^a   Hartupee, Dale ^a   White, Valerie ^a   Park, C Hyung ^a   Tanikella, Tarak ^a   Bagli, Jehan F ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 DEOXY 1 [5 [4' (7 OXO 6,7 DIHYDRO 5H PYRIDO[2,3 D] PYRIMIDIN 8 YLMETHYL) BIPHENYL 2 YL] TETRAZOL 2 YL] BETA DEXTRO GLUTARIC ACID; 2 BUTYL 4 CHLORO 1 [[2' (1H TETRAZOL 5 YL) 4 BIPHENYLYL]METHYL] 5 IMIDAZOLECARBOXYLIC ACID; 2,4 DIMETHYL 5 HYDROXY 8 [2' (1H TETRAZO 5 YL)BIPHENYL 4 YLMETHYL 8H PYRIDO[2,3 D]PYRIMIDINE 7 ONE; 2,4 DIMETHYL 8 [2' (1H TETRAZOL 5 YL) BIPHENYL 4 YLMETHYL] 8H PYRIDO[2,3 D]PYRIMIDIN 7 ONE; 5 HYDROXY 2,4 DIMETHYL 8 [2' (1H TETRAZOL 5 YL) BIPHENYL 4 YLMETHYL] 6,8 DIHYDRO 5H PYRIDO[2,3 D]PYRIMIDINE 7 ONE SESQUIHYDRATE; ANGIOTENSIN RECEPTOR; CANDESARTAN; ELISARTAN; LOSARTAN; TASOSARTAN; UNCLASSIFIED DRUG; ZOLASARTAN;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIHYPERTENSIVE ACTIVITY; ARTICLE; BLOOD PRESSURE REGULATION; DRUG RECEPTOR BINDING; HYPERTENSION; MALE; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM;

ADMINISTRATION, ORAL; ADRENAL GLANDS; ANGIOTENSIN II; ANIMALS; BLOOD PRESSURE; HEART RATE; HYPERTENSION; INJECTIONS, INTRAVENOUS; LIVER; MODELS, MOLECULAR; MOLECULAR CONFORMATION; PYRIDONES; PYRIMIDINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTOR, ANGIOTENSIN, TYPE 1; RECEPTOR, ANGIOTENSIN, TYPE 2; RECEPTORS, ANGIOTENSIN; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAZOLES;

EID: 15144353434     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970690q     Document Type: Article

References (16)

1. Ferrarro, C. M. The Renin-Angiotensis System: Importance in Physiology and Pathology. J. Cardiovasc. Pharmacol. 1990, 15 (Suppl. 3), S1-S5.
2. McAreavey, D. Robertson, J. I. S. Angiotensin converting enzyme inhibitors and moderate hypertension. Drugs 1990, 40, 326-345.
3. Greenlee, W. J. Renin Inhibitors. Med. Res. Rev. 1990, 10, 173-236.
4. Wexler, R. R.; Greenlee, W. J.; Irvin, J. D.; Goldberg, M. R.; Prendergast, K.; Smith, R. D.; Timmermans, P. B. W. M. Nonpeptide Angiotensin II Receptor Antagonists: The Next Generation in Antihypertensive Therapy. J. Med. Chem. 1996, 39, 625-656.
5. Judd, D. B.; Dowle, M. D.; Middlemiss, D.; Scopes, D. I. C.; Ross, B. C.; Jack, T. I.; Pass, M.; Tranquillini, E.; Hobson, J. E.; Panchal, T. A.; Stuart, P. G.; Paton, J. M. S.; Hubbard, T.; Hilditch, A.; Drew, G. M.; Robertson, M. J.; Clark, K. L.; Travers, A.; Donnelly, M. D.; Walker, D. G.; Richards, S. A. Bromobenzofuran-Based Non-peptide Antagonists of Angiotensin II: GR138950, a Potent Antihypertensive Agent with High Oral Bioavailability. J. Med. Chem. 1994, 37, 3108-3120.
6. Mealy, N.; Castaner, J. Elisartan Potassium. Drugs of the Future, 1996, 21, 139-142.
7. Kubo, K.; Kohara, Y.; Imamiya, E.; Sigiura, Y.; Inada, Y.; Furukawa, Y.; Nishikawa, K.; Naka, T. Nonpeptide angiotensin II receptor antagonists. Synthesis and biological activity of benzimidazolecarboxylic acids. J. Med. Chem. 1993, 36, 2182-2195.
8. Stearns, R. A.; Miller, R. R.; Doss, G. A.; Chakravarty, P. K.; Rosegay, A.; Gatto, G. J.; Chiu, S.-H. L. The Metabolism of DuP753, a Nonpeptide Angiotensin II Receptor Antagonist, by Rat, Monkey, and Human Liver Slices. Drug Metab. Dispos. 1992, 20, 281-287.
9. Sweet, C. S.; Nelson, E. B. How well have animal studies with losartan predicted responses in humans. J. Hypertens. 1993, 11 (Suppl. 3), S63-S67.
10. Wong, P. C.; Price, W. A.; Chiu, A. T.; Duncia, J. V.; Carini, D. J.; Wexler, R. R.; Johnson, A. L.; Timmermans, P. B. W. M. Nonpeptide Angiotensin II Receptor Antagonists. XI. Pharmacology of EXP3174: An Active Metabolite of DuP 753, An Orally Active Antihypertensive Agent. J. Pharmacol. Exp. Ther. 1990, 255, 211-217.
11. Ellingboe, J. W.; Antane, M.; Nguyen, T. T.; Collini, M. D.; Antane, S.; Bender, R.; Hartupee, D.; White, V.; McCallum, J.; Park, C. H.; Russo, A.; Osler, M.; Wojdan, A.; Dinish, J.; Ho, D. M.; Bagli, J. F. Pyrido[2,3-d]pyrimidine Angiotensin II Antagonists. J. Med. Chem. 1994, 37, 542-550.
12. Hultin, T. A.; Lihotz, L. A.; Scatina, J. Comparative Metabolism of Tasosartan in Mice, Rats, Dogs and Monkeys. Int. Soc. Study Xenobiotics Proc. 1997, 11, 226.
13. Sakamoto, T.; Kondo, Y.; Yamanaka, H. Studies on Pyrimidine Derivatives. XXVIII. Synthesis of Pyridopyrimidine Derivatives by Cross-coupling of Halopyrimidines with Olefins and Acetylenes. Chem. Pharm. Bull. 1982, 30, 2410-2416.
14. 1 subtype, G protein coupled receptor. Chem. Biol. 1994, 1, 211-221.
15. Prendergast, K.; Adams, K.; Greenlee, W. J.; Nachbar, R. B.; Patchett, A. A.; Underwood, D. J. Derivation of a 3D pharmacophore model for the angiotensin-II site one receptor. J. Comput.-Aided Mol. Des. 1994, 8, 491-512.
16. Sybyl, v6.4, Tripos Associates, St. Louis, Missouri.