2-Benzimidazolyl-9-(chroman-4-yl)-purinone derivatives as JAK3 inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 23, 2009, Pages 6788-6792

  Cole, Andrew G ^a   Bohnstedt, Adolph C ^a   Paradkar, Vidyadhar ^a   Kingsbury, Celia ^a   Quintero, Jorge G ^a   Park, Haengsoon ^a   Lu, Yingchun ^a   You, Ming ^a   Neagu, Irina ^a   Diller, David J ^a   Letourneau, Jeffrey J ^a   Shao, Yuefei ^a   James, Ray A ^a   Riviello, Christopher M ^a   Ho, Koc Kan ^a   Lin, Tsung H ^a   Wang, Bojing ^a   Appell, Kenneth C ^a   Sills, Matthew ^a   Quadros, Elizabeth ^a   Kimble, Earl F ^a   Ohlmeyer, Michael H J ^a   Webb, Maria L ^a   more..

^a Ligand Pharmaceuticals Inc   (United States)

Author keywords

Benzimidazole; Chroman; JAK3; Janus kinase; Purinone; Rheumatoid arthritis

Indexed keywords

CHROMAN DERIVATIVE; FUNCTIONAL GROUP; GAMMA INTERFERON; INTERLEUKIN 2; JANUS KINASE 2; JANUS KINASE 3 INHIBITOR; PURINE DERIVATIVE;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; CYTOKINE PRODUCTION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG IDENTIFICATION; DRUG STRUCTURE; ENZYME ACTIVITY; FEMALE; MOUSE; NONHUMAN;

ANIMALS; BENZIMIDAZOLES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; ENZYME INHIBITORS; INTERFERON-GAMMA; INTERLEUKIN-2; JANUS KINASE 3; MICE; MODELS, ANIMAL; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PURINES; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 71749088434     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.09.080     Document Type: Article

References (16)

1. Wilkins A.F. Semin. Cell Dev. Biol. 19 (2009) 319
2. Macchi P., Villa A., Giliani S., Sacco M.G., Frattini A., Porta F., Ugazio A.G., Johnston J.A., Candotti F., O'Sheai J.J., Vezzoni P., and Notarangelo L.D. Nature 377 (1995) 65
3. Russell S.M., Tayebi N., Nakajima H., Riedy M.C., Roberts J.L., Aman M.J., Migone T., Noguchi M., Markert M.L., Buckley R.H., O'Shea J.J., and Leonard W.J. Science 270 (1995) 797
4. Pesu M., Laurence A., Kishore N., Zwillich S., Chan G., and O'Shea J.J. Immunol. Rev. 223 (2008) 132
5. Cetkovic-Cvrlje M., and Tibbles H.E. Curr. Pharm. Des. 10 (2004) 1767
6. Thompson J.E., Cubbon R.M., Cummings R.T., Wicker L.S., Frankshun R., Cunningham B.R., Cameron P.M., Meinke P.T., Liverton N.I., Weng Y., and DeMartino J.A. Bioorg. Med. Chem. Lett. 12 (2002) 1219
7. Adams C., Aldous D.J., Amendola S., Bamborough P., Bright C., Crowe S., Eastwood P., Fenton G., Foster M., Harrison T.K.P., King S., Lai J., Lawrence C., Letallec J.-P., McCarthy C., Moorcroft N., Page K., Rao S., Redford J., Sadiq S., Smith K., Souness J.E., Thurairatnam S., Vine M., and Wyman B. Bioorg. Med. Chem. Lett. 13 (2003) 3105
8. Chen J.J., Thakur K.D., Clark M.P., Laughlin S.K., George K.M., Bookland R.G., Davis J.R., Cabrera E.J., Easwaran V., De B., and Zhang G. Bioorg. Med. Chem. Lett. 16 (2006) 5633
9. Changelian P.S., Flanagan M.E., Ball D.J., Kent C.R., Magnuson K.S., Martin W.H., Rizzuti B.J., Sawyer P.S., Perry B.D., Brissette W.H., McCurdy S.P., Kudlacz E.M., Conklyn M.J., Elliott E.A., Koslov E.R., Fisher M.B., Strelevitz T.J., Yoon K., Whipple D.A., Sun J., Munchhof M.J., Doty J.L., Casavant J.M., Blumenkopf T.A., Hines M., Brown M.F., Lillie B.M., Subramanyam C., Shang-Poa C., Milici A.J., Beckius G.E., Moyer J.D., Su C., Woodworth T.G., Gaweco A.S., Beals C.R., Littman B.H., Fisher D.A., Smith J.F., Zagouras P., Magna H.A., Saltarelli M.J., Johnson K.S., Nelms L.F., Des Etages S.G., Hayes L.S., Kawabata T.T., Finco-Kent D., Baker D.L., Larson M., Si M., Paniagua R., Higgins J., Bruce Reitz H.B., Zhou Y., Morris R.E., O'Shea J.J., and Borie D.C. Science 302 (2003) 875
10. Boy, M. G.; Wang, C.; Wilkinson, B. E.; Chow, V. F.; Clucas, A. T.; Krueger, J. G.; Gaweco, A. S.; Zwillich, S. H.; Changelian, P. S.; Chan, G. J. Invest. Dermatol. 2009, 129, 2299.
11. Avan Gurp E., Weimar W., Gaston R., Brennan D., Mendez R., Pirsch J., Swan S., Pescovitz M.D., Ni G., Wang C., Krishnaswami S., Chow V., and Chan G. Am. J. Transplant. 8 (2008) 1711
12. Recombinant human JAK3 (508aa to 1124aa) and JAK2 (532aa to 1132aa) were generated using a baculovirus expression system. Test compounds were incubated with JAK3 or JAK2, the peptide substrate biotinylated poly Glu-Ala-Tyr, and ATP for 60 min at room temperature. The tyrosine phosphorylation of biotinylated substrate was detected using Europium (LANCE) labeled anti-phosphotyrosine antibody and DyLight conjugated streptavidin, and the time-resolved fluorescence signals were measured using a plate reader.
13. Cole A.G., Metzger A., Ahmed G., Brescia M.-R., Chan R.J., Wen J., O'Brien L., Qin L.-Y., and Henderson I. Tetrahedron Lett. 47 (2006) 8897
14. Cole A.G., Stroke I.L., Brescia M.-R., Simhadri S., Zhang J.J., Hussain Z., Snider M., Haskell C., Ribeiro S., Appell K.C., Henderson I., and Webb M.L. Bioorg. Med. Chem. Lett. 16 (2006) 200
15. Shao Y., Cole A.G., Brescia M.-R., Qin L.-Y., Duo J., Stauffer T.M., Rokosz L.L., McGuinness B.F., and Henderson I. Bioorg. Med. Chem. Lett. 19 (2009) 1399
16. Skupinska K.A., McEachern E.J., Baird I.R., Skerlj R.T., and Bridger G.J. J. Org. Chem. 68 (2003) 3546