4-[5-Fluoro-3-[4-(2-methyl-1H-imidazol-1-yl)benzyloxy]phenyl]-3,4,5, 6-tetrahydro-2H-pyran-4-carboxamide, an Orally Active Inhibitor of 5-Lipoxygenase with Improved Pharmacokinetic and Toxicology Characteristics

Journal of Medicinal Chemistry

Volumn 47, Issue 3, 2004, Pages 720-725

  Mano, Takashi ^a   Okumura, Yoshiyuki ^a   Sakakibara, Minoru ^a   Okumura, Takako ^a   Tamura, Tetsuya ^a   Miyamoto, Kimitaka ^a   Stevens, Rodney W ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [5 FLUORO 3 [4 (2 METHYL 1H IMIDAZOL 1 YL)BENZYLOXY]PHENYL] 3,4,5,6 TETRAHYDRO 2H PYRAN 4 CARBOXAMIDE; IMIDAZOLE DERIVATIVE; LIPOXYGENASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CATARACTOGENESIS; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG METABOLISM; DRUG POTENCY; DRUG SYNTHESIS; LIPOPHILICITY; MALE; MONKEY; NONHUMAN; PH; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; ARACHIDONATE 5-LIPOXYGENASE; BIOLOGICAL AVAILABILITY; CATARACT; HAPLORHINI; HUMANS; IMIDAZOLES; MALE; MICE; PYRANS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 1642581053     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0303554     Document Type: Article

References (15)

1. Mano, T.; Stevens, R. W.; Ando, K.; Nakao, K.; Okumura, Y.; Sakakibara, M.; Okumura, T.; Tamura, T.; Miyamoto, K. Novel Imidazole Compounds as a New Series of Potent, Orally Active Inhibitors of 5-Lipoxygenase. Bioorg. Med. Chem. Lett. 2003, 11, 3879-3887.
2. (a) Aleo, M. D.; Drupa, C. A.; Fritz, C. A.; Walsh, C. M.; Whitman-Sherman, J. L.; Fortner, J. H. Alterations in lenticular sterol content precede CJ-12,918-induced cataract formation. Toxicol. Sci. 2001, 60 (Suppl.), 101.
3. (b) Baltrukonis, D. J.; Fritz, C. A.; Render, J. A.; Tengowski, M. W.; Costello, K.; Jakowski, A. B.; Fortner, J. H.; Lawton, M. P.; Nelms, L. F.; Drupa, C. A.; Verdugo-Gazdik, M. E.; Schnellmann, R. G.; Kajiji, S.; Aleo, M. D. Biochemical, molecular, and pathological mechanisms of CJ-12,918 cataract formation. Toxicol. Sci. 2001, 60 (Suppl.), 101.
4. (c) Aleo, M. D.; Avery, M. J.; Beierschmitt, W. P.; Drupa, C. A.; Fortner, J. H.; Kaplan, A. H.; Navetta, K. A.; Shepard, R. M.; Walsh, C. M. The use of explant lens culture to assess cataractogenic potential. In Toxicology for the Next Millennium; Isfort, R. J., Lederberg, J., Eds.; Annals of the New York Academy of Sciences, Vol. 919; New York Academy of Sciences: New York, 2000; pp 171-187.
5. Crawley, G. C.; Dowell, R. I.; Edwards, P. N.; Foster, S. J.; McMillan, R. M.; Walker, E. R. H.; Waterson, D.; Bird, T. G. C.; Bruneau, P.; Girodeau, J. M. Methoxytetrahydropyrans: a new series of selective and orally potent 5-lipoxygenase inhibitors. J. Med. Chem. 1992, 35, 2600-2609.
6. Foster, S. J.; Bruneau, P.; Walker, E. R. H.; McMillan, R. M. 2-Substituted indazolinones: orally active and selective 5-lipoxygenase inhibitors with anti-inflammatory activity. Br. J. Pharmacol. 1990, 99, 113-118.
7. (a) Young, J. M.; Maloney, P. J.; Jubb, S. N.; Clark, J. S. Pharmacological Investigation of the Mechanisms of Platelet-Activating Factor Induced Mortality in the Mouse. Prostaglandins 1985, 30, 545-551.
8. (b) Subissi, A.; Del Monte, M.; Criscuoli, M. Effects of anti-asthma drugs on PAF-induced death in mice. Prostaglandins 1988, 36, 797-806.
9. Manners, C. N.; Payling, D. W.; Smith, D. A. Lipophilicity of zwitterionic sulfate conjugates of tiaramide, propranolol, and 4′-hydroxypropranolol. Xenobiotica 1988, 18, 331-350.
10. ACD/LogP DB, version. 5.16; Advanced Chemistry Development Inc.: Toronto, Ontario, Canada, 2001.
11. Ple, P. A.; Bird, T. G. C. Oximes: a new class of methoxytetrahydropyranyl inhibitors of leukotriene biosynthesis with high in vitro and in vivo potency. Bioorg. Med. Chem. Lett. 1996, 6, 127-132.
12. Bird, T. G. C.; Olivier, A. Inhibitors of leukotriene B4. Synthesis and SAR of new-enaminoester open-chain analogues of Zeneca ZD2138. Bioorg. Med. Chem. Lett. 1996, 6, 515-520.
13. Dellaria, J. F., Jr.; Moore, J. L.; Hulkower, K. I.; Bouska, J. J.; Grayson, G. K.; Harris, R. R.; Bell, R. L.; Brooks, C. D. W.; Carter, G. W. Novel α-β-unsaturated ethers of 4-methoxy tetrahydropyran are orally active 5-lipoxygenase inhibitors. Book of Abstracts, 211th National Meeting of the American Chemical Society, New Orleans, LA, March 24-28, 1996; American Chemical Society, Washington, DC, 1996; MEDI 246.
14. Kamei, A.; Mizumoto, Y.; Takehana, M. The relationship between properties of antipsychotic drugs and cataract formation. Biol. Pharm. Bull. 1994, 17, 237-242.
15. Mano, T.; Stevens, R. W.; Ando, K.; Nakao, K.; Okumura, Y.; Sakakibara, M.; Okumura, T.; Tamura, T.; Miyamoto, K. Design and synthesis of a novel orally active 5-lipoxygenase inhibitor, CJ-13,610. Manuscript in preparation.