Substituted 2-iminopiperidines as inhibitors of human nitric oxide synthase isoforms

Journal of Medicinal Chemistry

Volumn 41, Issue 1, 1998, Pages 96-101

  Webber, R Keith ^a   Metz, Suzanne ^a   Moore, William M ^a   Connor, Jane R ^a   Currie, Mark G ^a   Fok, Kam F ^a   Hagen, Timothy J ^a   Hansen Jr , Donald W ^a   Jerome, Gina M ^a   Manning, Pamela T ^a   Pitzele, Barnett S ^a   Toth, Mihaly V ^a   Trivedi, Mahima ^a   Zupec, Mark E ^a   Siong Tjoeng, F ^a  

^a MONSANTO COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 IMINOPIPERIDINE DERIVATIVE; NITRIC OXIDE SYNTHASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME INHIBITION; INHIBITION KINETICS; MALE; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; CEREBELLUM; ENDOTHELIUM, VASCULAR; ENZYME INHIBITORS; HUMANS; IMINES; ISOENZYMES; KINETICS; LIPOPOLYSACCHARIDES; MALE; MOLECULAR STRUCTURE; NEURONS; NITRATES; NITRIC OXIDE SYNTHASE; NITRITES; PIPERIDINES; RATS; RATS, INBRED LEW; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 15144355927     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9705059     Document Type: Article

References (19)

1. Moncada, S.; Higgs, E. A. Molecular Mechanisms and Therapeutic Strategies Related to Nitric Oxide. FASEB J. 1995, 9, 1319-1330.
2. Kerwin, J. F. Jr.; Heller, M. The Arginine-Nitric Oxide Pathway: A Target for New Drugs. Med. Res. Rev. 1994,14 (1), 23-74.
3. Griffith, O. W.; Stuehr, D. J. Nitric Oxide Synthases: Properties and Catalytic Mechanism. Annu. Rev. Physiol. 1995, 57, 707-736.
4. Marietta, M. A. Nitric Oxide Synthase Structure and Mechanism. J. Biol Chem. 1993,268, 12231-12234.
5. Knowles, R. G.; Moncada, S. Nitric Oxide Synthases in Mammals. Biochem. J. 1994, 298, 249-258.
6. Kerwin, J. F., Jr.; Lancaster, J. R., Jr.; Feldman, P. L. Nitric Oxide: A New Paradigm for Second Messengers. J. Med. Chem. 1995, 38, 4343-4362.
7. Macdonald, J. E. Nitric Oxide Synthase Inhibitors. Annu. Rep. Med. Chem. 1996, 31, 221-230.
8. Rees, D. D.; Palmer, R. M. J.; Moncada, S. Role of EndotheliumDerived Nitric Oxide in the Regulation of Blood Pressure. Proc. Natl. Acad. Sei. U.SA. 1989, 86, 3375-3378.
9. G-Nitroarginine. Biochemistry 1993, 32, 8512-8517.
10. Marietta, M. A. Approaches toward Selective Inhibition of Nitric Oxide Synthase. J. Med. Chem. 1994, 37, 1899-1907.
11. Moore, W. M.; Webber, R. K; Fok, K. F.; Jerome, G. M.; Connor, J. R.; Manning, P. T.; Wyatt, P. S.; Misko, T. P.; Tjoeng, F. S.; Currie, M. G. 2-Iminopiperidine and Other 2-Iminoazaheterocycles as Potent Inhibitors of Human Nitric Oxide Synthase Isoforms. J. Med. Chem. 1996, 39, 669-672.
12. Freifelder, M.; Mattoon, R. W.; Ng, Y. H. Hydrogénation in the Pyridine Series. II. Catalytic Reduction of 2-Monoalkyl- and 2-Dialkylaminopyridines. J. Org. Chem. 1964, 29, 3730-3732.
13. Moore, W. M.; Webber, R. K; Jerome, G. M.; Tjoeng, F. S.; Misko, T. P.; Currie, M. G. L-N6-(l-Iminoethyl)lysine: A Selective Inhibitor of Inducible Nitric Oxide Synthase. J. Med. Chem. 1994, 37, 3886-3888.
14. Misko, T. P.; Moore, W. M.; Kasten, T. P.; Nickols, G. A.; Corbett, J. A.; Tilton, R. G.; McDaniel, M. L.; Williamson, J. R.; Currie, M. G. Selective Inhibition of the Inducible Nitric Oxide Synthase by Aminoguanidine. Eur. J. Pharm. 1993, 233, 119-125.
15. Misko, T. P.; Schilling, R. J.; Salvemini, D. S.; Moore, W. M.; Currie, M. G. A Fluorometric Assay for the Measurement of Nitrite in Biological Samples. Anal.- Biochem. 1993, 214, 11-16.
16. Moehrle-Arcft. Pharm. Ber. Dtsch. Pharm. Ges. 1965,298,440-445.
17. Huber, L; FÜeloep, F.; Dombi, G.; Bernath, G.; Hermecz, I.; Meszaros, Z. A Facile Synthesis of 2-Imino-l-methylazacarbocycles. J. Chem. Soc., Perkin Trans, l 1987, 909-912.
18. Rao, K. R.; Nageswar, Y. V. D.; Srinivasan, T. N.; Sattur, P. B. Saturated Heterocycles. Part 88. Synthesis of a New Ring System: Dipyrido[l,2-a:4,3-d]pyrimidin-ll-one Derivatives. Synth. Commun. 1988,18 (8), 877-880.
19. Perrin, C. L.; Nunez. Absence of Stereoelectronic Control in Hydrolysis of Cyclic Amidines. J. Am. Chem. Soc. 1986, 108, 5997-6003.