The N4 nitrogen of pirenzepine is responsible for selective binding of the m1 subtype human muscarinic receptor

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 7, 1996, Pages 785-788

  Murgolo, Nicholas J ^a   Kozlowski, Joseph ^a   Tice, Melissa A B ^a   Hollinger, Frank P ^a   Brown, Joan E ^a   Zhou, Guowei ^a   Taylor, Lisa A ^a   McQuade, Robert D ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MUSCARINIC M1 RECEPTOR; MUSCARINIC M2 RECEPTOR; PIRENZEPINE; PIRENZEPINE DERIVATIVE; QUINUCLIDINYL BENZILATE; RECEPTOR SUBTYPE; SCH 55112; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BINDING SITE; CHO CELL; CONTROLLED STUDY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; HUMAN; MOLECULAR MODEL; MUTATION; NONHUMAN;

ANIMALIA;

EID: 0029922380     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00107-2     Document Type: Article

References (25)

1. McKinney, M.; Coyle, J. T. Mayo Clin. Proc. 1991, 66, 1225.
2. Grimm, U.; Moser, U.; Mutschler, E.; Lambrecht, G. Pharmazie 1994, 49, 711.
3. Doods, H. N.; Quiron, R.; Mihm, G.; Engel, W.; Rudolf, K.; Entzroth, M.; Schiavi, G. B.; Ladinsky, H.; Bechtel, W. D.; Ensinger, H. A.; Mendia, K. D.; Eberlein, W. Life Sci. 1993, 52, 497.
4. Hammer, R.; Berrie, C. P.; Birdsall, N. J. M.; Burgen, A. S. W.; Hulme, E. C. Nature 1980, 283, 90.
5. Peralta, E. G.; Ashkenazi, A.; Winslow, J. W.; Smith, D. H.; Ramachandran, J.; Capon, D. J. EMBO J., 1987, 6, 3923.
6. Bonner, T. I.; Young, A. C.; Brann, M. R.; Buckley, N. J.; Neuron 1988, 1, 403.
7. Engel, W. E.; Eberlein, W. G.; Mihm, G.; Hammer, R.; Trummlitz, G. J. Med. Chem. 1989, 32, 1718.
8. Munson, P. J.; Rodbard, D. Anal. Biochem. 1980, 107, 220.
9. McPherson, G. A. Comput. Programs Biomed. 1983, 17, 107.
10. Fraser, C. M.; Wang, C.-D.; Robinson, D. A.; Gocayne, J. D.; Venter, J. C. Mol Pharm. 1992, 262, 173.
11. Bluml, K.; Mutschler, E.; Wess, J. J. Biol. Chem. 1994, 269, 18870.
12. Drubbish, V.; Lameh, J.; Philip, M.; Sharma, Y. K.; Sadee, W. Pharm. Res. 1992, 9, 1644.
13. Matsui, H.; Lazareno, S.; Birdsall, N. J. M. Molec. Pharm. 1995, 47, 88.
14. Kontoyianni, M.; Lybrand, T. P.; Perspectives Drug Disc. Des. 1993, 1, 291.
15. Trumpp-Kallmeyer, S.; Hoflack, J.; Bruinvels, A.; Hibert, M.; J. Med. Chem. 1992, 35, 3448.
16. Nordvall, G.; Hacksell, U. J. Med. Chem. 1993, 36, 967.
17. Fanelli, F.; Menziana, M. C.; Carotti, A.; DeBenedetti, P. G. Bioorg. Med. Chem. 1994, 2, 195.
18. Kerckhoff, H.; Holtje, H.-D. Pharmazie 1994, 49, 566.
19. Fanelli, F.; Menziana, M. C.; DeBenedetti, P. G. Protein Eng. 1995, 8, 557.
20. Homology v. 2.3 was used for model generation. After ligand docking, models were refined for 500 steps by Molecular Mechanics Minimization with Discover v. 2.95.
21. Catalyst v. 2.1 was used to generate the conformational ensemble using the following conditions: 255 maximum number of conformers, a 20 Kcal/mol energy window, the CHARMM forcefield, the BEST conformer generation algorithm. Under these conditions an ensemble of 57 conformers was generated.
22. Smellie, A.; Teig, S. L.; Towbin, P. J. Comp. Chem. 1995, 16, 171.
23. Smellie, A., Teig, S. L.; Towbin, P. J. Chem. Inf. Comput. Sci. 1995, 35, 285.
24. Smellie, A.; Kahn, S. D.; Teig, S. J. Chem. Inf. Comput. Sci. 1995, 35, 295.
25. Liu, J.; Schoneberg, T.; vanRhee, M.; Wess, J. J. Biol. Chem. 1995, 270, 19532.