Design, synthesis, and evaluation of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 3, 2010, Pages 922-926

  Kim, Ikyon ^a   Song, Jong Hwan ^a   Park, Chang Min ^a   Jeong, Joon Won ^a   Kim, Hyung Rae ^a   Ha, Jin Ryul ^a   No, Zaesung ^b   Hyun, Young Lan ^c   Cho, Young Sik ^a   Sook Kang, Nam ^a   Jeon, Dong Ju ^a  

^a Korea Research Institute of Chemical Technology   (South Korea)

^b Institute Pasteur Korea   (South Korea)

^c CrystalGenomics Inc   (South Korea)

Author keywords

Asthma; COPD; PDE 4 inhibitor; SBDD

Indexed keywords

2 ARYL 7 (3',4' DIALKOXYPHENYL) PYRAZOLO[1,5-ALPHA]PYRIMIDINE; CILOMILAST; L 826 141; PHOSPHODIESTERASE IV; PHOSPHODIESTERASE IV INHIBITOR; ROFLUMILAST; ROLIPRAM; UNCLASSIFIED DRUG; PHOSPHODIESTERASE INHIBITOR; PYRAZOLE DERIVATIVE; PYRIMIDINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ASTHMA; CONTROLLED STUDY; CRYSTAL STRUCTURE; DISEASE MODEL; DRUG BINDING SITE; DRUG DESIGN; DRUG DETERMINATION; DRUG EFFECT; DRUG POTENCY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION; TREATMENT OUTCOME; TREATMENT RESPONSE; X RAY CRYSTALLOGRAPHY; ANIMAL; COMPARATIVE STUDY; METABOLISM; PROCEDURES; SYNTHESIS;

ANIMALS; CRYSTALLOGRAPHY, X-RAY; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 4; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; HUMANS; MICE; PHOSPHODIESTERASE 4 INHIBITORS; PHOSPHODIESTERASE INHIBITORS; PYRAZOLES; PYRIMIDINES;

EID: 74349090277     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.12.070     Document Type: Article

References (38)

1. Beavo J.A., and Reifsnyder D.H. Trends Pharmacol. Sci. 11 (1990) 150
2. Verghese M.W., and Snyderman R. In: Zembala M., and Asherson G.L. (Eds). Human Monocytes (1989), Academic, London 101
3. Giembycz M.A., and Dent G. Clin. Exp. Allergy 22 (1992) 337
4. Torphy T.J., Livi G.P., and Christensen S.B. Drug News Perspect. 6 (1993) 203
5. Christensen S.B., and Torphy T.J. Annu. Rep. Med. Chem 29 (1994) 185
6. Schwabe U., Miyake M., Ohga Y., and Daly J. Mol. Pharmacol. 12 (1976) 900
7. Zeller E., Stief H.J., Pflug B., Sastre Y., and Hernandez M. Pharmacopsychiatry 59 (1988) 358
8. Masamune H., Cheng J.B., Cooper K., Eggler J.F., Marfat A., Marshall S.C., Shirley J.T., Tickner J.E., Umland J.P., and Vazquez E. Bioorg. Med. Chem. Lett. 5 (1995) 1965
9. Cheng J.B., Cooper K., Duplantier A.J., Eggler J.F., Kraus K.G., Marshall S.C., Marfat A., Masamune H., Shirley J.T., Tickner J.E., and Umland J.P. Bioorg. Med. Chem. Lett. 5 (1995) 1969
10. Duplantier A.J., Biggers M.S., Chambers R.J., Cheng J.B., Cooper K., Damon D.B., Eggler J.F., Kraus K.G., Marfat A., Masamune H., Pillar J.S., Shirley J.T., Umland J.P., and Watson J.W. J. Med. Chem. 39 (1996) 120
11. Chambers R.J., Marfat A., Cheng J.B., Cohan V.L., Damon D.B., Duplantier A.J., Hibbs T.A., Jenkinson T.H., Johnson K.L., Kraus K.G., Pettipher E.R., Salter E.D., Shirley J.T., and Umland J.P. Bioorg. Med. Chem. Lett. 7 (1997) 739
12. Piaz V.D., Giovannoni M.P., Castellana C., Palacios J.M., Beleta J., Doménech T., and Segarra V. J. Med. Chem. 40 (1997) 1417
13. Hulme C., Poli G.B., Huang F.-C., Souness J.E., and Djuric S.W. Bioorg. Med. Chem. Lett. 8 (1998) 175
14. Friesen R.W., Ducharme Y., Ball R.G., Blouin M., Boulet L., Côté B., Frenette R., Girard M., Guay D., Huang Z., Jones T.R., Laliberté F., Lynch J.J., Mancini J., Martins E., Masson P., Muise E., Pon D.J., Siegel P.K.S., Styhler A., Tsou N.N., Turner M.J., Young R.N., and Girard Y. J. Med. Chem. 46 (2003) 2413
15. Huai Q., Wang H., Sun Y., Kim H.Y., Liu Y., and Ke H. Structure 11 (2003) 865
16. Card G.L., England B.P., Suzuki Y., Fong D., Powell B., Lee B., Luu C., Tabrizizad M., Gillette S., Ibrahim P.N., Artis D.R., Bollag G., Milburn M.V., Kim S.H., Schlessinger J., and Zhang K.Y. Structure 12 (2004) 2233
17. For selected synthesis and biological evaluation of pyrazolopyrimidines, see:. Hammouda H.A., El-Barbary A.A., and Sharaf M.A.F. J. Heterocycl. Chem. 21 (1984) 945
18. Bruni F., Selleri S., Costanzo A., Guerrini G., Casilli M.L., and Giusti L. J. Heterocycl. Chem. 32 (1995) 291
19. Almansa C., de Arriba A.F., Cavalcanti F.L., Gomez L.A., Miralles A., Merlos M., Garcia-Rafanell J., and Forn J. J. Med. Chem. 44 (2001) 350
20. Elmaati T.M.A., Said S.B., Elenein N.S.A., Khodeir N.M., and Sofan M.M. J. Heterocycl. Chem. 40 (2003) 481
21. Danagulyan G.G., Mkrtchyan A.D., and Panosyan G.A. Chem. Heterocycl. Compd. 41 (2005) 485
22. Selleri S., Gratteri P., Costagli C., Bonaccini C., Costanzo A., Melani F., Guerrini G., Ciciani G., Costa B., Spinetti F., Martini C., and Bruni F. Bioorg. Med. Chem. 13 (2005) 4821
23. Zhou H.-B., Sheng S., Compton D.R., Kim Y., Joachimiak A., Sharma S., Carlson K.E., Katzenellenbogen B.S., Nettles K.W., Greene G.L., and Katzenellenbogen J.A. J. Med. Chem. 50 (2007) 399
24. Powell D., Gopalsamy A., Wang Y.D., Zhang N., Miranda M., McGinnis J.P., and Rabindran S.K. Bioorg. Med. Chem. Lett. 17 (2007) 1641
25. Shaaban M.R., Saleh T.S., and Farag A.M. Heterocycles 71 (2007) 1765
26. Fookes C.J.R., Pham T.Q., Mattner F., Greguric I., Loc'h C., Liu X., Berghofer P., Shepherd R., Gregoire M.-C., and Katsifis A. J. Med. Chem. 51 (2008) 3700
27. Farag A.M., Mayhoub A.S., Barakat S.E., and Bayomi A.H. Bioorg. Med. Chem. 16 (2008) 4569
28. El Agamey A.G.A., El-Sakka I., El-Shahat Z., and Elnagdi M.H. Arch. Pharm. 317 (1984) 289
29. Ivanov C. Chem. Ber. 87 (1954) 1600
30. Sezer O., and Anac O. Helv. Chim. Acta 77 (1994) 2323
31. Wright S.W., Harris R.R., Kerr J.S., Green A.M., Pinto D.J., Bruin E.M., Collins R.J., Dorow R.L., Mantegna L.R., Sherk S.R., Covington M.B., Nurnberg S.A., Welch P.K., Nelson M.J., and Magolda R.L. J. Med. Chem. 35 (1992) 4061
32. Mustazza C., Maria R., Del G., Borioni A., and Gatta F. J. Heterocycl. Chem. 38 (2001) 1119
33. Westaway S.M., Thompson M., Rami H.K., Stemp G., Trouw L.S., Mitchell D.J., Seal J.T., Medhurst S.J., Lappin S.C., Biggs J., Wright J., Arpino S., Jerman J.C., Cryan J.E., Holland V., Winborn K.Y., Coleman T., Stevens A.J., Davis J.B., and Gunthorpe M.J. Bioorg. Med. Chem. Lett. 18 (2008) 5609
34. For NMR data of 1, see the Supplementary data.
35. In addition, these β-ketoaldehydes are usually difficult to handle compared with β-enaminoketones.
36. CCDC 741294 contains the supplementary crystallographic data for compound 1n. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via ww.ccdc.cam.ac.uk/data_request/cif.
37. Compound 1p was prepared by mCPBA oxidation of compound 1o.
38. For the full in vitro data, see the Supplementary data.