Comparison of different heterocyclic scaffolds as substrate analog PDE5 inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 17, 2005, Pages 3900-3907

  Haning, Helmut ^a   Niewöhner, Ulrich ^a   Schenke, Thomas ^a   Lampe, Thomas ^a   Hillisch, Alexander ^a   Bischoff, Erwin ^a  

^a BAYER PHARMA AG   (Germany)

Author keywords

Heterocycles; PDE5 inhibition

Indexed keywords

PHOSPHODIESTERASE V INHIBITOR; PYRAZOLOPYRIMIDINE DERIVATIVE; SILDENAFIL; SULFONAMIDE; TRIAZINE DERIVATIVE; VARDENAFIL; ZAPRINAST;

ARTICLE; COMPARATIVE STUDY; DRUG ACTIVITY; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; IN VIVO STUDY; STRUCTURE ACTIVITY RELATION;

3',5'-CYCLIC-GMP PHOSPHODIESTERASE; HETEROCYCLIC COMPOUNDS; INHIBITORY CONCENTRATION 50; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 23244434185     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.05.090     Document Type: Article

References (36)

1. G.B. Elion J. Med. Virol. Suppl. 1 1993 2
2. L. Schoenfeld, H. Ott, and G.R. Zahnd Helv. Med. Acta 32 1965 427
3. G.B. Elion Science 244 1989 41
4. H. Haning, U. Niewöhner, T. Schenke, M. Es-Sayed, G. Schmidt, T. Lampe, and E. Bischoff Bioorg. Med. Chem. Lett. 12 2002 865
5. B. Sung, K.Y. Hwang, Y.H. Jeon, J.I. Lee, Y.-S. Heo, J.H. Kim, J. Moon, J.M. Yoon, Y.-L. Hyun, E. Kim, S.J. Eum, S.-Y. Park, J.-O. Lee, T.G. Lee, S. Ro, and J.M. Cho Nature 425 2003 98
6. J.D. Corbin, A. Beasley, M.A. Blount, and S.H. Francis Neurochem. Int. 45 2004 859
7. Niewöhner, U.; Es-Sayed, M.; Haning, H.; Schenke, T.; Schlemmer, K.-H.; Keldenich, J.; Bischoff, E.; Perzborn, E.; Dembowsky, K.; Serno, P.; Nowakowski, M. PCT Int. Appl. 1999, WO 9924433; Chem. Abstr. 1999, 130, 352283.
8. Terrett, N. K. PCT Int. Appl. 1994, WO 9400453; Chem. Abstr. 1994, 121, 35196.
9. Niewoehner, U.; Bischoff, E.; Schuetz, H.; Perzborn, E.; Schramm, M Eur. Pat. Appl. 1996, EP 722943; Chem. Abstr. 1996, 125, 168009.
10. A. Miyashita, C. Iijima, T. Higashino, and H. Matsuda Heterocycles 31 1990 1309
11. M. Santagati, A. Santagati, M. Modica, and F. Russo Heterocycles 34 1992 923
12. B. Dumaitre, and N. Dodic J. Med. Chem. 39 1996 1635
13. Bell, A. S.; Terrett, N. K. PCT Int. Appl. 1993, WO 9307149, Chem. Abstr. 1993, 119, 95549.
14. Dumaitre, B. A.; Dodic, N. Eur. Pat. Appl. 1995, EP 636626, Chem. Abstr. 1995, 123, 228202.
15. Bacon, E. R.; Singh, B.; Lesher, G. Y U.S. Pat. Appl. 1994, US 5294612, Chem. Abstr. 1994, 121, 205376.
16. J.A. Markwalder, M.R. Arnone, P.A. Benfield, M. Boisclair, C.R. Burton, C.-H. Chang, S.S. Cox, P.M. Czerniak, C.L. Dean, D. Doleniak, R. Grafstrom, B.A. Harrison, R.F. Kaltenbach III, D.A. Nugiel, K.A. Rossi, S.R. Sherk, L.M. Sisk, P. Stouten, G.L. Trainor, P. Worland, and S.P. Seitz J. Med. Chem. 47 2004 5894
17. N.K. Terrett, A.S. Bell, D. Brown, and P. Ellis Bioorg. Med. Chem. Lett. 6 1996 1819
18. Bell, A. S.; Brown, D.; Terrett, N. K. Eur. Pat. Appl. 1992, EP 463756, Chem. Abstr. 1992, 116, 255626.
19. In the meantime the sildenafil scaffold 5-(2-ethoxyphenyl)-1-methyl-3- propyl-1,6-dihydro-7H-pyrazolo[4,3-d]-pyrimidin-7-one is commercially available.
20. B. Golankiewicz, P. Januszczyk, S. Ikeda, J. Balzarini, and E. De Clercq J. Med. Chem. 38 1995 3558
21. B. Golankiewicz, J.B. Holtwick, B.N. Holmes, E.N. Duesler, and N.J. Leonard J. Org. Chem. 44 1979 1740
22. J.B. Holtwick, B. Golankiewicz, B.N. Holmes, and N.J. Leonard J. Org. Chem. 44 1979 3835
23. Niewoehner, U.; Haning, H.; Lampe, T.; Es-Sayed, M.; Schmidt, G.; Bischoff, E.; Dembowsky, K.; Perzborn, E.; Schlemmer, K.-H. PCT Int. Appl. 2001, WO 01047928, Chem. Abstr. 2001, 135, 92657.
24. Inoue, H.; Murafuji, H.; Hayashi, Y. PCT Int. Appl. 2004, WO 04111053, Chem. Abstr. 2004, 142, 74617.
25. S. Laurent, M. Barbieux-Flammang, Y. Van Haverbeke, R. Flammang, and C. Wentrup Bull. Soc. Chim. Belg. 103 1994 181
26. Niewoehner, U.; Haning, H.; Lampe, T.; Es-Sayed, M.; Schmidt, G.; Bischoff, E.; Dembowsky, K.; Perzborn, E.; Schlemmer, K.-H. PCT Int. Appl. 2001, WO 01047934, Chem. Abstr. 2001, 135, 76888.
27. K. Gewald, P. Bellmann, and H.J. Jaensch Liebigs Ann. Chem. 10 1980 1623
28. C.A. Lovelette J. Heterocyclic Chem. 16 1979 555
29. K. Ramasamy, B.G. Ugarkar, P.A. McKernan, R.K. Robins, and G.R. Revankar J. Med. Chem. 29 1986 2231 2235
30. Niewoehner, U.; Haning, H.; Lampe, T.; Es-Sayed, M.; Schmidt, G.; Bischoff, E.; Dembowsky, K.; Perzborn, E.; Schlemmer, K.-H. PCT Int. Appl. 2001, WO 01047929, Chem. Abstr. 2001, 135, 92658.
31. 50 data refer to isolated human PDE5 from platelets and isolated bovine PDE1 unless otherwise noted.
32. E. Bischoff, and K. Schneider Int. J. Impotence Res. 13 2001 230
33. C.D. Boyle, R. Xu, T. Asberom, S. Chackalamannil, J.W. Clader, W.J. Greenlee, H. Guzik, Y. Hu, Z. Hu, C.M. Lankin, D.A. Pissarnitski, A.W. Stamford, Y. Wang, J. Skell, S. Kurowski, S. Vemulapalli, J. Palamanda, M. Chintala, P. Wu, J. Myers, and P. Wang Bioorg. Med. Chem. Lett. 15 2005 2365
34. K.Y. Zhang, G.L. Card, Y. Suzuki, D.R. Artis, D. Fong, S. Gillette, D. Hsieh, J. Neiman, B.L. West, C. Zhang, M.V. Milburn, S.H. Kim, J. Schlessinger, and G. Bollag Mol. Cell 15 2004 279
35. G.L. Card, B.P. England, Y. Suzuki, D. Fong, B. Powell, B. Lee, C. Luu, M. Tabrizizad, S. Gillette, P.N. Ibrahim, D.R. Artis, G. Bollag, M.V. Milburn, S.-H. Kim, J. Schlessinger, and K.Y.J. Zhang Structure 12 2004 2233
36. 2.