C(4)-alkyl substituted furanyl cyclobutenediones as potent, orally bioavailable CXCR2 and CXCR1 receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 13, 2007, Pages 3778-3783

  Chao, Jianhua ^a   Taveras, Arthur G ^a   Chao, Jianping ^a   Aki, Cynthia ^a   Dwyer, Michael ^a   Yu, Younong ^a   Purakkattle, Biju ^a   Rindgen, Diane ^a   Jakway, James ^a   Hipkin, William ^a   Fosetta, James ^a   Fan, Xuedong ^a   Lundell, Daniel ^a   Fine, Jay ^a   Minnicozzi, Michael ^a   Phillips, Jonathan ^a   Merritt, J Robert ^b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b PHARMACOPEIA INC   (United States)

Author keywords

CXCR1 receptor; CXCR2 receptor; Dual antagonists

Indexed keywords

CHEMOKINE RECEPTOR ANTAGONIST; CHEMOKINE RECEPTOR CXCR1; CHEMOKINE RECEPTOR CXCR2; CYCLOBUTANE DERIVATIVE; INTERLEUKIN 8; MELANOMA GROWTH STIMULATORY ACTIVITY FACTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOAVAILABILITY; DRUG MECHANISM; HUMAN; HUMAN CELL; INFLAMMATION; INHIBITION KINETICS; MOUSE; NEUTROPHIL; NEUTROPHIL CHEMOTAXIS; NONHUMAN; RAT;

ADMINISTRATION, ORAL; ANIMALS; AREA UNDER CURVE; CHEMISTRY, PHARMACEUTICAL; DOGS; DRUG DESIGN; FURANS; HUMANS; INHIBITORY CONCENTRATION 50; INTERLEUKIN-8; KINETICS; MICE; RATS; RECEPTORS, INTERLEUKIN-8A; RECEPTORS, INTERLEUKIN-8B;

CANIS FAMILIARIS; RATTUS;

EID: 34250197581     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.04.016     Document Type: Article

References (36)

1. Murphy P.M., Baggiolini M., Charo I.F., Hebert C.A., Horuk R., and Matsushima K. Pharmacol. Rev. 52 (2000) 145
2. Holmes W.E., Lee J., Kuang W.J., Rice G.C., and Wood W.I. Science 253 (1991) 1278
3. Murphy P.M., and Tiffany H.L. Science 253 (1991) 1280
4. Miller E.J., Cohen A.B., Nagao S., Griffith D., Maunder R.J., Martin T.R., Weiner-Kronish J.P., Sticherling M., Christophers E., and Matthay M.A. Am. Rev. Respir. Dis. 146 (1992) 427
5. Strieter R.M., Keane M.P., Burdick M.D., Sakkour A., Murray L.A., and Belperio J.A. Curr. Drug Targets Inflamm. Allergy 4 (2005) 299
6. Barnes P.J. Pulmon. Pharm. Ther. 12 (1999) 67
7. Keatings V.M., Collins P.D., Scott D.M., and Barnes P.J. Am. J. Respir. Crit. Care Med. 153 (1996) 530
8. Kulke R., Bornscheuer E., Schluter C., Bartels J., Rowert J., Sticherling M., and Christophers E. J. Invest. Dermatol. 110 (1998) 90
9. Homey B. Curr. Drug Targets Inflamm. Allergy 3 (2004) 169
10. Williams E.J., Haque S., Banks C., Johnson P., Sarsfield P., and Sheron N. J. Pathol. 192 (2000) 533
11. Small molecule CXCR2 or CXCR1 antagonists:. Dwyer M.P., Yu Y., Chao J., Aki C., Chao J., Purakkattle B., Girijavallabhan V., Rindgen D., Bond R., Mayer-Ezel R., Jakway J., Hipkin R.W., Fosetta J., Gonsiorek W., Bian H., Fan X., Terminelli C., Fine J., Lundell D., Merritt J.R., Rokosz L.L., Kaiser B., Li G., Wang W., Stauffer T., Ozgur L., Baldwin J., and Taveras A.G. J. Med. Chem. 49 (2006) 7603
12. Nie H., Widdowson K.L., Palovich M.R., Fu W., Elliott J.D., Bryan D.L., Burman M., Schmidt D.B., Foley J.F., Sarau H.M., and Busch-Petersen J. Bioorg. Med. Chem. Lett. 16 (2006) 5513
13. Merritt J.R., Rokosz L.L., Nelson Jr. K.H., Kaiser B., Wang W., Stauffer T.M., Ozgur L.E., Schilling A., Li G., Baldwin J.J., Taveras A.G., Dwyer M.P., and Chao J. Bioorg. Med. Chem. Lett. 16 (2006) 4107
14. Ho K.-K., Auld D.S., Bohnstedt A.C., Conti P., Dokter W., Erickson S., Feng D., Inglese J., Kingsbury C., Kultgen S.G., Liu R.-Q., Masterson C.M., Ohlmeyer M., Rong Y., Rooseboom M., Roughton A., Samama P., Smit M.-J., Son E., van der Louw J., Vogel G., Webb M., Wijkmans J., and You M. Bioorg. Med. Chem. Lett. 16 (2006) 2724
15. Allegretti M., Bertini R., Cesta M.C., Bizzarri C., Bitondo R.D., Cioccio V.D., Galliera E., Berdini V., Topai A., Zampella G., Russo V., Bello N.D., Nano G., Nicolini L., Locati M., Fantucci P., Florio S., and Colotta F. J. Med. Chem. 48 (2005) 4312
16. Widdowson K.L., Elliott J.D., Veber D.F., Nie H., Rutledge M.C., McCleland B.W., Xiang J.-N., Jurewicz A.J., Hertzberg R.P., Foley J.J., Griswold D.E., Martin L., Lee J.M., White J.R., and Sarau H.M. J. Med. Chem. 47 (2004) 1319
17. Jin Q., Nie H., McCleland B.W., Widdowson K.L., Palovich M.R., Elliott J.D., Goodman R.M., Burman M., Sarau H.M., Ward K.W., Nord M., Orr B.M., Gorycki P.D., and Busch-Petersen J. Bioorg. Med. Chem. Lett. 14 (2004) 4375
18. Weidner-Wells M.A., Henninger T.C., Fraga-Spano S.A., Boggs C.M., Matheis M., Ritchie D.M., Argentieri D.C., Wachter M.P., and Hlasta D.J. Bioorg. Med. Chem. Lett. 14 (2004) 4307
19. Baxter A., Bennion C., Bent J., Boden K., Brough S., Cooper A., Kinchin E., Kindon N., McInally T., Mortimore M., Roberts B., and Unitt J. Bioorg. Med. Chem. Lett. 13 (2003) 2625
20. Li J.J., Carson K.G., Trivedi B.K., Yue W.S., Ye Q., Glynn R.A., Miller S.R., Connor D.T., Roth B.D., Luly J.R., Low J.E., Heilig D.J., Yang W., Qin S., and Hunt S. Bioorg. Med. Chem. 11 (2003) 3777
21. Mahler D.A., Huang S., Tabrizi M., and Bell G.M. Chest 126 (2004) 926
22. http://www.anogen.ca/antibodies_abcream.htm.
23. Bizzarri C., Beccari A.R., Bertini R., Cavicchia M.R., Giorgini S., and Allegretti M. Pharmacol. Ther. 112 (2006) 139
24. Busch-Petersen, J.; Jin, Q.; McCleland, B. W.; Nie, H.; Palovich, M. R.; Davis, R. S.; Fu, W.; Elliott, J. D.; Burman, M.; Foley, J. J.; Schmidt, D. B.; Podolin, P.; Bolognese, B. J.; Underwood, D. C.; Osborn, R. R.; Dehaas, C. J.; Salmon, M.; Carpenter, D. C.; Killian, D. J.; Sarau, H. M.; Widdowson, K. L. In Abstracts of Papers, 228th National Meeting of the American Chemical Society, Philadelphia, PA, United States, August 22-26, 2004; American Chemical Society: Washington, DC, 2004; MEDI-192.
25. Dwyer, M. P.; Yu, Y.; Chao, J.; Aki, C.; Chao, J.; Purakkattle, B.; Rindgen, D.; Bond, R.; Jakway, J.; Hipkin, R. W.; Fosetta, J.; Gonsiorek,W.; Bian, H.; Fine, J.; Merritt, J. R.; Rokosz, L. L.; Kaiser, B.; Li, G.; Wang, W.; Stauffer, T.; Ozgur, L.; Taveras, A. In Abstract of Papers, 231st National Meeting of the American Chemical Society, Atlanta, GA, United States, March 26-30, 2006; American Chemical Society: Washington, DC, 2006; MEDI-019.
26. 50 by correcting for the radioligand concentration used in the binding assay.
27. 50 of 16 is 3.7 nM.
28. for assay conditions, refer to:. Spond J., Billah M.M., Chapman R.W., Egan R.W., Hey J.A., House A., Kreutner W., and Minnicozzi M. Pulmon. Pharm. Ther. 17 (2004) 133
29. for assay conditions, refer to:. Thatcher T.H., McHugh N.A., Egan R.W., Chapman R.W., Hey J.A., Turner C.K., Redonnet M.R., Seweryniak K.E., Sime P.J., and Phipps R.P. Am. J. Physiol. Lung Cell Mol. Physiol. 289 (2005) L322
30. Wiley R.A., Choo H.-Y., and McClellan D. J. Org. Chem. 48 (1983) 1106
31. Gilman H., and Turck Jr. J.A.V. J. Am. Chem. Soc. 61 (1939) 473
32. Ono N., Jun T.X., and Kaji A. Synthesis (1987) 821
33. Alvaro G., Martelli G., Savoia D., and Zoffoli A. Synthesis (1998) 1773
34. In most cases, the addition of organolithium reagents to imine 53 produced one diastereomer detectable by Hnmr.
35. Soloshonok V., and Ono T. J. Org. Chem. 62 (1997) 3030
36. Chiral amine salt 63 was derivatized with (R)-(-)-Mosher's acid chloride, and the de of the diastereomeric amides was determined to be 83% based on Hnmr analysis of the crude product mixture.