Pyrrolooctahydroisoquinolines as potent and selective δ opioid receptor ligands: Sar analysis and docking studies

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 23, 1997, Pages 2967-2972

  Dondio, Giulio ^a   Ronzoni, Silvano ^a   Petrillo, Paola ^a   DesJarlais, Renee L ^b   Raveglia, Luca F ^a  

^a SmithKline Beecham   (Italy)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3,4,4A,5,12,12AALPHA OCTAHYDRO 4AALPHA (3 HYDROXYPHENYL) 2 METHYLQUINOLINO[2,3 G]ISOQUINOLINE; DELTA OPIATE RECEPTOR; LIGAND; PYRROLO[2,1 A]ISOQUINOLINE DERIVATIVE; SB 219825; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DIELECTRIC CONSTANT; DRUG RECEPTOR BINDING; ELECTRICITY; MOUSE; NONHUMAN; QUANTUM MECHANICS; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

EID: 0030696975     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)10119-6     Document Type: Article

References (31)

1. Pasternak, G.W. The Opiate Receptors (The Humana Press, Clifton, New Jersey), 1988.
2. (a) Wang, J.B.; Johnson, P.S.; Persico, A.M.; Hawkins, A.L.; Griffin, C.A.; Uhl, G.R. FEBS Lett. 1994, 338, 217.
3. (b) Mansson, E.; Bare, L.; Yang, D. Biochem. Biophys. Res. Commun. 1994, 202, 1431.
4. (c) Knapp, R.J.; Malatynska, E.; Fang, L.; Li, X.; Babin, E.; Nguyen, M.; Santoro, G.; Varga, E.V.; Hruby, V.J.; Roeske, W.R.; Yamamura, H.I. Life Sci. 1994, 54, PL463.
5. Olson, G.A.; Olson, R.D.; Kastin, A.J. Peptides 1992, 13, 1247.
6. Giardina, G.; Clarke, G.D.; Grugni, M.; Sbacchi, M.; Vecchietti, V. Il Farmaco 1995, 50, 405.
7. (a) Cheng, P.Y.; Wu, D.; Decena, J.; Soong, Y.; McCabe, S.; Szeto, H.H. Eur. J. Pharmacol. 1993, 230, 85.
8. (b) Cowan, A.; Zhu, X.Z.; Mosberg, H.I.; Omnaas, J.R.; Porreca, F. J. Pharmacol. Exp. Ther. 1988, 246, 950.
9. (c) Porreca, F.; Mosberg, H.I.; Hurst, R.; Hruby, V.J.; Burks, T.F. Life Sci. 1983, 33, 457.
10. (d) Galligan, J.J.; Mosberg, H.I.; Hurst, R.; Hruby, V.J.; Burks, T.F. J. Pharmacol. Exp. Ther. 1984, 229, 641.
11. (e) Sheldon, R.J.; Riviere, P.J.M.; Malarchik, M.E.; Mosberg, H.I.; Burks, T.F.; Porreca, F. J. Pharmacol. Exp. Ther. 1990, 253, 144.
12. Portoghese, P.S.; Sultana, M.; Takemori, A.E. J. Med. Chem. 1990, 33, 1714.
13. (a) Dondio, G.; Clarke, G.D.; Giardina, G.; Petrillo, P.; Rapalli, L.; Ronzoni, S.; Vecchietti, V. Regulatory Pep. 1994, 21, 43.
14. (b) Dondio, G.; Clarke, G.D.; Giardina, G.; Petrillo, P.; Petrone, G.; Ronzoni, S.; Visentin, L.; Vecchietti, V. Analgesia 1995, I:4-6, 394.
15. Calderon, S.N.; Rothman, R.B.; Porreca, F.; Flippen-Anderson, J.L.; McNutt, R.W.; Xu, H.; Smith, L.E., Bilsky, E.J.; Davis, P.; Rice, K.C. J. Med. Chem. 1994, 37, 2125.
16. (a) Dondio, G.; Ronzoni, S. International Patent Application WO95/04734 (16.02.95); Chem. Abstr. 122, 314563j.
17. (a) Dondio, G.; Ronzoni, S. International Patent Application WO95/04734 (16.02.95); Chem. Abstr. 122, 314563j.
18. (b) Dondio, G.; Ronzoni, S.; Eggleston, D.; Artico, M.; Petrillo, P.; Petrone, P.; Visentin, L.; Farina, C.; Vecchietti, V.; Clarke, G.D. J. Med. Chem., in press.
19. 10) Products 2-6a and 4b were synthesised according to the methods described in ref. 9 (a) and 9 (b).
20. 3H]-U69,593 (k) in mouse brain homogenates, using the methods described in ref. 9 (b).
21. Judd, D.B.; Brown, D.S.; Lloyd, J.E.; McElroy, A.B.; Scopes, D.I.C.; Birch, P.J.; Hayes, A.G.; Sheehan, M.J. J. Med. Chem. 1992, 35, 48.
22. Henderson, R.; Baldwin, J.; Ceska, T.H.; Zemlin, F.; Beckmann, E.; Downing, K. J. Mol. Biol. 1990, 213, 899.
23. Trumpp-Kallmeyer, S.; Hoflack, J.; Bruinvels, A.; Hibert, M. J. Med. Chem. 1992, 35, 3448.
24. Weiner, S.G.; Kollman, P.A.; Case, D.A.; Singh, U.C.; Ghio, C.; Alagona, G.; Profeta, S., Jr.; Weiner, P. J. Am. Chem. Soc. 1984, 106, 765.
25. Pearlman, D.A.; Case, D.A.; Caldwell, J.W., Ross, W.S.; Cheatham III, T.E.; Ferguson, D.M.; Seibel, G.L.; Singh, U.C.; Weiner, P.K.; Kollman, P.A.; AMBER 4.1, University of California, San Francisco, 1995.
26. The minimisation protocol consisted of 2000 steps of minimisation using a dielectric constant of 80 and constraining the backbone atoms to their starting positions, 2000 steps without constraints using a dielectric constant of 80 and, finally, 2000 steps without constraints using a dielectric constant of 10. This protocol was designed to remove any unfavourable van der Waals interactions without allowing the seven helices to collapse together and without being overly dominated by electrostatic interactions. A cut-off of 8 Å was used.
27. Befort, K.; Tabbara, L.; Bausch, S.; Chavkin, C.; Evans, C.; Kieffer, B. Mol Pharmacol. 1996, 49, 216.
28. Surratt, C.K.; Johnson, P.S; Moriwaki, A.; Seidleck, B.K.; Blaschak. C.J.; Wang, J.B.; Uhl, G.R. J. Biol. Chem. 1994, 269, 20548.
29. Metzger, T.G.; Paterlini, M.G.; Portoghese, P.S.; Ferguson, D.M. Neurochem. Res. 1996, 21, 1287.
30. Valiquette, M.; Vu, H.K.; Yue, S.Y.; Wahlestedt, C.; Walker, P. J. Biol. Chem. 1996, 271, 18789.
31. Molecular graphics images were produced using the MidasPlus program from the Computer Graphics Laboratory, University of California, San Francisco (supported by NIH RR-01081).