Design and synthesis of orally active inhibitors of TNF synthesis as anti-rheumatoid arthritis drugs

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 22, 2003, Pages 3951-3954

  Chen, Jian Jeffrey ^a,b   Dewdney, Nolan ^a   Lin, Xiaohong ^a   Martin, Robert L ^a   Walker, Keith A M ^a   Huang, Jane ^a   Chu, Frances ^a   Eugui, Elsie ^a   Mirkovich, Anna ^a   Kim, Yong ^a   Sarma, Keshab ^a   Arzeno, Humberto ^a   Van Wart, Harold E ^a  

^a ROCHE BIOSCIENCE   (United States)

^b AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFLAMMATORY AGENT; ANTIRHEUMATIC AGENT; MATRIX METALLOPROTEINASE INHIBITOR; PROTEIN INHIBITOR; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; DRUG IDENTIFICATION; DRUG SYNTHESIS; EXPERIMENTAL MODEL; MALE; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALIA;

EID: 10744227527     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2003.08.076     Document Type: Article

References (16)

1. For a general review on RA, see: Smolen J.S., Seiner G. Nat. Rev. Drug Discov. 2:2003;473.
2. For a general review see: Newton R.C., Decicco C.P. J. Med. Chem. 42:1999;2295.
3. For the latest review on MMP, see: Clark I.M., Parker A.E. Exp. Opin. Ther. Targets. 7:2003;19.
4. For the latest review on anti-TNF biologics, see: Machold K.P., Smolen J.S. Exp. Opin. Biol. Ther. 3:2003;351.
5. Day R. Lancet. 359:2002;540.
6. Nelson F.C., Zask A. Exp. Opin. Invest. Drugs. 8:1999;383.
7. Moss M.L., White J.M., Lambert M.H., Andrew R.C. Drug Discov. Today. 6:2001;417.
8. Stocker W., Grams F., Baumann U., Reinemer P., Gomis-Ruth F.-X., Mckay D.B., Bode W. Protein Sci. 4:1995;823.
9. Hooper N.M. FEBS Lett. 354:1994;1.
10. Gearing A., Beckett M., Christodoulou M., Churchill M., Clements J., Davidson A., Drummond A., Galloway W., Gilbert R., Gordon J., Leber T., Mangan M., Miller K., Nayee P., Owens K., Patel S., Thomas W., Wells G., Wood L., Wooley K. Nature. 370:1994;555.
11. McGeehan G., Becherer J., Bast R., Boyer C., Champion B., Connolly K., Conway J., Furdon P., Karp S., Kidao S., McElroy A., Nichols J., Pryzwansky K., Schoenen F., Sekut L., Truesdale A., Verghese M., Warner J., Ways J. Nature. 370:1994;558.
12. (a) Only a few latest references are given: Duan J.J.-W., Lu Z., Xue C., He X., Seng J.L., Roderick J.J., Wasserman Z.R., Liu R., Covington M.B., Magolda R.L., Newton R.C., Trzaskos J.M., Decicco C.P. Bioorg. Med. Chem. Lett. 13:2003;2035 (b) Zask A., Gu Y., Albright J.D., Du X., Hogan M., Levin J.I., Chen J.M., Killar L.M., Sung A., DiJoseph J.F., Sharr M.A., Roth C.E., Skala S., Jin G., Cowling R., Mohler K.M., Barone D., Black R., March C., Skotnicki J.S. Bioorg. Med. Chem. Lett. 13:2003;1487 (c) Sawa M., Kurokawa K., Inoue Y., Kondo H., Yoshino K. Bioorg. Med. Chem. Lett. 13:2003;2021.
13. (b) Zask A., Gu Y., Albright J.D., Du X., Hogan M., Levin J.I., Chen J.M., Killar L.M., Sung A., DiJoseph J.F., Sharr M.A., Roth C.E., Skala S., Jin G., Cowling R., Mohler K.M., Barone D., Black R., March C., Skotnicki J.S. Bioorg. Med. Chem. Lett. 13:2003;1487
14. (a) . Only a few latest references are given: Duan J.J.-W., Lu Z., Xue C., He X., Seng J.L., Roderick J.J., Wasserman Z.R., Liu R., Covington M.B., Magolda R.L., Newton R.C., Trzaskos J.M., Decicco C.P. Bioorg. Med. Chem. Lett. 13:2003;2035 (b) Zask A., Gu Y., Albright J.D., Du X., Hogan M., Levin J.I., Chen J.M., Killar L.M., Sung A., DiJoseph J.F., Sharr M.A., Roth C.E., Skala S., Jin G., Cowling R., Mohler K.M., Barone D., Black R., March C., Skotnicki J.S. Bioorg. Med. Chem. Lett. 13:2003;1487 (c) Sawa M., Kurokawa K., Inoue Y., Kondo H., Yoshino K. Bioorg. Med. Chem. Lett. 13:2003;2021.
15. Broka, C. A.; Campbell, J. A.; Castelhano, A. L.; Chen, J. J.; Hendricks, R. T.; Melnick, M. J.; Walker, A. M. US Patent 6143744, 2000; Chem. Abstr. 2002, 136, 340996.
16. Induction and assessment of collagen-induced arthritis: male DBA/1J (6-8 weeks old) mice were immunized intradermally in the base of the tail with 0.1 mL of an emulsion of 100 μg of bovine type II collagen (Chondrex, Seattle, WA, USA) in Freund's complete adjuvant on day 0. Four weeks after the immunization, when some animals began to show signs of inflammation, mice were challenged with an intraperitoneal injection of 0.5 mL (50 μg) of lip polysaccharide (LPS, E. coli, Sigma, Cat.# L3129). Mice were dosed orally once a day with either vehicle or compound 17 at the doses indicated in Table 3, beginning 24 h after the LPS boost and lasting 14 days. The extremities were evaluated three times each week and the severity of the arthritis on each paw was scored on a scale of 0-4. The score 0 represented a normal paw and a score of 4 represented severe arthritis on the digits and paws with the mouse avoiding weight-bearing on the paw. Groups of 10-12 mice were used for each dose group and for the vehicle controls.