Synthesis and structure-activity relationship of benzetimide derivatives as human CXCR3 antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 21, 2008, Pages 5819-5823

  Bongartz, Jean Pierre ^a   Buntinx, Mieke ^a   Coesemans, Erwin ^a   Hermans, Bart ^a   Lommen, Guy Van ^b   Wauwe, Jean Van ^a  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^b GALAPAGOS NV   (Belgium)

Author keywords

Benzetimide; Chemokine; CXCR3 antagonist

Indexed keywords

AMG 487; BENZETIMIDE; CHEMOKINE RECEPTOR ANTAGONIST; CHEMOKINE RECEPTOR CXCR3; CHEMOKINE RECEPTOR CXCR3 ANTAGONIST; CXCL11 CHEMOKINE; CXCL9 CHEMOKINE; GAMMA INTERFERON INDUCIBLE PROTEIN 10; METHYLSCOPOLAMINE; MUSCARINIC M1 RECEPTOR; MUSCARINIC M2 RECEPTOR; MUSCARINIC M3 RECEPTOR; MUSCARINIC RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG;

ANIMAL CELL; ANTICHOLINERGIC EFFECT; ARTICLE; CELL MIGRATION; CHIRALITY; CHO CELL; CONTROLLED STUDY; DEBENZYLATION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; HELPER CELL; HUMAN; HUMAN CELL; IC 50; MICHAEL ADDITION; NONHUMAN; PHARMACOPHORE; STRUCTURE ACTIVITY RELATION;

DEXETIMIDE; HUMANS; RECEPTORS, CXCR3; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 54049130740     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.07.115     Document Type: Article

References (32)

1. Murphy P.M., Baggiolini M., Charo I.F., Horuk R., Matsushima K., Miller L.H., Oppenheimer J.J., and Power C.A. Pharmacol. Rev. 52 (2000) 145
2. Loetscher M., Loetscher P., Brass N., Meese E., and Moser B. Eur. J. Immunol. 28 (1998) 3696
3. Medina J., Johnson M.G., and Collins T.L. Ann. Rep. Med. Chem. 40 (2005) 215
4. Tensen C.P., Flier J., Van Der Raaij-Helmer E.M., Sampat-Sardjoepersad S., Van Der Schors R.C., Leurs R., Scheper R.J., Boorsma D.M., and Willemze R.J. J. Invest. Dermatol. 112 (1999) 716
5. Lazzeri E., and Romagnani P. Curr. Drug Targets 5 (2005) 109
6. Hancock W., Lu B., Gao W., Csizmadia V., Faia K., King J.A., Smiley S.T., Ling M., Gerard N.P., and Gerard C. J. Exp. Med. 192 (2000) 1515
7. Belperio J.A., Keane M.P., Burdick M.D., Lynch III J.P., Zisman D.A., Xue Y.Y., Li K., Ardehali A., Ross D.J., and Strieter R.M. J. Immunol. 171 (2003) 4844
8. Sørensen T.L., Trebst C., Kivisäll P., Klaege K.L., Majmudar A., Ravid R., and Lassmann H. J. Neuroimmunol. 127 (2002) 59
9. Sindern E., Patzhold T., Ossege L.M., Gisevius A., and Malin J.-P. J. Neuroimmunol. 131 (2002) 186
10. Olsen D.B., Strieter R.M., Ransohoff R.M., and Sellebjerg F. J. Neuroimmunol. 127 (2002) 59
11. Sasaki S., Yoneyama H., Suzuki K., Suriki H., Aiba T., Watanabe S., Kawachi H., Shimizu F., Matsuashima K., Asakurri H., and Narumi S. Eur. J. Immunol. 32 (2002) 3197
12. Frigerio S., Junt T., Lu B., Gerard C., Zumsted U., Holländer G.A., and Piali L. Nat. Med. 8 (2002) 1414
13. Saetta M., Mariani M., Panina-Bordignon P., Turato G., Buonsanti C., Baraldo S., Bellettato C.M., Papi A., Corbetta L., Zuin R., Sinigaglia F., and Fabbri L.M. Am. J. Respir. Crit. Care 165 (2002) 1404
14. Flier J., Boorsma D.M., Bruynzeel D.P., van Beek P., Stoof T.J., Scheper R.J., Willemze R., and Tensen C.P. J. Invest. Dematol. 113 (1999) 574
15. Qin S., Rottman J.B., Myers P., Kassam N., Wienblatt M., Loetscher M., Koch A.E., Moser B., and Mackay C.R. J. Clin. Invest. 101 (1998) 746
16. Storelli S., Verdijk P., Verzijl D., Timmerman H., van de Stolpe A., Tensen C.P., Smit M.J., De Esch I.J.P., and Leurs R. Bioorg. Med. Chem. Lett. 15 (2005) 2910
17. Allen D.R., Bolt A., Chapman G.A., Knight R.L., Meissner J.W.G., Owen D.A., and Watson R.J. Bioorg. Med. Chem. Lett. 17 (2007) 697
18. Johnson M., Li A.-R., Liu J., Fu Z., Zhu L., Miao S., Wang X., Xu Q., Huang A., Marcus A., Xu F., Ebsworth K., Sablan E., Danao J., Kumer J., Dairaghi D., Lawrence C., Sullivan T., Tonn G., Schall T., Collins T., and Medina J. Bioorg. Med. Chem. Lett. 17 (2007) 3339
19. Watson R.J., Allen D.R., Birch H.L., Chapman G.A., Galvin F.C., Jopling L.A., Knight R.L., Meier D., Oliver K., Meissner J.W.G., Owen D.A., Thomas E.J., Tremayne N., and Williams S.C. Bioorg. Med. Chem. Lett. 18 (2008) 147
20. Du X., Chen X., Mihalic J.T., Deignan J., Duquette J., Li A.-R., Lemon B., Ma J., Miao S., Ebsworth K., Sullivan T.J., Tonn G., Collins T.L., and Medina J.C. Bioorg. Med. Chem. Lett. 18 (2008) 608
21. Li A.R., Johnson M.G., Liu J., Chen X., Du X., Mihalic J.T., Deignan J., Gustin D.J., Duquette J., Fu Z., Zhu L., Marcus A.P., Bergeron P., McGee L.R., Danao J., Lemon B., Carabeo T., Sullivan T., Ma J., Tang L., Tonn G., Collins T.L., and Medina J.C. Bioorg. Med. Chem. Lett. 18 (2008) 688
22. 6 cells/well in DMEM/HAM'S F12 medium supplemented with 10% fetal bovine serum and 1 mM isobutylmethylxanthine. After a 60-min pre-incubation at room temperature with compound, forskolin (30 μM) and ITAC (0.3 μM, Peprotech) were added. After 30 min, intracellular cAMP was measured using the cAMP dynamic kit from CIS bio International.
23. 35 S]GTPγS (0.25 nM, ∼1119 Ci/mmol, Amersham) was then added and, 30 min later, bound radioactivity was determined on a Topcount (Packard).
24. Johnson, M.G.; Li, A.; Liu, J.; Marcus, A.P.; Huang, A.X.; Medina, J.C. Abstracts of Papers; 231st National Meeting of the American Chemical Society: Atlanta, Ga, 2006.
25. Johnson M., Li A.R., Liu J., Fu Z., Zhu L., Miao S., Wang X., Xu Q., Huang A., Marcus A., Xu F., Ebsworth K., Sablan E., Danao J., Kumer J., Dairaghi D., Lawrence C., Sullivan T., Tonn G., Schall T., Collins T., and Medina J. Bioorg. Med. Chem. Lett. 17 (2007) 3339
26. Muscarinic receptor binding data were obtained from MDS Pharma Services, Bothell, WA 98021, USA.
27. Janssen P.A.J., Niemegeers C.J.E., Schellekens K.H.L., Demoen P., Lenaerts F.M., Van Nueten J.M., Van Wijngaarden I., and Brugmans. J. Drug Res. 21 (1971) 1365
28. Human peripheral blood mononuclear cells (PBMCs) were activated with PHA and human IL-2 (R&D Systems) for 3 days and further cultured with IL-2 until the day of analysis (days 9-14). Cells were labeled with Calcein-AM (Invitrogen) and dissolved in HBSS supplemented with 0.2% BSA. After pre-incubation with compound (10 min, 25 °C), 20 μl cell suspension (80,000 cells) was added in 6-fold to the topside of the filter, while the bottom wells of the 96-well chemotaxis chambers (ChemoTx, NeuroProbe) were filled with 3 nM human ITAC. After 3 h at 37 °C, non-migrated cells were removed from the filter and migrated cells were measured using a fluorescent plate reader.
29. 125I]-ITAC (2000 Ci/mmol, Amersham) was added and kept for 60 min at 4 °C. Cells were harvested upon GF/B filter plates (presoaked in 0.5% polyethyleneimine) and radioactivity was determined by liquid scintillation counting.
30. Chemokine receptor binding data were obtained from MDS Pharma Services, Bothell, WA 98021, USA.
31. Coesemans, E.; Bongartz, J.-P. A. M.; Van Lommen, G. R. E.; Van Wauwe, J. P. F.; Buntinx, M. WO Patent 090826, 2007.
32. Coesemans, E.; Bongartz, J.-P. A. M.; Van Lommen, G. R. E. WO Patent 090836, 2007.