Structure-activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 15, 2008, Pages 4388-4392

  Cuny, Gregory D ^a   Yu, Paul B ^b   Laha, Joydev K ^a   Xing, Xuechao ^a   Liu, Ji Feng ^c   Lai, Carol S ^b   Deng, Donna Y ^b   Sachidanandan, Chetana ^d   Bloch, Kenneth D ^b   Peterson, Randall T ^d  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b Anesthesia Center for Critical Care Research   (United States)

^c Aberjona Laboratories Inc   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN 2; BONE MORPHOGENETIC PROTEIN 6; BONE MORPHOGENETIC PROTEIN RECEPTOR 1; DORSOMORPHIN; LDN 193189; NITROGEN; OSTEOGENIN; PROTEIN INHIBITOR; PYRAZOLO[1,5 A]PYRIDINE; PYRIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; PYRROLO[1,2 A]PYRIMIDINE DERIVATIVE; QUINOLINE DERIVATIVE; SMAD1 PROTEIN; SMAD5 PROTEIN; SMAD8 PROTEIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG HALF LIFE; DRUG POTENCY; DRUG RESEARCH; FEMALE; LIVER MICROSOME METABOLISM; MALE; MOLECULAR PROBE; MOUSE; NONHUMAN; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS INHIBITION; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION;

ANIMALS; BONE MORPHOGENETIC PROTEIN RECEPTORS; BONE MORPHOGENETIC PROTEINS; COMBINATORIAL CHEMISTRY TECHNIQUES; FEMALE; MALE; MICE; MOLECULAR STRUCTURE; PIPERAZINES; PYRAZOLES; PYRIMIDINES; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP;

MUS;

EID: 47949090917     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.06.052     Document Type: Article

References (40)

1. Chen D., Zhao M., and Mundy G.R. Growth Factors 22 (2004) 233
2. Zwijsen A., Verschueren K., and Huylebroeck D. FEBS Lett. 546 (2003) 133
3. Nohe A., Keating E., Knaus P., and Petersen N.O. Cell Signal 16 (2004) 291
4. Eickelberg O., and Morty R.E. Trends Cardiovasc. Med. 17 (2007) 263
5. Yu P.B., Beppu H., Kawai N., Li E., and Bloch K.D. J Biol. Chem. 280 (2005) 24443
6. Liu D., Wang J., Kinzel B., Müeller M., Mao X., Valdez R., Liu Y., and Li E. Blood 110 (2007) 1502
7. Ye L., Lewis-Russell J.M., Kyanaston H.G., and Jiang W.G. Histol. Histopathol. 22 (2007) 1129
8. Kim I.Y., Lee D.H., Lee D.K., Kim B.C., Kim H.T., Leach F.S., Linehan W.M., Morton R.A., and Kim S.J. Clin. Cancer Res. 9 (2003) 6046
9. Billings P.C., Fiori J.L., Bentwood J.L., O'Connell M.P., Jiao X., Nussbaum B., Caron R.J., Shore E.M., and Kaplan F.S. J. Bone Miner Res. 23 (2008) 305
10. Shore E.M., Xu M., Feldman G.J., Fenstermacher D.A., Cho T.J., Choi I.H., Connor J.M., Delai P., Glaser D.L., LeMerrer M., Morhart R., Rogers J.G., Smith R., Triffitt J.T., Urtizberea J.A., Zasloff M., Brown M.A., and Kaplan F.S. Nat. Genet. 38 (2006) 525
11. Yu P.B., Hong C.C., Sachidanandan C., Babitt J.L., Deng D.Y., Hoyng S.A., Lin H.Y., Bloch K.D., and Peterson R.T. Nat. Chem. Biol. 4 (2008) 33
12. Babitt J.L., Huang F.W., Xia Y., Sidis Y., Andrews N.C., and Lin H.Y. J. Clin. Invest. 117 (2007) 1755
13. Weiss G., and Goodnough L.T. N. Engl. J. Med. 352 (2005) 1011
14. Gazzerro E., and Minetti C. Curr. Opin. Pharmacol. 7 (2007) 325
15. Whitty A., and Kumaravel G. Nat. Chem. Biol. 2 (2006) 112
16. Callahan J.F., Burgess J.L., Fornwald J.A., Gaster L.M., Harling J.D., Harrington F.P., Heer J., Kwon C., Lehr R., Mathur A., Olson B.A., Weinstock J., and Laping N.J. J. Med. Chem. 45 (2002) 999
17. Also know in the literature as "compound C".
18. This compound was initially reported as an AMP-activated protein kinase (AMPK) inhibitor, see:. Zhou G., Myers R., Li Y., Chen Y., Shen X., Fenyk-Melody J., Wu M., Ventre J., Doebber T., Fujii N., Musi N., Hirshman M.F., Goodyear L.J., and Moller D.E. J. Clin. Invest. 108 (2001) 1167
19. For similar compounds reported as KDR kinase inhibitors see:. Fraley M.E., Hoffman W.F., Rubino R.S., Hungate R.W., Tebben A.J., Rutledge R.Z., McFall R.C., Huckle W.R., Kendall R.L., Coll K.E., and Thomas K.A. Bioorg. Med. Chem. Lett. 12 (2002) 2767
20. Fraley M.E., Rubino R.S., Hoffman W.F., Hambaugh S.R., Arrington K.L., Hungate R.W., Bilodeau M.T., Tebben A.J., Rutledge R.Z., Kendall R.L., McFall R.C., Huckle W.R., Coll K.E., and Thomas K.A. Bioorg. Med. Chem. Lett. 12 (2002) 3537
21. Daniels R.N., Kim K., Lebois E.P., Muchalski H., Hughes M., and Lindsley C.W. Tetrahedron Lett. 49 (2008) 305
22. +, 407.1979).
23. 2, DCM, 0 °C to rt); (iii) conversion of the chloride to a nitrile (NaCN, DMF, rt).
24. For an alternate procedure see:. Engler T.A., Furness K., Malhotra S., Diefenbacher C., and Clayton J.R. Tetrahedron Lett. 44 (2003) 2903
25. Kitamura C., and Yamashita Y. J. Chem. Soc., Perkin Trans. 1 (1997) 1443
26. Marques M.A., Doss R.M., Urbach A.R., and Dervan P.B. Helv. Chim. Acta 85 (2002) 4485
27. Loeber S., Hueber H., Utz W., and Gmeiner P. J. Med. Chem. 44 (2001) 2691
28. Kondolff I., Doucet H., and Santelli M. Synlett (2005) 2057
29. Legault C., and Charette A.B. J. Org. Chem. 68 (2003) 7119
30. Tamaru Y., Sumida Y., Miki Y., and Ikeda M. J. Chem. Soc., Perkin Trans. 1 (1975) 406
31. Baudoin O. Angew. Chem., Int. Ed. 46 (2007) 1373
32. Forgione P., Brochu M.-C., St-Onge M., Thesen K.H., Bailey M.D., and Bilodeau F. J. Am. Chem. Soc. 128 (2006) 11350
33. Gooßen L.J., Deng G., and Levy L.M. Science 313 (2006) 662
34. Takata M., Filippov G., Liu H., Ichinose F., Janssens S., Bloch D.B., and Bloch K.D. Am. J. Physiol. Lung Cell Mol. Physiol. 280 (2001) L272
35. See Supplementary data for additional details.
36. Average values based on two to four independent experiments.
37. Sawyer J.S., Beight D.W., Britt K.S., Anderson B.D., Campbell R.M., Goodson Jr. T., Herron D.K., Li H.-Y., McMillen W.T., Mort N., Parsons S., Smith E.C.R., Wagner J.R., Yan L., Zhang F., and Yingling J.M. Bioorg. Med. Chem. Lett. 14 (2004) 3581
38. Gellibert F., Woolven J., Fouchet M.-H., Mathews N., Goodland H., Lovegrove V., Laroze A., Nguyen V.-L., Sautet S., Wang R., Janson C., Smith W., Krysa G., Boullay V., de Gouville A.-C., Huet S., and Hartley D. J. Med. Chem. 47 (2004) 4494
39. Wu Z., Fraley M.E., Bilodeau M.T., Kaufman M.L., Tasber E.S., Balitza A.E., Hartman G.D., Coll K.E., Rickert K., Shipman J., Shi B., Sepp-Lorenzino L., and Thomas K.A. Bioorg. Med. Chem. Lett. 14 (2004) 909
40. Baranczewski P., Stańczak A., Sundberg K., Svensson R., Wallin A., Jannson J., Garberg P., and Postlind H. Pharmacol. Rep. 58 (2006) 453