4710
V. Alikhani et al. / Bioorg. Med. Chem. Lett. 14 (2004) 4705–4710
chronic obstructive pulmonary disease. National Heart
lung and Blood Institute, Bethesda, 2000.
3. Matthys, H. Respiration 2001, 68, 432.
4. Johnson, M. Med. Res. Rev. 1995, 15, 225.
5. Anon Expert Opin. Ther. Pat. 2003, 13, 273.
6. Coleman, R. A.; Johnson, M.; Nials, A. T.; Vardey, C. J.
Trends Pharmacol. Sci. 1996, 17, 234.
´
7. Anderson, G. P.; Linden, A.; Rabe, K. F. Eur. Respir. J.
1994, 7, 569.
8. Lewell, X. Q. DrugDes. Discovery 1992, 9, 29.
9. Ochsner, M.; Jaekel, K.; Mutz, M.; Anderson, G. P.;
John, E. Eur. J. Med. Chem. 1994, 34, 451.
10. (a) Teschemacher, A.; Lemoine, H. J. Pharmacol. Exp.
18. (a) Furse, K. E.; Lybrand, T. P. J. Med. Chem. 2003, 46,
4450; (b) Isogaya, M.; Sugimoto, Y.; Tanimura, R.;
Tanaka, R.; Kikkawa, H.; Nagao, T.; Kurose, H. Mol.
Pharmacol. 1999, 56, 875; (c) Isogaya, M.; Yamagiwa, Y.;
Fujita, S.; Sugimoto, Y.; Nagao, T.; Kurose, H. Mol.
Pharmacol. 1998, 54, 616; (d) Kikkawa, H.; Isogaya, M.;
Nagao, T.; Kurose, H. Mol. Pharmacol. 1998, 53, 128.
19. Hett, R.; Fang, Q. K.; Gao, Y.; Hong, Y.; Butler, H. T.;
Nie, X.; Wald, S. A. Tetrahedron Lett. 1997, 38, 1125.
20. (a) Waldeck, B. Chirality 1993, 5, 350; (b) Trofast, J.;
¨
Osterberg, K.; Ka¨llstro¨m, B.-L.; Waldeck, B. Chirality
1991, 3, 443; (c) Murase, K.; Mase, T.; Ida, H.; Takahashi,
K.; Murakami, M. Chem. Pharm. Bull. 1978, 26, 1123.
21. Ki values were determined by the displacement of 3H
CGP12177 from the human b2-adrenoceptor expressed in
insect Sf21 membranes.
´
Ther. 1999, 288, 1084; (b) Bergendal, A.; Linden, A.;
Skoogh, B. E.; Gerspacher, M.; Anderson, G. P.; Lo¨fdahl,
C. G. Br. J. Pharmacol. 1996, 117, 1009.
11. Austin, R. P.; Barton, P.; Bonnert, R. V.; Brown, R. C.;
Cage, P. A.; Cheshire, D. R.; Davis, A. M.; Dougall, I. G.;
Ince, F.; Pairaudeau, G.; Young, A. J. Med. Chem. 2003,
46, 3210.
22. Nials, A. T.; Sumner, M. J.; Johnson, M.; Coleman, R. A.
J. Pharmacol. 1993, 108, 507.
23. Calculated logD7.4 values were generated using ACD
cLogD version 7.06 software.
12. Green, S. A.; Rathz, D. A.; Schuster, A. J.; Liggett, S. B.
Eur. J. Pharmacol. 2001, 421, 141.
24. Malcolmson, R. J.; Embleton, J. K. Pharm. Sci. Tech.
Today 1998, 1, 394.
13. Green, S. A.; Spasoff, A. P.; Coleman, R. A.; Johnson, M.;
Liggett, S. B. J. Biol. Chem. 1996, 271, 24029.
14. Waldeck, B. Eur. J. Pharmacol. 2002, 445, 1.
15. Strader, C. D.; Candelore, M. R.; Rands, E.; Hill, W. S.;
Dixon, R. A. F. J. Biol. Chem. 1988, 263, 10267.
16. Strader, C. D.; Candelore, M. R.; Hill, W. S.; Sigal, I. S.;
Dixon, R. A. F. J. Biol. Chem. 1989, 264, 13572.
17. Wieland, K.; Zuurmond, H. M.; Krasel, C.; IJzerman, A.
P.; Lohse, M. J. Proc. Natl. Acad. Sci. U.S.A. 1996, 93,
9726.
25. logD7.4 values were measured by potentiometric titration,
using a GlpKa instrument from Sirius Analytical Instru-
ments (Forest Row, UK).
26. logKIAM values were determined from HPLC retention
times, using a 10·3mm IAM fast screen mini column
(Regis speciality columns) with isocratic eluent;
1mLminꢀ1, 85% mixed phosphate pH7.4 buffer, 15%
acetonitrile and UV detection at 230nm.
27. Taillardat-Bertschinger, A.; Carrupt, P. A.; Barbato, F.;
Testa, B. J. Org. Chem. 2003, 46, 655.